Title: Blood Transfusion
Author: Keynes, Geoffrey
Language: English
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BLOOD TRANSFUSION



  OXFORD MEDICAL PUBLICATIONS

  BLOOD TRANSFUSION

  BY
  GEOFFREY KEYNES
  M.A., M.D. CANTAB., F.R.C.S. ENG.
  SECOND ASSISTANT, SURGICAL PROFESSORIAL UNIT
  ST. BARTHOLOMEW’S HOSPITAL


  LONDON
  HENRY FROWDE _AND_ HODDER & STOUGHTON
  THE _LANCET_ BUILDING
  1 BEDFORD STREET, STRAND, W.C.2



  _First published in 1922_


  PRINTED IN GREAT BRITAIN
  BY HAZELL, WATSON AND VINEY, LD.,
  LONDON AND AYLESBURY.



PREFACE


Blood transfusion is of rapidly growing importance in modern
therapeutics, yet the subject has only been represented in
the medical literature of this country hitherto by isolated
communications concerning special points. The present work seeks to
give a connected account of the whole subject and of the problems
arising from it, together with practical instructions for performing
transfusions by an efficient and simple method.

I am indebted for helpful criticisms and suggestions to Professor A.
V. Hill, F.R.S., of Manchester University. Dr. J. H. Drysdale has
kindly allowed me to use the records of three cases of pernicious
anæmia treated in his wards at St. Bartholomew’s Hospital. Dr. Joekes
has permitted me to refer to some of his own observations concerning
abnormal serum reactions. Dr. R. M. Janes has given me some account
of the important work recently done by Dr. Bruce Robertson and
himself at the Hospital for Sick Children, Toronto.

The Bibliography at the end of the book makes no pretence of being
absolutely complete. It is, however, more extensive than any that has
yet been printed, and I believe that it contains references to nearly
all the contributions of present importance published up to the date
of going to press. Numbers referring to the Bibliography have been
inserted in the text only where no name is given to the authority
quoted.

  GEOFFREY KEYNES.

  86, HARLEY STREET, W.1.
  _February 1922_.



  CONTENTS


      CHAPTER I
                                                       PAGE
  HISTORICAL SKETCH                                       1


      CHAPTER II

  INDICATIONS FOR BLOOD TRANSFUSION: HÆMORRHAGE
  AND SHOCK                                              19


      CHAPTER III

  INDICATIONS FOR BLOOD TRANSFUSION--_continued_:
  HÆMORRHAGIC DISEASES--BLOOD DISEASES--TOXÆMIAS         44


      CHAPTER IV

  DANGERS OF BLOOD TRANSFUSION                           67


      CHAPTER V

  PHYSIOLOGY AND PATHOLOGY OF BLOOD GROUPS               79


      CHAPTER VI

  THE CHOICE OF BLOOD DONOR                              97


      CHAPTER VII

  THE METHODS OF BLOOD TRANSFUSION                      108

  BIBLIOGRAPHY                                          137

  INDEX                                                 159



BLOOD TRANSFUSION



CHAPTER I

HISTORICAL SKETCH


From the earliest times the vital importance of blood to the human
system has been fully appreciated. It has been supposed to carry
in it some of the virtues, such as the youth and health, of its
possessor, and it has therefore been commonly regarded as a sacrifice
acceptable to the gods. References to blood in the Old Testament, in
classical authors, and, it is stated, in the writings of the ancient
Egyptians, refer rather to these mystical attributes than to any
definite transference of it from the veins of one animal to those
of another. One of the earliest references to actual transfusion of
blood that has been noticed is to be found in a work by Libavius of
Halle, published in 1615. The passage has been translated as follows:

“Let there be present a robust healthy youth full of lively blood.
Let there come one exhausted in strength, weak, enervated, scarcely
breathing. Let the master of the art have little tubes that can be
adapted one to the other; then let him open an artery of the healthy
one, insert the tube and secure it. Next let him incise the artery of
the patient and put into it the feminine tube. Now let him adapt the
two tubes to each other and the arterial blood of the healthy one,
warm and full of spirit, will leap into the sick one, and immediately
will bring him to the fountain of life, and will drive away all
languor.”

It may be assumed, however, that this was only an idea, and had
not yet been carried into practice. It was, indeed, unlikely that
any attempt to perform blood transfusion would be made until the
conception of the circulation of the blood had been promulgated, and
this in 1615 had not yet taken place.

William Harvey had been appointed physician to St. Bartholomew’s
Hospital in 1609, and already in 1616 as Lumleian lecturer had stated
his theory of the circulation, but not until its publication twelve
years later could it be generally known. His treatise entitled
_Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus_,
which appeared in 1628, may therefore be regarded as the point from
which blood transfusion first arose. It has often been stated in the
literature of the subject that the first transfusion was performed
in 1492, when the blood of three boys is supposed to have been
transfused into the veins of the aged Pope Innocent VIII.[1] This,
however, seems to have been a mis-statement of the facts. Actually a
Jewish physician prepared a draught for the Pope from the blood of
three boys, who were bled to death for the purpose.[2] The drinking
of blood was not a new idea; this particular incident is of no
special interest, and may now be allowed to sink into oblivion.

It is not until after the middle of the seventeenth century that
authentic references to blood transfusion are to be found. The first
is in the writings of Francesco Folli, a Florentine physician, who
claims to have demonstrated the operation of transfusion of blood on
August 13, 1654, to the Grand Duke Frederick II. There does not seem
to be any confirmation of this in the writings of others. A few years
later experimental work tending in the same direction was being done
in England, and the inception of this was due to the ingenious Sir
Christopher Wren, who in this connexion has not hitherto received
the recognition that is his due. Dr. Wren, as he was designated at
the time, was one of the most active members of the recently formed
Royal Society, and was responsible for many new experiments in
several sciences. It is clear from references in the _Philosophical
Transactions_ that his first experiments were done in 1659, and the
following statement is made by Dr. Thomas Sprat in his _History of
the Royal Society_, published in 1667:

“He was the first author of the Noble Anatomical Experiment of
Injecting Liquors into the Veins of Animals. An Experiment now
vulgarly known; but long since exhibited to the Meetings at Oxford,
and thence carried by some Germans, and published abroad. By this
Operation divers Creatures were immediately purg’d, vomited,
intoxicated, kill’d, or reviv’d according to the quality of the
Liquor injected: Hence arose many new Experiments, and chiefly that
of Transfusing Blood, which the Society has prosecuted in sundry
Instances, that will probably end in extraordinary Success” (p. 317).

Sir Christopher Wren did not actually carry out any transfusion
experiments on his own account. This was done by his friend, Richard
Lower, well known for his work on the anatomy of the heart, who
worked in the laboratory of Thomas Willis at Oxford. In these
experiments, some account of which was published in 1666, he used a
silver cannula for obtaining continuity between the artery of one
animal and the vein of another. Lower must therefore receive the
credit for having done the first transfusion actually performed in
England. In the following year other experiments were done by Dr.
Edmund King and Thomas Cox, both of whom recorded their experiences
in the _Philosophical Transactions_.

Meanwhile Wren’s work had become known in other countries, and it is
said that transfusion was performed in 1664 by Daniel of Leipsic,
who thus anticipated the work of Lower. However this may be, the
first transfusion done upon a human being was certainly carried out
in France by Jean Denys of Montpellier, physician to Louis XIV. This
is admitted in the _Philosophical Transactions_, but the following
statement in extenuation of English hesitancy is made:

“We readily grant, They were the first, we know off, that actually
thus improved the Experiment; but then they must give us leave to
inform them of this Truth, that the Philosophers in England had
practised it long agoe upon Man, if they had not been so tender in
hazarding the Life of Man (which they take so much pains for to
preserve and relieve), nor so scrupulous to incurre the Penalties of
the Law, which in England, is more strict and nice in case of this
concernment, than those of many other Nations are.”

Dr. Edmund King further asserts that “We have been ready for this
Experiment these six Months,” that is to say, since March, 1667.
Moral precedence must, however, give way to the actual, and it is
clear that Denys had snatched the laurels. A translation of a full
and interesting account of his earlier experiment upon animals
and his first two transfusions done upon men was published in the
_Philosophical Transactions_ for July 22, 1667. Of the first of these
he wrote as follows:

“On the 15 of this Moneth, we hapned upon a Youth aged between 15
and 16 years, who had for above two moneths bin tormented with a
contumacious and violent fever, which obliged his Physitians to bleed
him 20 times, in order to asswage the excessive heat.

“Before this disease, he was not observed to be of a lumpish dull
spirit, his memory was happy enough, and he seem’d chearful and
nimble enough in body; but since the violence of his fever, his
writ seem’d wholly sunk, his memory perfectly lost, and his body so
heavy and drowsie that he was not fit for any thing. I beheld him
fall asleep as he sate at dinner, as he was eating his Breakfast,
and in all occurrences where men seem most unlikely to sleep. If he
went to bed at nine of the clock in the Evening, he needed to be
wakened several times before he could be got to rise by nine the next
morning, and pass’d the rest of the day in an incredible stupidity.

“I attributed all these changes to the great evacuations of blood,
the Physitians had been oblig’d to make for saving his life, and I
perswaded myself that the little they had left him was extreamly
incrustated [? incrassated] by the ardour of the fever....
Accordingly my conjecture was confirmed by our opening one of his
Veins, for we beheld a blood so black and thick issue forth, that it
could hardly form itself into a thread to fall into the porringer.
We took about three ounces at five of the Clock in the morning, and
at the same time we brought a Lamb, whose Carotis Artery we had
prepar’d, out of which we immitted into the young man’s Vein, about
three times as much of its Arterial blood as he had emitted into the
Dish, and then having stopt the orifice of the Vein with a little
bolster, as is usual in other phlebotomies, we caus’d him to lie down
on his Bed, expecting the event; and as I askt him now and then how
he found himself, he told me that during the operation he had felt a
very great heat along his Arm, and since perceiv’d himself much eased
of a pain in his side, which he had gotten the evening before by
falling down a pair of staires of ten steps; about ten of the clock
he was minded to rise, and being I observed him cheerful enough, I
did not oppose it; and for the rest of the day, he spent it with much
more liveliness than ordinary; eat his Meals very well, and shewed a
clear and smiling countenance.... He grows fat visibly, and in brief,
is a subject of amazement to all those that know him, and dwell with
him.”

This boy had been transfused for therapeutic purposes; the second
transfusion performed by Denys was done upon an older man “having
no considerable indisposition,” and was purely experimental. About
twenty ounces of lamb’s blood are stated to have been transfused,
but the procedure was without any ill effect, and it may be doubted
whether the man received as much as this.

In the succeeding number of the _Philosophical Transactions_, October
21, 1667, the remarks of another French experimenter, Gaspar de
Gurye, are quoted. These are of considerable interest, as they
contain the first warning of the dangers attending the administration
of incompatible blood. De Gurye affirms “that an expert Acquaintance
of his, transfusing a great quantity of blood into several Doggs,
observed alwayes, that the Receiving Doggs pissed Blood.”

Other cases were subsequently recorded by Denys. In one he claims
to have cured a patient suffering from “an inveterate Phrenzy.” His
account of it is too long to be quoted here in full, but it is of
special interest in that it contains the first account of hæmolysis
and the attendant symptoms in man which follow the transfusion of
incompatible blood. The blood of a calf was used in this instance and
on two occasions; at the first transfusion only a small amount was
given, but at the second,

“the Patient must have received more than one whole pound. As this
second Transfusion was larger, so were the effects of it quicker
and more considerable. As soon as the blood began to enter into his
veins, he felt the like heat along his Arm and under his Arm-pits
which he had felt before. His pulse rose presently, and soon after
we observed a plentiful sweat all over his face. His pulse varied
extremely at this instant, and he complained of great pain in his
Kidneys, and that he was not well in his stomack, and that he was
ready to choak unless they gave him his liberty.

“Presently the Pipe was taken out that conveyed the blood into his
veins, and whilst we were closing the wound, he vomited store of
Bacon and Fat he had eaten half an hour before. He found himself
urged to Urine, and asked to go to stooll. He was soon made to lie
down, and after two good hours strainings to void divers liquors,
which disturbed his stomack, he fell asleep about 10 a Clock, and
slept all that night without awakening till next morning, was
Thursday, about 8 a Clock. When he awakened, he shewed a surprising
calmness, and a great presence of mind, in expressing all the pains
and a general lassitude he felt in all his limbs. He made a great
glass full of Urine, of a colour as black, as if it had been mixed
with the soot of Chimneys.”

The hæmoglobinuria, which was not at that time attributed to its
true cause, cleared up in the course of a few days, and the patient
appeared to be greatly benefited.

Although the first transfusion performed upon a human being was done
in France, similar experiments were shortly afterwards carried out in
England. The passage already quoted concerning the “sundry instances”
mentioned in Sprat’s _History of the Royal Society_ is amplified by
the diarist, Samuel Pepys, who witnessed the experiments on at least
one occasion. His first reference to the subject is under the date
November 14, 1666:

“Here [at the Pope’s Head] Dr. Croone told me, that, at the meeting
at Gresham College to-night, ... there was a pretty experiment of the
blood of one dogg let out, till he died, into the body of another on
one side, while all his own run out on the other side. The first died
upon the place, and the other very well, and likely to do well. This
did give occasion to many pretty wishes, as of the blood of a Quaker
to be let into an Archbishop, and such like; but, as Dr. Croone
says, may, if it takes, be of mighty use to man’s health, for the
amending of bad blood by borrowing from a better body.” (_Diary_, ed.
Wheatley, vi. p. 60.)

Two days later he reports:

“This noon I met with Mr. Hooke, and he tells me the dog which was
filled with another dog’s blood, at the College the other day, is
very well, and like to be so as ever, and doubts not its being found
of great use to men,--and so do Dr. Whistler, who dined with us at
the tavern.” (Ibid., p. 63.)

On November 28 there was further conversation at Gresham College to
the same effect (ibid., p. 79). In the following year the experiments
were taken a stage further, and Pepys refers again to them under the
date November 21, 1667:

“Among the rest they discourse of a man that is a little frantic,
that hath been a kind of minister, Dr. Wilkins saying that he hath
read for him in his church, that is poor and a debauched man, that
the College have hired for 20s. to have some of the blood of a sheep
let into his body; and it is to be done on Saturday next. They
purpose to let in about twelve ounces; which they compute, is what
will be let in in a minute’s time by a watch. They differ in the
opinion they have of the effects of it; some think it may have a good
effect upon him as a frantic man by cooling his blood, others that it
will not have any effect at all. But the man is a healthy man, and by
this means will be able to give an account what alteration, if any,
he do find in himself, and so may be usefull.” (_Diary_, vii. p. 195.)

On November 29 Pepys dined at a house of entertainment, and enjoyed
good company.

“But here, above all, I was pleased to see the person who had his
blood taken out. He speaks well, and did this day give the Society a
relation thereof in Latin, saying that he finds himself much better
since, and as a new man, but he is cracked a little in his head,
though he speaks very reasonably, and very well. He had but 20s.
for his suffering it, and is to have the same again tried upon him:
the first sound man that ever had it tried on him in England, and
but one that we hear of in France, which was a porter hired by the
virtuosos.”[3] (Ibid., p. 205.)

The subject of this experiment was Arthur Coga, an indigent Bachelor
of Divinity of Cambridge, aged about thirty-two. It is recorded in
the _Philosophical Transactions_ that the experiment was performed by
Richard Lower and Edmund King at Arundel House on November 23, 1667,
in the presence of many spectators, including several physicians.
Coga, when asked why he had not the blood of some other creature
transfused into him, rather than that of a sheep, replied: “Sanguis
ovis symbolicam quandam facultatem habet cum sanguine Christi, quia
Christus est agnus Dei.”[4] It was estimated that Coga received eight
or nine ounces of blood, but he seems to have felt no effects, good
or ill, and it is probable that he did not actually receive as much
as this.

These beginnings in England and France led to the more frequent use
of blood transfusion, but soon afterwards the operation fell into
disrepute. Disasters followed the transfusions, and the practice also
met with violent opposition on the ground that terrible results,
such as the growth of horns, would follow the transfusion of an
animal’s blood into a human being. In consequence of this they were
actually forbidden in France by the Supreme Court until the Faculté
of Paris should signify its approval, but the necessary permission
was not given. The “extraordinary success” predicted by Sprat and the
sanguine expectations of Pepys and his friends were destined not to
be fulfilled until a later age.

For more than a hundred years the possibilities of blood transfusion
were almost entirely neglected. There are some isolated references
to it in medical writings towards the end of the eighteenth century,
but of these it is only necessary to notice two. In 1792, at Eye in
Suffolk, blood from two lambs was transfused by a Dr. Russell into
a boy suffering from hydrophobia, and he claimed that the patient’s
recovery was to be attributed to the treatment. Soon afterwards
in 1796 Erasmus Darwin recommended transfusion for putrid fever,
cancer of the œsophagus, and in other cases of impaired nutrition.
He suggested that the blood should be transferred from donor to
recipient through goose quills connected by a short length of
chicken’s gut, which could be alternately allowed to fill from the
donor and emptied by pressure into the patient. This operation he
never actually performed.

[Illustration: Fig. 1.--BLUNDELL’S IMPELLOR

From _Researches Physiological and Pathological_, 1824]

A more general interest in the subject was revived in England by
the work of James Blundell, lecturer on physiology and midwifery at
St. Thomas’s and Guy’s Hospitals. He published in 1818 his earliest
paper on experimental transfusion with a special form of syringe
invented by himself. His first apparatus consisted of a funnel-shaped
receptacle for the blood, connected by a two-way tap with a syringe
from which the blood was injected through a tube and cannula into the
recipient. His experiments were performed upon dogs, and he began by
drawing blood from the femoral artery and re-injecting it into the
same animal through the femoral vein. He then conducted a long series
of investigations into the properties of blood, the effects of its
withdrawal, and the resuscitation of an exsanguinated animal. Soon he
had opportunities of transfusing patients with human blood, and the
results are recorded in his paper of 1824. His apparatus had by then
been elaborated, and an engraving of his _Impellor_, as he termed
it, is reproduced here. It consisted as before of a funnel-shaped
receptacle for the blood, but the syringe was now incorporated in
one side of the funnel, and contained a complicated system of spring
valves, which caused the blood to travel along the delivery tube when
the piston was pushed down. The Impellor was fixed to the back of a
chair in order to give it stability.

All the patients transfused by Blundell were either exceedingly
ill, or, judging from his description, already dead, so that his
results, considered statistically, were not favourable! Nevertheless,
he was not discouraged, and stated his “own persuasion to be that
transfusion by the syringe is a very feasible and useful operation,
and that, after undergoing the usual ordeal of neglect, opposition,
and ridicule, it will, hereafter, be admitted into general practice.
Whether mankind are to receive the first benefit of it, in this or
any future age, from British surgery, or that of foreign countries,
time, the discoverer of truth and falsehood, must determine.”
Blundell’s work has been described in some detail because, after the
experimental work of the seventeenth century, the year 1818 may be
taken to mark the real beginning of the clinical application of blood
transfusion.

The chief difficulty in the way of successful transfusion was, of
course, the obstacle introduced by the coagulation of the blood.
Bischoff in 1835 sought to overcome this by injecting defibrinated
blood, and that solution of the difficulty was adopted by many
operators, including Sir Thomas Smith, who, in 1873, used
defibrinated blood for transfusing a case of melæna neonatorum at
St. Bartholomew’s Hospital. The apparatus on this occasion consisted
of “a wire egg-beater, a hair sieve, a three-ounce glass aspirator
syringe, a fine blunt-ended aspirator cannula, a short piece of
india-rubber tubing with a brass nozzle at either end connecting the
syringe with the cannula, a tall narrow vessel standing in warm water
for defibrinating the blood, and a suitable vessel floated in warm
water to contain the defibrinated blood.” Others, too numerous to be
individually named, used the same method throughout the nineteenth
century and during the first ten years of the twentieth. Even in
1914 a method of using defibrinated blood was described by Moss. An
objection was raised in 1877 that it was dangerous to do this, owing
to the excess of fibrin ferment introduced with blood thus treated,
but this did not greatly discourage its use. Then, as now, one of the
chief uses of blood transfusion was found to be in the practice of
obstetrics. A series of 57 cases of this kind were reported by Martin
of Berlin in 1859, 43 of these having been successful. A further
series of cases was collected by Blasius in 1863. He was able to
report that of 116 transfusions performed during the previous forty
years, in 56 the results were satisfactory. These statistics did
not indicate a remarkable degree of success. Fatalities due to the
transfusion had occurred, attended by the symptoms which we have now
learned to associate with incompatibility of the transfused blood.
At that time, however, the deaths were believed to be due chiefly to
the introduction of air bubbles into the circulation, although it had
been shown experimentally by Blundell in 1818, and again by Oré in
1868, that small quantities, such as might be accidentally introduced
during a transfusion, produced no ill effects. Some explanation,
however, was required, and so air bubbles for a long time received
the blame.

[Illustration: Fig. 2.--MR. HIGGINSON’S TRANSFUSION INSTRUMENT

  A is a metallic cup, of 6-oz. capacity, to receive the supply of
  blood. B an outer casing, which will hold 5 oz. of hot water,
  introduced through an aperture at C. D is a passage leading into
  an elastic barrel, composed of vulcanized india-rubber, E, of
  which the capacity is 1 oz. F′ the exit for the blood into the
  injection-pipe G. At D and F there are ball-valves, capable of
  closing the upper openings when thrown up against them, but leaving
  the lower openings always free. The blood, or other fluid, poured
  into the cup A, has free power to run unobstructed through D, E, F;
  a small plug H is therefore provided to close the lower aperture
  F when necessary. The tube G is of vulcanized india-rubber, and
  terminates in a metal tube O for insertion into the vein. This
  diagram is one-half the actual size of the instrument.]

Although some of the early experiments on blood transfusion had
been done in England, and although its revival in the nineteenth
century was initiated in England, yet it is to be noticed that most
of the references to it up to 1874 are to be found in the works of
Continental writers. Nevertheless, an important modification was
introduced into the technique of the operation in 1857 by Higginson,
who applied the principle of a rubber syringe with ball-valves for
transferring the blood from the receptacle into which it was drawn,
to the vein of the recipient. This apparatus is illustrated here,
as it is of some interest in the history of medicine. Higginson’s
syringe is now used for a different purpose, but it was successfully
applied by its inventor in a series of seven cases which he duly
reported. One patient whom he transfused was suffering from extreme
weakness, which was attributed to the too protracted suckling of
twins. He gave her about twelve ounces of blood from a healthy female
servant, and a state of quietude followed her previous restlessness.
A few minutes later the patient was seized with a rather severe
rigor. It did not last long, but led to a state of reaction and
excitement, in which she sang a hymn in a loud voice. The final
result was good, and Higginson reports that in five of the seven
cases some benefit was to be attributed to the transfusions. Later
the same principle was used in America by Aveling and by Fryer about
the year 1874, and subsequently it was in that country that nearly
all the important advances in the science of blood transfusion were
made.

In 1873 an inquiry was carried out by the Obstetrical Society of
London into the merits of transfusion, the subject having been
brought to the Society’s notice by a report of a case by Aveling,
and an interesting summary of the evidence was prepared by Madge
in 1874. The results do not seem to have been very encouraging,
and transfusion was still regarded as a procedure that was only to
be used as a last resource. Even at this date the blood of other
animals was being used for transfusion, although the practice had
been discredited by Panum in 1863 and by others, and a series of
cases was reported by Hasse in 1873, in which lamb’s blood was given
for various conditions. Other cases were reported from Italy (3) and
Russia (101). Sentiment, if not science, seems to have suggested
that there was something repulsive in bringing a lamb into the sick
chamber and mixing animal with human blood, but it was remarked in a
discussion on the subject that “it was only taking lamb in another
form.”

After 1875, however, there was a decline in the amount of attention
given to transfusion which lasted for thirty years. This was
probably due in part to the increasing number of fatalities which
had followed the more general use of transfusion, but, as Peterson
suggests, it was also to be accounted for by the increasing use of
normal saline solution for intravenous injection in the treatment
of hæmorrhage. There was also a period during which the use of milk
was advocated for intravenous therapy (37, 279). Soon after the
beginning of the twentieth century transfusion received a fresh
impetus which has steadily gained force up to the present time. The
free use of cannulæ and syringes had always been hampered by the
coagulation of the blood, and it was clearly a great advance to be
able to perform a direct transfusion without the intervention of any
tube. This was made possible by great improvements in the surgery
of the blood-vessels, which were due in the first place to the work
of Murphy, published in 1897; they were carried still further by
others, such as Carrel and Guthrie, and culminated in the work of
Crile, who in 1907 put the technique of direct transfusion on a
securer basis than it had ever been before. His method is briefly
described in a later chapter of the present work. Meanwhile the chief
factor responsible for previous fatalities was being eliminated.
The presence of agglutinins and iso-agglutinins in the blood had
been detected by Landsteiner and by Shattock in 1901; in 1907 the
four blood groups into which human beings can be classified were
determined by Jansky and the work was repeated by Moss in 1910.

Simplification of the group tests soon followed, as is described
in another chapter. At the same time great improvements were made
in the use of syringes, paraffined tubes, and in anastomosis of
the blood-vessels. In this connexion one of the most notable
contributions was made by Curtis and David, who in 1911 introduced
the use of syringe transfusion through a two-armed tube coated on the
inside with paraffin. In 1913 indirect transfusion by means of the
paraffined vessel was introduced by Kimpton and Brown, and it was
now evident that blood transfusion was shortly to become a method of
treatment which would be without any very difficult technique, and
could therefore be more extensively applied.

The final advance was made in 1914, when the use of sodium citrate
as an anticoagulant was made possible by the work of Lewisohn in
America, of Hustin in Belgium, and of several others, who all arrived
independently, but almost simultaneously, at the same conclusion.
The use of an anticoagulant was no new idea. In 1858 the use of
small quantities of ammonia had been suggested by B. W. Richardson
in the _Guy’s Hospital Reports_, and in 1869 sodium phosphate was
used in four obstetrical cases by Braxton Hicks, who found that the
process was greatly facilitated thereby; but neither of these methods
came into general use. It had long been known that hirudin or leech
extract, and the salts of oxalic acid or of citric acid, could be
used as anticoagulants outside the body, but their supposed toxicity
had prevented their being used for transfusion. The proof that sodium
citrate was both efficient for this purpose and non-toxic in a
dilution that was still effective at once raised blood transfusion to
a wider sphere of usefulness than had been possible before. The first
transfusion of citrated blood was performed by Professor L. Agote of
Buenos Aires, on November 14, 1914, a date which is therefore of the
greatest importance in the history of blood transfusion. A method had
at last been discovered which approached the ideal, since it united
the four cardinal virtues of simplicity, certainty, safety, and
efficiency.

This great stride forward in the technique of blood transfusion
coincided so nearly with the beginning of the war that it seemed
almost as if foreknowledge of the necessity for it in treating war
wounds had stimulated research. Yet during the first two years
of the war almost nothing was known in the British Army of its
possibilities. I have no evidence that the French or German army
doctors were any better informed than ourselves. Some attempt was
made in 1916 to introduce the use of direct transfusion through
cannulæ, but the technique was too difficult and uncertain for the
stress of war conditions. It was not until 1917, when the British
Army Medical Corps was being steadily reinforced with officers from
the United States of America, that knowledge of blood transfusion
began to be spread through the Armies. A conspicuous part was borne
by Oswald Robertson in introducing the use of the citrate method,
and to him a very large number of men indirectly owe their lives.
In some armies the paraffined vessel of Kimpton and Brown remained
the favourite method, but to me the citrate method seemed the more
suitable, because of the certainty with which success could be
attained, and the same view was taken by many others. At the same
time the investigators appointed by the Medical Research Committee
attempted to elucidate the problems connected with hæmorrhage and
wound shock, and their results, as will be seen, served to confirm
the estimate already being formed of the value of blood transfusion.

In this way a large number of operators in this country became
familiar with the various methods, and transfusion has in consequence
been used increasingly in civilian practice since the war. It is
undoubtedly destined to figure still more largely in the therapeutics
of the future. Meanwhile the public mind is becoming gradually more
used to the idea, and the time is past when every transfusion is
deemed worthy of a sensational headline in a newspaper. Nevertheless,
at the end of the year 1920 the following advertisement appeared in
the personal columns of _The Times_:

  “Will any Doctor who knows method of treating cancer by transfusion
  of child’s blood kindly write Box --.”

So the wheel is come full circle, and the shade of Pope Innocent VIII
may well chuckle as he notes the small advance in popular knowledge
since the fifteenth century.



CHAPTER II

INDICATIONS FOR BLOOD TRANSFUSION


The indications for blood transfusion are gradually becoming more
numerous as experience of its effects accumulates, and there can be
no doubt that the value of transfusion as a therapeutic measure is
destined to become much more generally recognized than it is at the
present time. Lack of knowledge, together with an exaggerated idea of
the difficulties of the process, is the chief obstacle to its more
extended use. Time and the education of the rising generation will
provide the remedy for this.

The conditions for which blood transfusion may be used fall into four
well-defined groups. On the one hand are those characterized by an
acute anæmia, which demand the performance of a blood transfusion
as an emergency or life-saving operation; on the other hand are
those in which the anæmia is of slow onset, and is to be combated
by a single transfusion to tide the patient over an operation or a
critical period or by repeated transfusions in the hope of prolonging
the patient’s life if not of obtaining a cure. A third group includes
the hæmorrhagic diseases in which the transfusion is administered not
only to replace blood which has been lost, but also to bring about
cessation of the hæmorrhage. A fourth group includes cases of general
toxæmia, whether chemical or bacterial, in which the new blood is
given partly on account of its therapeutic properties, partly in
order to dilute the circulating toxins or to supply healthy red blood
cells to carry on the oxygenation of the tissues.

For the first and third of these groups blood transfusion is
now very firmly established as a method of treatment which is of
extraordinary value. For the second group it may be regarded as a
palliative to be given with circumspection. For the fourth group
administration of blood is still in the experimental stage.

In the present work each condition will be taken in turn and, as
far as possible, separately, though at the outset it has been found
undesirable to dissociate the two conditions, hæmorrhage and shock.
The present position of blood transfusion in relation to each
condition will be discussed; its limitations and the precautions to
be observed will be described.


HÆMORRHAGE AND SHOCK

Blood transfusion is pre-eminently the best form of treatment that
is known for the condition of acute anæmia following hæmorrhage to
whatever cause it may be due. Its good effects were seen by a number
of operators in many hundreds of exsanguinated patients during the
latter part of the war, and its value was then established upon
a secure foundation. It was unusual during the war to meet with
patients who were in danger of their lives from loss of blood alone
without the additional factor of traumatic shock, but such cases did
occur, and they are also to be met with in civil practice, as, for
instance, in attempted suicide by throat cutting, in gastric ulcer
with severe hæmatemesis, and in secondary hæmorrhage after operation.
The more typical condition following war wounds, hæmorrhage with
shock, will be faithfully reproduced in the victims of train or
street accidents, in patients who have undergone certain severe
operations, and in women suffering from post-partum hæmorrhage or a
ruptured ectopic gestation.

The signs and symptoms of acute anæmia will be familiar to most
readers. It is characterized by a peculiar greyness of the skin, by
extreme pallor of the mucous membranes, by a cold perspiration, by a
thready and rapid pulse which may exceed 140 beats to the minute,
and by extreme restlessness. The “amaurosis” of the text-books
is seldom met with, but in the last stages the patient becomes
semi-unconscious, the restlessness tends to disappear, the muscles
relax, and the respiration takes on a peculiar sighing character,
which is described as “air hunger,” and probably indicates exhaustion
of the respiratory centre. Meanwhile, if instruments are at hand,
additional signs may be recognized. The most important of these is a
fall in blood pressure. It has been stated that a systolic pressure
below 70 mm. of mercury is scarcely compatible with life, but this
is not in accordance with experience. It was common during the war
to meet with blood pressures below 45 mm., so low in fact that they
could not be measured with the ordinary apparatus that was available,
but many patients whose lives had reached even so low an ebb as
this were quickly restored by the administration of blood, provided
that the exsanguinated state had not lasted for too long a time.
If the medullary centres are damaged beyond recovery by inadequate
oxygenation lasting for several hours, then no treatment is of any
avail. But provided that it be given before this length of time
has elapsed, a blood transfusion may succeed in saving life at any
stage of the condition. Its efficacy is indeed only limited by the
actual cessation of the patient’s heart beats. I have successfully
treated a patient who before transfusion could only be described as
moribund. He was almost unconscious, absolutely blanched, and his
radial pulse imperceptible; his jaw was relaxed and his breathing had
become a series of fish-like gasps, such as are only associated with
imminent dissolution. His heart would certainly have ceased beating
within a few minutes, yet his condition improved so rapidly after
transfusion that an hour later it was possible, with the help of a
second transfusion, to amputate his leg above the knee. This patient
ultimately recovered, having been as near death as it is possible to
be and yet remain alive.

The results of a blood transfusion upon a patient suffering from
acute anæmia are, indeed, amongst the most dramatic effects to be
obtained in the whole range of surgery. Within a few minutes of its
commencement the whole aspect of the patient alters. His respiration
becomes deep and regular, his restlessness disappears, colour
returns to his face, his pulse rate falls, and he begins to take an
intelligent interest in his surroundings. These changes taking place
within a period of fifteen minutes may well strike an onlooker as
little short of miraculous. Shortly afterwards the patient may fall
into a natural sleep, a sure sign that the normal circulation has
been restored to the exhausted central nervous system.

In considering how much blood should ordinarily be given in the
treatment of acute anæmia, experience is a safer guide than any
theoretical considerations. Nevertheless, it is worth while to
inquire briefly into the experimental and theoretical basis upon
which the treatment of acute anæmia rests. It is difficult to
estimate accurately the total quantity of blood in the body of an
adult, but it has been variously stated by physiologists to be
from a twentieth to a tenth part of the body weight, or, in liquid
measure, from 3 to 6 litres (approximately 5 to 10 pints). This
has been estimated in several ways, the results of which show some
discrepancy. A figure approaching the higher one was obtained long
ago by the direct method of washing out the blood from the bodies
of executed criminals. Recently it has been claimed by Haldane that
these determinations were inaccurate; by means of his carbon monoxide
method, with the details of which we are not concerned here, he has
estimated that the blood volume is but one-twentieth of the body
weight, or in very stout persons is even as low as one-thirtieth.
Still more recently Haldane’s estimation has been challenged in
its turn by observers who have injected a dye into the circulation
and have then determined its degree of concentration in the blood
by means of colorimetric comparisons. It is evident that if the
dilution which occurs when a known quantity of dye is injected can
be accurately estimated, then the total volume of circulating fluid
can be calculated. This method could not be used until a non-toxic,
non-diffusable dye had been discovered, but it was found in 1915 that
“vital red” fulfilled these requirements (143). The results obtained
in this way show that those originally given by the direct method
were substantially correct. The blood volume was found to vary from
1/13 to 1/10·5 of the body weight; on the average it amounted to
5,350 cc., or 85 cc. per kilogram of body weight. These observations
have been in their turn criticized (114), but only to the extent
of reducing the amount by 1/10. It may therefore be assumed that,
according to the most recent work, the blood volume is from 5 to 6
litres, or, approximately, 8 to 10 pints.

It is a still more difficult matter for obvious reasons to estimate
how much blood a man can lose and yet remain alive. This will depend
partly on the power of physiological accommodation possessed by the
individual in his vaso-motor system and tissue fluids and partly
on the rapidity with which the bleeding takes place. Clinical
observations have shown that after a moderate hæmorrhage, such as
the withdrawal of 800 cc. of blood from a donor, the blood volume
may be restored to normal within an hour. If, on the other hand, the
hæmorrhage is excessive, a condition results in which the normal
process of rapid restoration of volume fails, and the circulation
remains in a dangerously depleted condition. The heart attempts to
keep the blood pressure at an adequate level by an increase in its
rate, but it is in effect attempting to circulate a small volume of
fluid in a vascular system which has become too big for it. Imperfect
oxygenation of the medullary and cerebral centres with exhaustion of
the heart results, and this is accompanied by all the symptoms of
anæmia which have been already described.

If the initial hæmorrhage be very rapid, death may result almost at
once, since the physiological processes may have no time to act. On
the other hand, a rapid hæmorrhage may under certain circumstances
save the patient’s life, for the immediate syncope which results
produces so great a fall in the blood pressure that hæmorrhage almost
ceases and a clot may form in the lumen of the divided vessel. If the
hæmorrhage be more gradual, the physiological compensation may at
first be adequate to maintain the blood volume, but finally a point
is reached at which this process fails and the patient then passes
into the condition of acute anæmia.

The actual amount of blood therefore that must be lost to be
fatal will vary according to circumstances. Experience shows that
hæmorrhage may take place into the peritoneal or pleural cavities
to the extent of two litres or even more, and it may be stated as a
rough guess that 2·5 litres, that is to say, even as much as almost
half the total blood volume, may be lost without immediate death
resulting. This degree of depletion could not, however, be endured
for long. A series of clinical observations made by Keith by the
vital-red method upon the blood volume in soldiers suffering from the
combined effects of hæmorrhage and wound shock showed that in the
most serious cases the volume was below 65 per cent. of the normal,
frequently even between 50 and 60 per cent. Serious symptoms followed
a reduction to between 65 and 75 per cent. In patients without
distressing symptoms the volume was never below 75 per cent. of the
normal. There is direct evidence, therefore, that those patients who
are most in need of treatment, such as a transfusion of blood, will
probably have lost from 25 to 50 per cent. of their blood volume,
that is to say, 1·5 to 3 litres in amount, and will need from 750 cc.
to 1·5 litres to restore them to, or near to, the 75 per cent. level
at which the compensatory processes can begin to regain their power.

It is thus possible to arrive at a theoretical basis on which an idea
can be formed of the amount of blood that should be given in acute
anæmia. Practical experience is in agreement with the theory, and it
will now be easier to understand how it is that in treating acute
anæmia no attempt need be made to replace the whole amount of blood
that has been lost, or indeed anything approaching it. In an extreme
case 2 to 3 litres of blood will have been lost and 1 litre or more
will be needed to restore the blood volume to approximately 75 per
cent. of the normal. A case of this sort, however, is fortunately
not often to be met. One has already been described on page 21;
this patient received altogether nearly 1,600 cc. of blood in two
transfusions, and 1,000 cc. of normal saline were given in addition.

In most cases of severe hæmorrhage the patient has probably not lost
more than 1,400 to 1,800 cc. of blood, and 600 to 800 cc. will be
enough to restore the balance of the circulation. This is in practice
the amount of blood that is commonly administered, and it is well
within the limits of what a single blood donor can afford to lose.
If a more definite standard be required, it may be laid down that
in a single transfusion for acute anæmia 750 cc. of blood should
be given. If, in an exceptional case, more than this is needed, a
second transfusion should be performed with a similar amount taken
from another donor. Sometimes it may happen that a patient already
_in extremis_ from loss of blood, needs a severe operation; in such
a case a second transfusion may be given with great advantage at
the conclusion of the operation. The first transfusion will restore
the patient sufficiently to render the performance of an operation
possible; the second will combat the additional shock and hæmorrhage
which it has caused.

It has already been stated that it was uncommon during the war to
meet with patients who were suffering from anæmia uncomplicated by
traumatic shock. It was in fact the condition of shock which tended
to dominate the clinical picture, and it was towards the elucidation
of the facts concerning shock, its causation, prevention, and
treatment, that the investigations co-ordinated by the Medical
Research Committee were mainly directed. These investigations were
carried out both in the laboratory and in the military hospitals, and
considerable additions were made to the knowledge of the condition.
It is necessary to give some account of the conclusions which were
reached in order that the rôle of blood transfusion in the treatment
of shock may be fully understood.

Hæmorrhage and shock cannot be dissociated, and this is not only
because they so frequently occur together in the same patient, but
also because the manifestations of the two conditions are essentially
the same. In shock, as in hæmorrhage, are found the same pallor
of the face and mucous membranes, the same fall of blood pressure
and rapid pulse, the same perspiration, restlessness, and shallow
respiration. The symptoms following a severe hæmorrhage have
sometimes been referred to as constituting a “shock-like condition.”
As will be seen, however, it is more accurate to describe the
symptoms of shock as closely resembling those of hæmorrhage, and to
regard both conditions as a manifestation of deficient fluid content
in the circulation.

Numerous theories have been advanced to account for the symptoms
seen in shock. Until recent years it was customary to suppose
the vaso-motor centres had failed, being overcome by exhaustion
consequent upon excessive stimulation by a greatly increased number
of afferent impulses from the periphery of the body. It was suggested
that as a result there was a general dilatation of the vascular
system, especially in the abdominal veins, and therefore a general
impairment of the circulation. Various hypotheses were, in addition,
formulated, to account for the vaso-motor failure. These included
the ideas of deficient carbon dioxide in the blood, exhaustion
of the adrenal secretion, and exhaustion of nerve-cells in the
higher centres. All these theories found their supporters and much
experimental evidence was brought forward, but none was susceptible
of final proof. The whole theory of vaso-dilatation and the idea that
the patient “bleeds into his own abdominal veins” were eventually
disposed of by observation of the clinical facts. Many extensive
abdominal operations have been performed upon shocked patients, but
the accumulation of blood in the splanchnic area has never been
demonstrated. It has, on the other hand, been found that in the limbs
the arteries and arterioles are strongly contracted. It is also by
no means unusual to meet with the condition known as venospasm; the
veins are collapsed and their walls contracted, so that it becomes
necessary to use a considerable positive pressure before any fluid
can be induced to flow into them. It has, in addition, been shown
that the vaso-motor system is still active, and the heart, although
beating rapidly, still responds to reflex stimulation and to increase
of intracranial tension.

It becomes necessary, therefore, to find some other explanation of
the low blood pressure which is the essential feature of shock. Of
especial value in this connexion are the investigations by Keith,
already mentioned, into the changes in blood volume found in soldiers
suffering from shock and hæmorrhage. In very few of these cases
were the symptoms due to shock alone, but usually the loss of blood
volume was much greater than could be accounted for by the amount
of hæmorrhage which had taken place. Here, therefore, was evidence
strongly suggesting that the symptoms of shock are due to actual
loss of circulating fluid, and the problem now resolved itself into
a search for this fluid which has ceased to be part of the effective
blood volume. Enough has already been said to show that there is no
evidence that the larger vessels, whether arteries or veins, are
acting as reservoirs in which the blood is stagnating. It therefore
only remains to consider whether the capillary system is capable,
under abnormal conditions, of holding so large a proportion of the
blood as has been shown by Keith to have left the circulation. For
a discussion of this problem the reader may be referred to W. B.
Cannon’s summary of the arguments (45), from which it becomes clear
that the capillary system may be regarded as a potential reservoir
large enough to contain the lost blood in shock. The question is,
however, further complicated by the fact that the capillary blood in
shock differs from the circulating blood in containing an abnormal
concentration of corpuscles. Extensive observations made on wounded
soldiers have shown that the number of red blood cells may rise even
to 8,000,000 per cmm. in the capillary blood, while the number in
the venous blood remains at 5,500,000 or less. This concentration of
the red cells is gradual and progressive, and will by itself account
for a large part of the loss of volume, since normally the bulk of
the blood is made up of corpuscles and plasma in approximately equal
parts. The stagnation is, moreover, accentuated by the increased
viscosity of the blood resulting from the concentration, and by the
chilling of the surface of the body, which is always a feature of
the state of shock. A vicious circle is thus established, and the
symptoms of shock become severe as the capillary stagnation becomes
more pronounced.

A second factor which may also play its part in the loss of blood
volume in the general circulation is the exudation of some of
the plasma into the surrounding tissue spaces. As the stagnation
increases, oxygenation decreases, and the walls and the capillaries
become more permeable, so that some fluid is probably lost in this
way. This permeability may also be accentuated by the increased
hydrogen-ion concentration in the blood, which often accompanies
shock, but it seems to be clear that this is a secondary phenomenon
resulting from imperfect oxygenation in the tissues, and it will
therefore not be regarded as one of the factors responsible for
shock. Further fluid is lost by the copious perspiration commonly
seen in shock. There seems, therefore, to be a conspiracy between a
whole set of different factors all tending to deprive the patient
of his circulating fluid. The net result is a condition so closely
resembling hæmorrhage that it may be impossible to distinguish the
two, this difficulty being increased by the fact that they so often
occur together.

In the foregoing account of the production of shock the fate of
the lost blood has been discussed, but nothing has been said of
the factors initiating the capillary stagnation. This is a subject
which is of great interest and some obscurity, and is of evident
importance in considering how shock may be avoided. The present
treatise, however, is primarily concerned with the treatment of
shock when already established, and it is therefore not proposed to
follow out the other question in detail. An injury may be followed
immediately by a condition of “primary wound shock,” in which the
patient becomes suddenly pale and pulseless. This is a physiological
reaction, which may be transient, and it is to be distinguished
from the much more serious condition of “secondary wound shock”
which appears some time later. It is this secondary shock alone
which has been under consideration in the preceding pages. The chief
importance of the primary shock lies in the fact that it may initiate
the conditions which predispose to secondary shock, so that under
certain circumstances the one may become merged in the other. These
predisposing conditions are increased evaporation from the skin, a
general fall in the temperature of the body, mental anxiety, and the
continued stimulation of the higher centres by afferent impulses as
is manifested by pain. The condition of secondary wound shock was
shown in a striking degree, during the earlier years of the war,
by the men suffering from fracture of the femur. In the later part
of the war warmth was supplied more systematically than before to
the seriously wounded, and all fractured femurs were treated at an
early stage with Thomas’s splints. Two of the factors predisposing
to shock, namely cold and pain, were in this way to some extent
eliminated, and it was very striking how much better than before was
the general condition of the patients on arrival at the hospitals.

Nevertheless, the elimination of these factors, which is a simpler
matter in civil life than it was under conditions of war, will not
avert all shock in a large proportion of cases. It is necessary,
therefore, to find some additional factor which will initiate shock
in addition to the predisposing causes. It is thought that this
may have been identified in a substance of obscure nature which is
derived from the damaged tissues themselves, and which, circulating
in the blood, is able directly to affect the capillary system. Just
as the shock following severe burns is believed to be due to the
circulation of a toxic substance formed by the burning of the skin
and other tissues, so the shock following severe trauma is believed
to be of toxic origin, the toxin being derived from damaged tissues,
muscle being particularly active in this respect. The condition
may, therefore, be one of “traumatic toxæmia,” in which there is a
general loss of capillary tone throughout the body, so that “the
blood percolates into the network of channels as into a sponge.”
The circulating blood is thus rapidly depleted, and the symptoms
of shock become established. The investigation of this source of
shock was carried out chiefly by Dale, Bayliss and Cannon (65), who
were able to reproduce the condition of shock in animals by the
injection into their circulation of a substance obtained from damaged
muscles. To this substance the name histamine was given. It would be
a mistake, however, to suppose that because a substance producing
shock experimentally has been obtained from muscles, that therefore
this is the identical substance which is responsible for every case
of traumatic toxæmia. Extreme shock may be produced when but little
damage has been done to muscles. Probably damage to any tissue of
the body if extensive enough will produce a substance or substances
which will give rise to the symptoms, and it may be a long time
before these are isolated and identified. That the last word on the
production of shock is still far from being uttered is shown by the
fact that profound shock may be induced without doing any appreciable
damage to tissue, namely, by handling and exposing the abdominal
viscera.

It may be this traumatic toxæmia which will account for many cases of
post-operative shock, but it has been shown that some anæsthetics,
such as chloroform or ether, will of themselves greatly accentuate
shock initiated by other causes.

It has already been mentioned that the increased hydrogen-ion
concentration in the blood, which results from imperfect oxygenation
in the tissues, is not itself a cause of shock, but it will aggravate
shock due to other factors. A discussion of this will be found in the
paper by W. B. Cannon already referred to.

The present state of knowledge concerning the causation of shock
having been thus briefly reviewed, the question of the treatment
of the condition may be discussed. In this connexion the value of
blood transfusion will be considered. It will have become clear
that essentially the condition to be combated in treating shock is
one of lowered blood pressure following upon a diminution of the
volume of blood in the circulation. All the factors which have been
mentioned in considering the causation of shock must be combated.
Warmth must be supplied, morphia administered, fractures efficiently
immobilized, damaged tissues excised: but clearly all these measures
are prophylactic rather than curative. None of them will remove
a state of profound shock once established, for they will not of
themselves restore the blood volume depleted by capillary stasis.
It is necessary, therefore, to attack this condition directly. It
may with justice be compared to a state of acute anæmia following
hæmorrhage, but with this difference, that the blood is still present
in the body and will return to the circulation when the capillary
stasis has been abolished and the circulating balance has been
restored. The possibility of recovery from shock depends upon how
long the condition has existed. After a certain time the toxæmia,
whether the primary traumatic toxæmia or the secondary increase in
hydrogen-ion concentration, appears to have a damaging effect upon
the capillary walls, so that an increased loss of fluid takes place
into the tissues and this cannot be remedied. It is essential,
therefore, to use the means which will most rapidly restore the
circulation and bring about a rise in blood pressure which will be
permanent. It is reasonable to infer that the most hopeful means of
bringing this about is by a blood transfusion, which will actually
replace the blood temporarily lost. This is the physiological remedy,
and its value has been proved by the results obtained in many cases
of my own as well as in those recorded by others. The efficiency of
the treatment is accentuated by the fact that so large a proportion
of cases of shock are associated with, and aggravated by, some degree
of hæmorrhage. Apart from this, Keith’s observations have shown
that the diminution of blood volume in shock is comparable with
that which attends severe hæmorrhage. The state of shock in fact so
closely resembles hæmorrhage that most of the same remarks concerning
blood volume and the amounts that should be given by transfusion
may be applied, and it is unnecessary to repeat them here. It must
be remembered, however, that in pure shock the amount of hæmoglobin
in the body is not reduced though there is less in the circulation.
It is restored to the circulation when the capillary stagnation is
overcome. This will be referred to again later on.

During the war the value of blood transfusion in shock was amply
demonstrated. In civilian practice I have found it to be of value
when given after operations such as removal of the rectum, whether
by the perineal or abdomino-perineal route, amputation of the leg
through the hip joint, or removal of a sarcoma from the nasopharynx.
Transfusion should be given towards the close of the operation
before the evidences of shock have reached their maximum. The
depletion of the blood volume is then actually remedied as it takes
place, and transfusion becomes almost as much a prophylactic measure
as warmth and the administration of morphia.

It is probable that the mortality following very severe operations
such as those mentioned above would be considerably reduced if blood
transfusion were to be given as a routine measure. Reference has
already been made to the bad effect of the ordinary anæsthetics, and
the best effects are obtained by a blood transfusion in conjunction
with gas and oxygen or with spinal anæsthesia. It is necessary,
however, to draw attention to the fact that a blood transfusion if
given to a patient under the influence of a spinal anæsthetic must
not be performed until the operation is very nearly completed, for it
will very often produce a much more rapid return of sensation than
would otherwise occur.

In advocating the use of blood transfusion to combat the effects
of shock and hæmorrhage, it would be misleading to imply that this
is necessarily the only treatment that is available. Something
must be said of the substitutes for blood that have been used, and
in particular the value of gum acacia must be considered. In the
days before the war it was customary to treat post-operative shock
or hæmorrhage with large quantities of normal salt solution given
intravenously or subcutaneously. During the earlier part of the war
also this was used, and there can be no doubt that for the less
severe cases this treatment is often beneficial. Occasionally even
the lives of patients who were desperately ill have been saved by
it; I have seen a saline infusion cause the recovery of a man who
had a dozen perforations of the small intestine and who had, in
addition, lost several pints of blood intraperitoneally from a wound
of a large mesenteric vessel. Such cases are, however, exceptional.
In the presence of severe shock or hæmorrhage a saline infusion may
cause an immediate rise in blood pressure, but the fluid exudes so
rapidly into the tissues that the effect is usually very transient.
This fact is universally admitted to be true and need not be further
emphasized. Saline solution administered by the rectum is likely to
have a more lasting effect, but the process of absorption is slow,
and the patient may be dead before it has had time to act. The
same applies to water given by the mouth. A patient suffering from
severe shock is unable to tolerate more than a very small quantity
of fluid in his stomach without vomiting. Some success was attained
by Oswald Robertson in treating cases of hæmorrhage by the method of
“forced fluids,” large quantities being given by the mouth and by
the rectum (245). In many serious cases, however, this treatment is
inapplicable, and it is clear that transfusion is more rapid and more
certain in its effect. Isotonic saline having been found ineffectual,
it was suggested that a hypertonic solution (2 per cent. sodium
chloride) might be of more value. This was tested clinically and in
the laboratory, and was found to have no advantage over the isotonic
solution (11).

When the association of increased hydrogen-ion concentration with
shock was demonstrated, it was at first supposed to be one of the
factors producing the condition. It was therefore natural that the
effect of a solution of sodium bicarbonate (4 per cent.) should
be tried. The effect upon certain cases suffering from extreme
“acidosis” and air hunger was very striking, but in general the
alkaline solution was no more effective than the ordinary isotonic
saline. I soon abandoned its use for intravenous infusion, but it was
of service in serious cases when given by the rectum.

During the war the necessity for the conservation of time--and
of blood--was evident. The search for a satisfactory substitute
for blood was therefore prosecuted with great energy, most of the
research being done by, or under the direction of, Professor W. M.
Bayliss. The object of the research was to discover a non-toxic
solution which possessed the same “viscosity” as the blood, and the
same osmotic pressure due to contained colloid. It was believed that
such a solution would not tend to exude so rapidly into the tissues
and would therefore augment the blood volume more effectively than
the fluids previously used. After many experiments it was claimed
in 1916 that a blood substitute had been found in a 6 per cent.
solution of gum acacia with ·9 per cent. sodium chloride. It was
even stated on the evidence of laboratory experiments that the gum
solution was as effective as blood in the treatment of shock and
hæmorrhage. It was therefore used very extensively among the wounded,
and favourable reports upon its value were made by various workers.
It is difficult, however, to control the results in giving treatment
of this kind. If a patient dies after being given a gum infusion,
no one can state definitely that he would have lived had he been
given a blood transfusion instead. If a patient lived after having a
blood transfusion, it would be equally rash to state that he would
have died had he been given gum. Nevertheless, after giving the gum
solution a number of trials, I formed the opinion that the results
were inferior to those obtained with blood. Patients did not recover
whom from previous experience with blood transfusion I should have
expected to do so. I accordingly continued to use blood in preference
to gum whenever it was available, although justice must be done to
those who so strongly advocated gum by saying that there can be
no doubt that it is very much more effective than other solutions
previously used. The same opinion was formed by many other surgeons,
although it was natural to feel a bias in favour of gum which could
be given with much greater economy of time and effort than blood. Up
to the present time I have seen no reason for altering this opinion,
and should always prefer to treat hæmorrhage and shock with a blood
transfusion if possible.

Recently the relative values of a number of intravenous infusions
for shock have been put to an extensive experimental test by F. C.
Mann. The shock was produced by handling the abdominal contents,
and the effect on the blood pressure of the various fluids was
mechanically registered. The conclusion was reached that far the best
results were obtained by a transfusion of blood or blood serum, the
effect of these being more permanent than that of any other substance
used. The use of gum acacia was found to give results which were
“variable and sometimes disastrous,” but this may have been due to
some extent to errors in the technique of preparing the solution.

This draws attention to a possible objection to the use of gum,
namely, that some samples of the solution have been found to be
actually toxic; but it is said that this can be avoided if proper
care be exercised in its preparation. Full instructions for this are
given in a paper by S. V. Telfer.

Into the discussion of the relative merits of blood and gum solutions
may be profitably introduced the further question as to which is the
more valuable constituent of transfused blood, the corpuscles or the
plasma. It has been seen that the essential factor in producing the
symptoms of shock and hæmorrhage is a reduction of blood volume,
and treatment is therefore directed in the first place towards the
restoration of this volume, with a fluid of the same viscosity and
osmotic pressure as blood. This might be done with plasma or, some
may say, equally well with gum. From the point of view only of
volume, the corpuscles and plasma are of equal value, since each
forms approximately half the total volume of a given quantity of
blood. There is, however, another aspect to be considered. One of
the results of loss of blood volume is imperfect oxygenation in the
tissues. When the volume is increased by the addition of plasma or
gum, the corpuscles in the circulation are diluted, and this by
itself would tend further to impair oxygenation. The dilution is,
however, compensated for by the improvement in circulation which
in its turn improves the supply of oxygen to the tissues, and it is
still further counteracted by the restoration to the circulation of
the blood corpuscles which were stagnating in the capillary system.
It seems clear that these successive processes will be accelerated
by the use of a fluid which itself contains corpuscles, and this may
afford a theoretical explanation of the clinical observation that
blood is more effective than gum. Its use will tend to establish
more quickly the “virtuous circle” following increased volume, and
so undo the “vicious circle” due to insufficient volume. It has
been questioned whether the corpuscles of transfused blood really
do play an active part in the economy of their new host, or whether
their new environment may not quickly render them effete. This has
been answered by the exceedingly interesting and ingenious series of
experiments carried out by Winifred Ashby. She has transfused blood
of a known group (see Chapter IV) into an individual of a different,
but compatible group, and then shown that it is possible by selective
agglutination with a suitable serum to demonstrate the presence in
the blood of the two kinds of corpuscles side by side. In this way
she has shown that transfused corpuscles are still present in the
circulation and of normal appearance thirty days after they were
introduced.

It is therefore justifiable to make the inference that transfused
corpuscles can for some little time carry out their normal function.
If it be true that their presence is an advantage in the treatment
of deficient blood volume, it may also be conjectured that their
presence is likely to be of greater importance in treating hæmorrhage
than it is in the treatment of pure shock, for in the latter
condition all the original corpuscles are still present in the body,
while in the former they are not.

I should sum up the discussion of the relative merits of blood
and gum by saying that on the grounds of experiment and clinical
experience I believe blood to be the more efficient of the two,
particularly in the most serious cases. Every patient who needs it
should therefore have the advantages conferred by blood transfusion
if it can be done. If it cannot, then gum and saline is much the most
satisfactory substitute that is at present known.

Some of the concluding remarks in the foregoing pages will have
suggested that the use of gum infusion may be considered of more
value in treating pure shock than in treating hæmorrhage. For this
reason, apart from other diagnostic considerations, it may be of
importance to be able to distinguish clinically between shock and
hæmorrhage. Attention has already been drawn to the fact that the
symptoms and appearance seen in a patient suffering from severe shock
very closely resemble those seen in hæmorrhage. It may, in fact, be
impossible to say from purely clinical evidence whether a patient is
suffering from shock, or hæmorrhage, or both. A case which recently
came under my own observation well illustrates this point. A very
stout, elderly man had fallen down a lift-shaft and was brought into
St. Bartholomew’s Hospital soon after the accident. He appeared
to have fallen on his feet, and the lower ends of both tibiæ had
been driven through the inner sides of his soles, but there were no
other signs of injury. His general condition on arrival at hospital
was fairly good, but all the usual measures were taken to minimize
shock. An hour or two later he had passed into a condition of extreme
collapse, and exhibited all the symptoms which have already been
described. Not much hæmorrhage had taken place from the wounds in
his feet, and the question arose as to whether his present condition
was due to internal hæmorrhage from visceral injury, or whether it
was due chiefly to shock. His abdomen contained so much fat that no
evidence could be obtained from an examination of it, and it was in
fact impossible to arrive at any conclusion. There could, however,
be no question of performing any operation, and the patient made
no response to other treatment. At the autopsy it was found that
there were fractures of the ribs, spinal column, and symphysis
pubis in addition to the injuries to the legs. There was very little
hæmorrhage in connexion with any of the fractures, and it appeared
that death was to be attributed almost entirely to shock. This was
perhaps a somewhat unusual case, in which no help could be derived
from an examination of the patient, but similar difficulties will
sometimes be met.

It might be expected that a criterion would be supplied by an
examination of the blood. The results from this, however, have proved
to be disappointing. The facts have been investigated by Cannon and
others (47) and may be summarized as follows. The number of red
corpuscles in the blood from the capillaries of the ear or finger has
been found to be invariably raised in patients suffering from shock.
A blood count may show an increase up to seven million red cells per
cmm. or even more. The blood in the venous circulation, however, of
the same patient is more dilute, the count being less by one to two
million red cells. When the shock is complicated by hæmorrhage, the
blood count in the venous system will again be lower than that in
the capillaries, but in both the counts will be less than if there
were no hæmorrhage. The differences are, however, not so great or
so constant that any principle can be laid down by which the two
conditions may be distinguished. In patients in whom hæmorrhage is
the outstanding feature the blood counts will be still lower, but
the capillary and venous difference will still be present. It was
found that in hæmorrhage the hæmoglobin percentage, and therefore the
colour index, tended to be lower than in shock, but this was most
obvious when the hæmorrhage had been very severe, and in such cases
the diagnosis is usually clear from other evidences. The clinical
difficulty lies in the distinction between cases of pure shock and
of shock complicated by considerable hæmorrhage. It seems that
little help is to be derived from an examination of the blood. This
difficulty in diagnosis can only influence treatment in the direction
of giving blood rather than gum-saline, though the latter would
probably be effective for many of the cases of shock if they could be
distinguished.

The effects of transfusion for hæmorrhage and shock are to be
judged best by the clinical results. The abnormal distribution
of the corpuscles is altered by the treatment with a consequent
redistribution in the circulation. No constant changes, therefore, in
the blood count follow transfusion, and no exact mathematical effect
can be demonstrated. It has been shown by Huck that sometimes the
immediate rise in the blood count is greater than can be accounted
for by the amount of blood given. This is often followed by a fall,
which is succeeded in its turn by a second rise. These results are
to be explained by alterations in the amount of destruction and
formation of red cells going on in the body. That is to say, they are
biological rather than mechanical, and are at present but imperfectly
understood.

In the foregoing discussion hæmorrhage and shock have been considered
in a general way. Something must now be said of the particular
conditions for which transfusion may be given. Concerning traumatic
hæmorrhage and shock there is little to be added, for these
conditions present the general features of the problem in its least
complicated form. No clear-cut rule can be laid down as to the point
at which transfusion becomes necessary. The blood pressure is perhaps
the best single indication, and if this has fallen below 80 mm.
(systolic), then a transfusion is certainly indicated. Apart from
this, the patient’s general condition is the safest guide. As soon as
it becomes evident that his life is in danger, a transfusion should
be given. Better save a few lives by many transfusions than lose them
by reserving transfusion for those who are actually moribund.

Secondary hæmorrhage following an operation is fundamentally similar
to primary hæmorrhage, but may present a few additional points. In
recent years by far the largest number of transfusions for secondary
hæmorrhage have been given for bleeding from septic amputation
stumps. In many cases of this sort it is no easy matter to stop the
bleeding by ligaturing a bleeding vessel; sometimes it is impossible.
Nevertheless, transfusion should not be withheld owing to a risk of
increased hæmorrhage supposed to follow a rise in blood pressure.
Usually the patient is debilitated by prolonged suppuration, and
often his blood is deficient in its power of coagulation. It has
been found that a transfusion, in addition to replacing some of the
blood that has been lost, tends to improve the patient’s resistance
to micro-organisms, and to shorten the coagulation time of the blood.
Recurrence of the hæmorrhage is therefore discouraged on the whole,
and in many cases a series of transfusions for recurrent hæmorrhages
has saved a patient’s life when the prognosis had seemed to be almost
hopeless.

Post-operative hæmorrhage associated with chronic jaundice is another
condition which demands special consideration; this will be dealt
with later under the heading of hæmorrhagic diseases.

The proper treatment of severe hæmorrhage from a gastric or duodenal
ulcer has always puzzled physicians and surgeons alike. It is
probably true that patients very seldom die as the result of a
single rapid hæmorrhage, even if severe. There can, however, be no
doubt that death due actually to acute anæmia may follow repeated or
prolonged hæmorrhage. Hitherto treatment has been conducted mainly
on medical lines. Opinion is now, however, tending to favour earlier
and more frequent surgical interference, and this can be made a
less dangerous procedure by giving a preliminary blood transfusion
to improve the patient’s general condition. When the patient’s life
is threatened by hæmorrhage repeated or prolonged, transfusion is
undoubtedly the best means of saving him. Here again the fear of
restarting the hæmorrhage by raising the blood pressure has acted as
a deterrent, so that transfusion is apt to be withheld until too
late. Nevertheless, it is clear from the numerous cases recorded in
the literature that this fear is groundless (130, 215, etc.). The
effect of a transfusion on the coagulating power of the patient’s
blood more than compensates for the risk attending a rise in blood
pressure. Now only is lost blood replaced, but also the clot plugging
the damaged vessel is made more secure. The patient is tided over
the immediate danger to his life, and surgical treatment is made
possible. This view will doubtless meet with much adverse criticism,
but its justice will eventually be recognized.

As in the early days of transfusion, so at the present time, a
considerable proportion of the patients that need transfusion will
be met with in the course of obstetrical practice. It has often
been remarked how much blood can be lost by a woman following the
delivery of her child without any serious result; nevertheless,
many deaths are occasioned every year by post-partum hæmorrhage,
placenta prævia, and rupture of an ectopic gestation. Sometimes the
bleeding is so rapid that there is no margin of time available for
a transfusion unless all the facilities be immediately at hand.
Short of this, transfusion is the ideal treatment, and the problem
is a simple one, the relief of acute anæmia being the only object
in view. One interesting modification of the procedure has been
recently recommended by German writers, namely, the reinfusion of the
patient’s own blood. This is applicable only when the hæmorrhage has
taken place into the peritoneal cavity, and is therefore limited to
the treatment of a ruptured liver or spleen, a ruptured uterus, or
a tubal abortion. With a ruptured uterus the sterility of the blood
is not assured, and this condition were better not included. For the
other conditions Lichtenstein recommends that the blood should be
ladled out of the peritoneal cavity into Ringer’s solution and then
strained to remove clots. The resulting fluid is infused into a vein.
Judging from my own experience of intraperitoneal hæmorrhage, not
much blood would actually be recovered in this way, since usually
so much of it has clotted. In any case, the whole procedure is to be
looked upon with suspicion owing to the unknown and probably profound
changes that have taken place in partially clotted blood. Eberle
records that in one case reinfusion was followed by hæmolysis, and
among twenty-one cases reported by Schweitzer in 1921, one death
was attributed to the reinfusion, which, as in Eberle’s case, was
followed by hæmoglobinuria. Transfusion has also been used for the
toxæmias of pregnancy, but this will be dealt with under another
heading.



CHAPTER III

INDICATIONS FOR BLOOD TRANSFUSION--_continued_


HÆMORRHAGIC DISEASES

It is claimed that blood transfusion provides an efficient means of
treatment in most conditions distinguished by symptoms of spontaneous
hæmorrhage or by traumatic hæmorrhage which cannot be controlled. All
such diseases have the common features that the coagulation time of
the blood is abnormally prolonged, and it may be supposed that the
transfused blood supplies some missing constituent, so that for the
time the blood is enabled to coagulate more normally. Most of the
evidence available shows that the claims made for transfusion are not
exaggerated.


=Jaundice.=--It is well known how exceedingly dangerous an operation
upon a jaundiced patient may be owing to the difficulty of obtaining
hæmostasis. The coagulation time of the patient’s blood is not
affected in a transient catarrhal jaundice, but in the chronic
condition it has been shown to be three or four times the normal
(223). In these circumstances it is found that a transfusion is
of some use in shortening the coagulation time of the patient’s
blood so that bleeding ceases, although sometimes, especially in
cases of jaundice due to malignant disease in which the biliary
obstruction has not been relieved by the operation, the effect is
very transitory, and after two or three days the patient may again
begin to bleed (215). No other method of overcoming this has yet been
found to be more effective than transfusion, though the intravenous
administration of calcium compounds is sometimes of value.


=Hæmophilia.=--Blood transfusion is of still greater value when the
coagulation time of the blood is prolonged owing to a congenital
deficiency, as in hæmophilia. It is unnecessary to discuss here
in detail the precise nature of the deficiency. No definite
conclusion has yet been reached, though it seems to be clear that
the abnormality resides in the organic clotting complex, and not
in the calcium content of the blood. Treatment, therefore, will
aim at supplying the deficient substance, so that the coagulation
time may be reduced to normal, whereupon the bleeding will cease.
Various methods of bringing this about have been used. Horse serum or
whole blood injected subcutaneously has often been found effective
and sometimes even when used merely as a local application. Not
infrequently, however, horse serum fails of its effect, so that no
reliance can be placed upon it. Even when effective, the alteration
in coagulation time is transitory, a fact which introduces an obvious
objection to its use, for if the occasion should arise, as it easily
may, for a repetition of the treatment, the patient may be exposed to
the risk of severe anaphylactic shock.

Another form of treatment has been introduced by H. W. C. Vines, in
which a slight anaphylactic shock is deliberately induced, the result
of this being a fall in the coagulation time of the blood to normal.
The mechanism of this change is at present unexplained. Again, the
effect is transitory, but for a certain period afterwards a surgical
operation may be safely performed upon a hæmophilic patient treated
in this way. This method has not yet been extensively tested, and in
any case it cannot be used in an emergency, for the patient must be
sensitized by a preliminary injection and an interval of several days
allowed to elapse before the anaphylaxis can be produced.

The efficiency of blood transfusion in the treatment of hæmophilia
has been very often demonstrated, and seems at present to afford
the most certain means that we possess of arresting the symptoms.
Presumably the transfused blood supplies directly the deficient
factor in the coagulation complex, and it has been shown by Bernheim
(1917) that the transfusion even of quite a small amount of blood
will almost immediately stop the bleeding. In addition to comparative
certainty and rapidity in action, transfusion has the advantage
that it will replace the blood which has been lost, for often the
patient has reached a stage at which he is in danger of his life
from actual anæmia. This treatment, therefore, will always be useful
in an emergency, whether the patient be bleeding to death from a
slight wound, or whether he be suffering from acute appendicitis and
so is in need of an immediate operation. If transfusion does not at
once stop the bleeding, the treatment can be repeated, so that the
patient should not be allowed to die from loss of blood. In most
cases the bleeding will eventually stop if the patient’s life can
be prolonged. Even if the treatment be immediately successful, the
transfused blood necessarily contains only a limited quantity of the
substance necessary for the coagulation complex, and this gradually
disappears. Again, therefore, the effect is transitory, so that
transfusion is in no sense curative. It has been noticed that the
tendency of a hæmophilic to bleed decreases as age advances, and it
has been suggested by Ottenberg and Libmann that small quantities of
blood should be injected into his veins at regular intervals of one
to three months. It is possible that in this way he might be brought
safely through the more perilous years of his life.

The proof of the effect of transfusion upon the coagulation time
of the blood rests upon the evidence of a number of independent
observers. Pemberton has recorded a case of a hæmophilic whose
coagulation time before transfusion was estimated to be 23 minutes.
Blood was given to the amount of 500 cc., and 5 minutes later the
coagulation time was 3 minutes. Twelve hours later it was 8 minutes,
and on the fourth day after transfusion it had risen again to 20
minutes.

Other observations have been made as follows:

  -------------+-----------------------------+----------
               |      Coagulation time.      | Minutes.
  -------------+-----------------------------+----------
  Bulger       | Before transfusion          |   82
               |  1 day after transfusion    |   10
               |  8 days  ”        ”         |    8
               | 25   ”   ”        ”         |   40
  -------------+-----------------------------+----------
  Minot & Lee  | Before transfusion          |  150
               | After        ”              | normal
               | 3 days after transfusion    |   60
               | 5   ”    ”        ”         |  100
  -------------+-----------------------------+----------
  Addis        | Before transfusion          |  245
               | After        ”              |   24
               | 25 days after transfusion   |  200
               | After 8 cc. serum injected  |   38
  -------------+-----------------------------+----------

In treating jaundice or hæmophilia the transfusion may be performed
by the method of choice described in Chapter VII of the present work.
The addition of an anticoagulant to the blood does not render it any
less efficient as a hæmostatic agent. In all cases the coagulation
time of the patient’s blood is found to be reduced after transfusion,
whether sodium citrate be used as an anticoagulant or not. The
explanation of this may be found in the fact referred to on p. 120,
that the citrate is very rapidly destroyed in the circulation, and
so cannot for long influence adversely the hæmostatic properties of
normal blood.

The seeming paradox of using an anticoagulant in an endeavour to
promote the coagulation of the blood is heightened by the work of
Ottenberg, who has shown that the coagulation time may be reduced by
the intravenous injection of sodium citrate alone. In this experiment
20 cc. of a 3 per cent. solution of sodium citrate were injected into
a hæmophilic, whose coagulation time had been found to be 85 minutes.
Ten minutes after the injection it was found to be 25 minutes. Two
days later it had risen again to 85 minutes. This observation has
not been confirmed but, if it be true, citrated blood is likely to be
actually more efficient in the treatment of hæmophilia than untreated
blood.

The amount of blood to be transfused in hæmophilia will vary with
the age of the patient and according to whether he is suffering from
acute anæmia or not. If hæmostatic effects only are wanted, 100 cc.
of blood will be enough. If anæmia is also present, the dosage will
be governed by the same considerations as have already been discussed
in the section on the treatment of hæmorrhage.


=Melæna Neonatorum.=--Another hæmorrhagic condition in which blood
transfusion is of the very greatest value is that known as _melæna
neonatorum_. Severe hæmorrhage takes place from the bowel of an
infant, sometimes only a few hours after birth. The cause is quite
unknown, but it is found that absolute hæmostasis is usually brought
about by blood transfusion. Horse serum has often been successfully
used as in treating hæmophilia, but blood transfusion again has
the additional merit that the blood which has been lost is thereby
replaced. A single transfusion is usually enough, as the hæmorrhage
does not tend to recur when once it has been stopped. For a newly
born infant, even if _in extremis_, only a small quantity of blood
is needed, so that a transfusion of 50 to 100 cc. is usually found
to be enough. Bruce Robertson suggests that, as a good working rule,
the amount should not exceed 15 ccm. per pound of body weight. The
superficial veins of an infant are exceedingly small, so that the
introduction even of a fine needle into the median basilic may be
matter of the greatest difficulty. The best method of transfusing an
infant, therefore, demands special consideration. A description of
this will be found on p. 134 of the present work.

The value of transfusion for _melæna neonatorum_ has not been very
generally recognized, but a number of striking cases have been
reported. Defibrinated blood had been used in 1873 by Sir Thomas
Smith as described in Chapter I, but the first case in which whole
blood was used was published by Lambert in 1908. Later, in 1910,
Welch, and then Schloss, recommended the subcutaneous injection
of serum or of blood, but these measures were clearly not so
effective as the intravenous transfusion of blood, as has been
testified by numerous observers (Lespinasse, Unger, Vincent, Graham,
Bruce Robertson, Lapage, Hutchinson, etc.). The patients may be
actually moribund, for a new-born infant can only afford to lose
a relatively small amount of blood, but even then transfusion is
often successful. Bruce Robertson reports that of a series of forty
cases of hæmorrhagic disease of the new-born which were treated
by transfusion, all recovered except four; of these two died from
associated umbilical sepsis, one from intracranial hæmorrhage, and
the fourth had already ceased breathing when the treatment was begun.

It has sometimes been stated that for transfusing an infant either
parent can be safely used as blood donor, on the assumption that the
serum reactions are not yet developed. This may sometimes be true,
but the fallacies and possible dangers of this are explained in a
later chapter.

A case was recently reported by R. D. Laurie, who, knowing that he
himself belonged to Group IV, drew 20 ccm. of his own blood into a
syringe containing five grains of sodium citrate in solution. This he
injected into a vein in the infant’s arm; the small size of the vein
he had chosen made this difficult, but the treatment resulted in the
rapid recovery of the patient.


=Purpura.=--Of all the forms of hæmorrhagic diseases, the two already
described, hæmophilia and melæna neonatorum, are the only ones for
which blood transfusion is a really effective remedy. It is probable
that under the somewhat general term “purpura hæmorrhagica” are
grouped several conditions, all of very obscure origin, none of
which are conspicuously benefited by transfusion. Many transfusions
have been given for purpuric symptoms, chiefly in America. Several
cases are reported by Bernheim, and twelve transfusions were given
to seven patients by Peterson. In some of these the treatment
produced a temporary improvement, but usually they relapsed after
an interval of a few months. One of Bernheim’s patients appears to
have owed his life for the time being to a transfusion, but he died
subsequently during a recurrence. Two cases are reported by Graham.
One was not benefited at all; the other improved for a time, but
afterwards relapsed. In a serious case, therefore, transfusion may
be worth trying; it has indeed been stated by Ottenberg and Libmann,
observers with a wide experience of transfusion, that this treatment
is “definitely curative” in severe cases of purpura. At the present
time there is little to add on the subject, but it is possible that
further advances will be made by proceeding on these lines.


BLOOD DISEASES

=Pernicious Anæmia.=--Blood transfusion has been advocated for
several conditions characterized by alterations in the cells of
the patient’s blood. It has been used in the treatment of aplastic
anæmia, splenic anæmia, chlorosis, and leukæmia, but in none of these
diseases has it been of much avail. In pernicious anæmia, however,
transfusion has proved to be of very great service.

It is, indeed, now a recognized form of treatment for this disease,
though the numerous reports upon results that have been published
have not pronounced unanimously in its favour. Variability in
results probably depends to some extent upon the difficulty of
distinguishing true pernicious anæmia from some forms of secondary
anæmia. It is hardly to be expected that much benefit would follow
blood transfusion in the undiagnosed secondary type, since the
destruction or loss of corpuscles is continuous until the cause has
been removed. In true pernicious anæmia, on the other hand, there may
be remissions in the disease, and it is quite clear that these may
be initiated or prolonged by blood transfusion. The largest number
of consecutive cases that has been recorded was treated in the Mayo
Clinic in the years 1915 to 1918 (Archibald, Pemberton, Hunt). It was
estimated that in about 60 per cent. of the patients with pernicious
anæmia a definite improvement followed transfusion. It is generally
agreed that the best results are seen in those who have not yet
reached the last stages of the disease, though sometimes patients
who are actually _in extremis_ will also show great improvement. A
remarkable instance of this has been reported in Norway (261). A
man, aged thirty-three, was dyspnœic, semi-conscious, and moribund
when admitted to hospital. His red cells numbered 850,000 per cmm.,
and his hæmoglobin percentage was 19. Immediate improvement followed
the transfusion of 900 cc. of citrated blood, the red cells rising
quickly to 2,000,000 and later to 3,000,000. Twelve days after
admission he was walking about. No case must therefore be regarded as
hopeless, though disappointments must be expected.

As a general rule blood transfusion should be given before the
more serious secondary manifestations of the disease have shown
themselves, that is to say, some time before the condition has
become dangerous to life. Probably the disappointing results of this
treatment have partly been due to the fact that it has been regarded
as a last resort and has often been given at too late a stage. No
rule can be laid down as to when transfusion should be given, but
common sense suggests that it should be tried as soon as it is
evident that the disease is progressing in spite of other methods
of treatment. One authority (Anders) even advises that transfusions
should be given as soon as an assured diagnosis has been made, but he
weakens his case by adding that other methods of treatment should be
used at the same time. If the patient is already seriously ill when
first seen, the blood transfusion should be tried at once, as its
effect, if beneficial, is likely to be more rapid than that of any
other form of treatment.

The amounts of blood given in pernicious anæmia have varied. Massive
doses have occasionally been given (179), but the general opinion
seems to favour smaller amounts, 300-500 cc., the dose being repeated
at intervals of two or three weeks. Repeated transfusions have been
an outstanding feature of the treatment, and as many as thirty-five
transfusions of 500 cc. or more have been given to one patient,
extending over a period of thirty months. This is in itself a
demonstration of the fact that blood transfusion does not cure the
disease; the beneficial effect of each transfusion may wear off in
a short time, but by repeating the treatment the patient’s life can
be prolonged for months or even years beyond the time when it would
otherwise have ended.

Although the effect of transfusion is apt to be transient yet it is
certain that its good effects are due not merely to the addition
of a certain number of healthy corpuscles to the circulation, but,
in addition, to an obscurer factor. This can best be expressed by
saying that the transfused blood appears to have a stimulating
effect upon the blood-forming tissues of the patient, so that more
red corpuscles are discharged into the circulation. One observer
believes that enumeration of the reticulated red cells may be used
as an indication of the hæmopoietic powers of the bone marrow (289).
The reticulated appearance is assumed to be characteristic of cells
which have recently entered the circulation. The mode in which this
stimulus acts is unknown, and the whole subject calls for further
investigation. That this does take place is well illustrated by the
following details of three cases from Dr. Drysdale’s wards at St.
Bartholomew’s Hospital. The transfusions were given by Dr. Joekes,
who was also responsible for the estimations of the corpuscles.

[Illustration: Fig. 3.--PERNICIOUS ANÆMIA, CASE I]

I. A woman, aged 51, had been treated for four years for pernicious
anæmia, and when admitted to hospital was becoming steadily worse.
The red corpuscles numbered 1,470,000 per cmm., and her hæmoglobin
percentage was 32 on October 21, 1918, and by November 19 they had
fallen to 750,000 and 25. On November 22 she was transfused with 500
cc. of citrated blood, and a blood count made immediately afterwards
showed that she then had 1,410,000 red cells per cmm. On December
12 the number had risen to over 3,000,000, and on January 28 of the
following year it was over 4,000,000. This was still maintained
in May, 1919, and on the last occasion on which a blood count was
made she was found to have 4,400,000, with a hæmoglobin percentage
of 90. Since then she has been lost sight of, but would certainly
have returned had she relapsed. This case shows what remarkable
results sometimes follow a single transfusion and the progressive
improvement which follows the initial rise. The diagram shows the
results more graphically.

[Illustration: Fig. 4.--PERNICIOUS ANÆMIA, CASE II]

II. A similar result, even more striking, was obtained in a woman
aged 42. She was treated medicinally for four months, during which
time her red cells steadily decreased from 1,250,000 to 429,000 per
cmm. She was then transfused with 400 cc. of blood, and her blood
count rose immediately to 967,000. The rise continued steadily, and
three months later her blood count was 3,690,000 per cmm. Two very
small additional transfusions were given during this period, but to
what extent these helped in the treatment cannot be estimated. The
results in this case also are represented graphically by the diagram
above.

[Illustration: Fig. 5.--PERNICIOUS ANÆMIA, CASE III]

III. A less favourable result is illustrated by the following
history: A stores assistant, aged 47, had been ill for two years,
and was first treated for pernicious anæmia in April, 1920. He was
medicinally treated with arsenic, but no improvement followed. On
June 18, 1920, his corpuscles numbered 1,060,000 per cmm. He was
transfused with 600 cc. of blood, and his corpuscles increased at
once to 1,840,000 per cmm. A month later there had been a further
increase to 2,520,000, but this was not maintained, and nine months
afterwards he was given a second transfusion of 500 cc. of blood.
Immediately after this his red cells numbered 1,800,000 per cmm.
(April 14, 1921). There was a further slight rise and then another
rapid fall, so that on June 4, 1921, he had only 830,000 red cells
per cmm. He was then given a third transfusion of 700 cc. The effect
of this was a steady rise, and on June 17 he had 2,112,000 red cells
per cmm. A fourth transfusion of 500 cc. was given at this point, and
thereafter the improvement was maintained, with slight variations,
until, on August 4, 1921, his corpuscles numbered 3,450,000 per cmm.

In this case the effect of the two first transfusions was
short-lived, but perseverance with the treatment brought him in the
course of two months from an extremely serious condition to a state
of comparatively good health, in which he could again for a time
go about his business. The diagram illustrates well the rise which
followed each of the later transfusions. He had again relapsed four
months later, but, unless each transfusion had chanced to coincide
with the remissions which may occur spontaneously in this disease, it
seems clear that the treatment greatly relieved him for a time.

There is no objection to the use of citrated blood for pernicious
anæmia, so that the transfusion can be carried out in the ordinary
way described in Chapter VII. It is necessary, however, to utter a
warning as to the choice of a blood donor. It is quite clear that
in some patients, whose disease has been diagnosed as pernicious
anæmia, there is an alteration in the reactions of the serum. The
corpuscles may show an agglutination which conforms to one of the
group tests described in Chapter VI; nevertheless, it is essential in
addition that the patient’s serum should be tested directly against
the corpuscles of the proposed donor, even if he belongs to Group
IV, whose corpuscles are not agglutinated by the serum of any normal
person. I was recently asked to transfuse a patient whose disease
had been diagnosed as pernicious anæmia. Her red blood cells had
fallen to 600,000 per cmm., so that she was probably in the last
stages. Her corpuscles were agglutinated only by serum of Group
III, so that she apparently belonged to Group II. Only two donors
were available, both of whom belonged to Group IV. Nevertheless,
the patient’s serum strongly agglutinated the corpuscles of both of
them, so that I considered it inadvisable to carry out the treatment.
Similar abnormalities have been noticed by others. It seems to be
a universal experience that slight reactions are more commonly met
with after transfusion for pernicious anæmia than when it is done
for other conditions, although these do not in any way prejudice
the results that are obtained. These reactions are possibly to be
explained by abnormalities, though of slight degree, in the patient’s
serum. In a case such as I have described the reaction would
probably be very severe, if not fatal. It is possible also that a
well-marked alteration in the serum reaction is not characteristic
of the clinical entity constituting true pernicious anæmia, but in
reality indicates that there is another underlying cause for the
anæmia, such as an undiagnosed carcinoma. Dr. Joekes has recently
(August 1921) told me that he believes from his own observations that
this is actually the case, but it needs to be established by further
investigation. The connexion between malignant disease and abnormal
serum reactions is referred to elsewhere (p. 93).

Another possible complication is introduced into the treatment by
the necessity for giving repeated transfusions. It has been noticed
that sometimes a serious reaction follows one or more of the later
transfusions of a series, even when the blood is taken from the
same donor who had been used before without ill effects. A report
on several such cases shows that this form of reaction cannot be
predicted or eliminated by the most careful testing beforehand for
reactions between the patient’s serum and the donor’s corpuscles,
though it has occasionally been so severe as actually to hasten the
patient’s death (34). This fact suggests that the reaction is not
due to the presence of agglutinins, but is rather of the nature of
an anaphylactic shock, the patient having been sensitized by a trace
of foreign protein introduced in the blood on the earlier occasions.
Possibly it may be to some extent avoided by not using the same donor
if another is available. It also emphasizes the necessity for giving
the blood slowly and cautiously, so that the transfusion may be
stopped at the first sign of a reaction in the patient.

Very large numbers of transfusions for pernicious anæmia have been
given in the past, yet a reaction of a dangerous severity has
occurred in but few of them. This need not, therefore, be regarded as
a contra-indication for transfusion, but rather as an indication for
circumspection in giving it. Transfusion is clearly a therapeutic
measure of great value.

Very recently it has been claimed by Waag that excellent results have
been obtained by the repeated _subcutaneous_ injection of small doses
(5 cc.) of whole blood. In an actual case which he reports, nine
injections were given twice weekly. If the claim be substantiated by
further successes, this method of treatment may eventually supplant
the more elaborate process of actual transfusion.


TOXÆMIAS

_Bacterial Infections_

=Pyogenic.=--The value of vaccines and bactericidal sera in pyogenic
infections, though not in universal favour, is strongly advocated
by many competent authorities, and the transfusion of blood from an
immunized donor suggests itself as a natural corollary. A quantity of
blood taken from a vigorously reacting man and given to a debilitated
patient should theoretically supply him with a large amount of
the antibodies of which he stands in need. During the war it was
found that transfusion enabled an exsanguinated patient better to
withstand the attacks of pyogenic and putrefactive organisms in
his wounds, but this was probably due to the improvement in the
general circulation which resulted rather than to any bactericidal
properties in the transfused blood. It is known that outside the body
blood has considerable powers of inhibiting the growth of bacteria,
but ordinarily it does not possess bactericidal properties. It has
been claimed, on the other hand, that the best criterion of the
degree of immunity in an immunized animal is the measurement of the
bactericidal power of its blood. There is justification therefore
for attempting to combat a pyogenic infection by the transfusion of
immunized blood.

This method has at present not progressed beyond the stage of
preliminary trials. I have attempted it in one case, but without any
obvious benefit. The patient was a middle-aged man suffering from a
chronic staphylococcal septicæmia and a secondary anæmia. He received
a transfusion of 650 cc. of blood from a donor who had himself just
recovered from a severe infection with staphylococcus aureus. The
patient’s red blood cells underwent a temporary increase in number,
but no other result was observed. One series of nine cases has been
recorded by Fry, and in these the results leave some doubt as to
the efficacy of the treatment. Six of these patients were almost
hopelessly ill with streptococcal (five) or staphylococcal (one)
septicæmia, and only one of these responded to treatment. He received
transfusion from an ordinary donor and two from immunized donors,
who had been given five or six injections of a mixed vaccine, the
maximum dose of which contained 120,000,000 streptococci. Improvement
definitely followed the transfusions, and his recovery was afterwards
encouraged by injections of an autogenous vaccine. The other five
patients received similar treatment, but all died. The remaining
three patients had chronic suppuration, one following a streptococcal
arthritis of the knee, but no septicæmia, and all recovered. It
cannot be assumed that these recoveries were due to the transfusions.

It is stated by Waugh that he transfused nineteen cases of pyæmia of
whom twelve recovered, and in these cases an ordinary donor was used.
No details, however, are given, so that it is not possible to make
any inferences from this.

Greater success is claimed by Hooker, who reported that in five
cases of pyogenic infection the results were distinctly favourable.
He used immunized blood, but has formed the impression that the
transfusion even of normal blood is of value in septicæmia by
correcting the anæmia and helping to restore the normal resistance.
He recommends that if the patient has a good blood volume and a high
bacterial content in the blood, he should be bled by venesection
before transfusion. A striking case of staphylococcal septicæmia has
been recorded by Little, who believed that the patient’s recovery
was directly due to the treatment. Four transfusions were given,
the blood for three of these being taken from donors who had each
received, four days previously, an injection of vaccine made from
the patient’s own infection. Ottenberg and Libmann have treated ten
cases of pyogenic infections with transfusions. All the patients were
extremely ill and six died. It is stated that the four who recovered
“probably owe their lives to the transfusion,” but obviously it
is difficult to control the results. The same observers have
used transfusion in the treatment of infective endocarditis, but
unsuccessfully.

Some experimental work on this subject has been carried out by Kahn.
A bacterial infection was introduced into the peritoneal cavities
of several dogs. Continuous transfusion between an infected dog
and a healthy dog was then performed, the blood passing to and fro
between the animals, sometimes for over an hour. It was found that
all the transfused animals fared better than those that were not. The
experiment suggests that resistance to infection is heightened if
two bodies can combat the infection present in one; but continuous
transfusion is scarcely practicable in man.


=Diphtheria.=--In the later stages of some acute diseases due to a
bacterial infection, the patient falls into a condition of acute
toxæmia, the symptoms of which resemble in some ways those of shock.
Harding has drawn attention to this condition in diphtheria; he has
produced it experimentally in animals and has treated it by blood
transfusion. The toxæmic stage was found to occur on the fourth
to the eleventh day. It was characterized by a reduction of the
output of the heart with a corresponding fall in blood pressure,
an exudation of lymph into the tissues, and an increased specific
gravity of the blood. In all these respects it resembled the collapse
due to trauma or to hæmorrhage, and it was shown by experiment that
the treatment must be directed towards increasing the amount of
effective fluid in the circulation and to decreasing its viscosity.
It was found that normal saline solution failed to do this;
gum-saline solution also failed, and tended to produce a pronounced
agglutination of the red blood cells. Blood transfusion, on the
other hand, resulted in a considerable number of recoveries. In the
aggregate more than twice as many animals survived after transfusion
as survived without it, the same amount of toxin being given in each
case.

These experimental findings are exceedingly suggestive, but the
clinical efficacy of the treatment still remains to be proved.
Harding found that the amount of blood that should be transfused
was one-fifth of the total blood volume; the following amounts are,
therefore, recommended for the treatment of children in the toxæmia
stage of diphtheria:

  --------------+-----------+-----------
    Age.        |  Weight.  |  Amount.
  --------------+-----------+-----------
  1½ years.     |  21 lbs.  |  160 ccm.
  2    ”        |  28  ”    |  200  ”
  4    ”        |  35  ”    |  300  ”
  6    ”        |  42  ”    |  400  ”
  --------------+-----------+-----------


=Pneumonia.=--A condition of toxæmia similar to that seen in
diphtheria was also observed in some of the cases of pneumonia which
complicated the influenza epidemic of 1918-19. In the United States,
among a large number of cases admitted to an emergency hospital, a
series of 28 patients, some of whom were moribund, was treated by
blood transfusion by Rose and Hund. The results were compared with
those in 21 similar cases which were not transfused. The figures
seemed to show that transfusion was of some value. Of the 28 who
were transfused, 6, or 22·4 per cent., died, and the rest recovered;
of the 21 who were not transfused, 9, or 47·7 per cent., died, and
12 recovered. The numbers treated are not large enough to afford
statistical evidence that can be relied upon, but the results were at
least encouraging.


=Typhoid, Measles, Tuberculosis.=--Transfusion has been tried for
several other bacterial infections with varying results. McClure has
administered immunized blood to a typhoid patient with a remarkably
good result. Ottenberg and Libmann have transfused five typhoid
patients, all of whom were desperately ill; two of them recovered.
Transfusion has also been used for intestinal hæmorrhage in typhoid,
but this is chiefly with the object of combating anæmia. Subcutaneous
injection of blood has been successfully used by Terrien in a case of
malignant measles; the donor had had measles six months previously.
Freilich has recently transfused six patients suffering from
tuberculosis, but without benefit. He is at present testing the use
of blood from donors who show a positive complement fixation test for
the tubercle bacillus.

It is evident that treatment with immunized blood is still in
an experimental stage, but it merits further trials, all the
circumstances of which should be carefully recorded.


=Toxæmias of Pregnancy.=--The treatment of eclampsia by blood
transfusion was first employed by Kimpton, who speaks favourably of
the results obtained. Later it was independently suggested to Blair
Bell, who was the first to employ it in this country, by certain
investigations into the facts of immunology. It had been found that
symptoms resembling those of eclampsia could be produced in mice by
injecting into them an extract of placenta, whether from a healthy or
an eclamptic woman; the same results were obtained by injecting fresh
serum from similar individuals. Further, if the placental extract was
mixed with serum from a normal person of either sex, the effects were
not obtained, and it was inferred that the placental toxin had been
neutralized by antibodies in the serum. If, however, the placental
extract was mixed with serum obtained from the blood of an eclamptic
patient, then the toxic symptoms were obtained as before. Apparently,
therefore, the serum in eclampsia lacks certain antibodies which are
present in the serum of normal individuals. If these observations
had been correctly interpreted, it seemed reasonable to suppose
that blood from a normal person would supply an eclamptic patient
with the antibodies which she lacks. The patient treated by Blair
Bell was already comatose and apparently dying. She was given 500
cc. of citrated blood and rapidly recovered; her convalescence was
uninterrupted. It would be unwise to found great hopes on a single
case, but the treatment undoubtedly merits further trial.

Transfusion has also been used by Keator in treating the toxæmia
of early pregnancy, and Morel has successfully used the blood of a
healthy pregnant woman for the same purpose. Gettler recommends the
use of alkalinized blood for “acidosis” in pregnancy. At present,
however, little evidence can be adduced in favour of this form of
treatment.


=Nephritis.=--A single case of nephritis successfully treated by
blood transfusion has been recorded by Ramsay. The patient, a man
aged 22, had been ill for ten days. He was slightly drowsy and had a
furred tongue. His systolic blood pressure was 100 mm. and diastolic
60. His urine had a specific gravity of 1010, and contained much
albumin and many granular casts, but no blood cells. Vomiting was
incessant. On the second day after admission he passed 2 ozs. of
urine and his systolic blood pressure fell to 90 mm., his diastolic
to 40 mm. His low blood pressure and the evident imminence of
suppression of urine suggested the administration of blood; he was
accordingly given 1,140 cc. of fresh blood. His blood pressure
immediately rose to 100 mm. systolic, and 50 mm. diastolic, and
the other symptoms abated. He passed 24 ozs. of urine during the
ensuing twenty-four hours. He was afterwards treated with alkalies,
intravenously and by the mouth, and his condition steadily improved.
It cannot be inferred from the evidence that his recovery is to be
attributed entirely to the transfusion, but it appears to have been
initiated by this treatment, which was a reasonable one in view of
the symptoms. No other similar cases have as yet been recorded.


=Carbon Monoxide Poisoning.=--In any condition in which the function
of a large proportion of the red blood cells as oxygen carriers
has been temporarily destroyed or impaired, it is a rational
procedure to replace as many of them as possible with normal red
cells. The evidence that transfused blood cells can carry out their
functions in their new host has been given on another page. In
carbon monoxide poisoning the oxyhæmoglobin has been converted into
carboxyhæmoglobin, which is more stable than the oxygen compound, and
therefore useless for purposes of respiratory exchange. Undoubtedly
the ideal treatment for carbon monoxide poisoning is by putting the
patient in a specially constructed chamber in which he can breathe
oxygen under a pressure of about three atmospheres. By this means
the carboxyhæmoglobin is dissociated and replaced by oxyhæmoglobin.
An oxygen chamber is usually not available, though a very useful
substitute may be tried in the shape of a Haldane’s oxygen mask.
Failing this, there is evidence to show that a blood transfusion is
an effective form of treatment. Nevertheless, although poisoning with
coal gas is by no means a rare event, this treatment does not seem
to have had the attention it undoubtedly deserves. Transfusion was
first used for carbon monoxide poisoning by Hüter in 1870, who was
able to record a case in which recovery appeared to have been due to
the treatment. It was also advocated by Lauder Brunton in 1873. After
this date recorded cases are few, but in 1916 Burmeister put this
form of treatment on a more scientific basis by direct experiment.
Using rabbits and dogs he showed that if the animals treated with
coal gas were transfused without a venesection, 75 per cent. of them
recovered. Of a series of control animals, which were not transfused,
nearly all died.

Most writers on the subject have recommended that as much blood
be taken from the patient by venesection as is to be replaced by
transfusion. On theoretical grounds this seems to be sound, though
it is not supported by the results of Burmeister’s experiments.
Nevertheless, in a recent series of seven cases reported by Bruce
Robertson, in which 1,000 cc. of blood were removed and the same
amount given by transfusion, satisfactory results were obtained. If
no venesection is done, there is some risk that the transfusion may
put an additional load upon an already over-strained right heart,
so that a preliminary venesection is certainly a wise precaution.
Transfusion should not be withheld until the patient is _in
extremis_; if no oxygen chamber is available, it should be given
at once. A minimum amount of 750 cc. of blood should be taken by
venesection, and 1,000 cc. of blood should be given. If the patient’s
condition does not then show enough improvement, this should be
repeated.


=Nitrobenzol and Benzol Poisoning.=--Blood transfusion for poisoning
with nitro-benzol (C_{6}H_{5}NO_{2}) has been recommended by
Hindse-Nielsen, who records a case in which it was successfully
employed. The patient, a girl of 19, had taken a tablespoonful of
the poison several hours before, and her condition appeared to be
hopeless. She was deeply cyanosed, the mucous membranes being of a
dark blue colour. Washing out the stomach and inhalation of oxygen
were tried without effect. Finally she was bled to the extent of
600 cc., and 1,000 cc. of citrated blood were injected. Her colour
at once became more normal and recovery followed. The literature
does not contain records of any other cases treated in this way,
but the condition is analogous to coal-gas poisoning referred to in
the last paragraph, oxyhæmoglobin being in this case replaced by
methhæmoglobin, and its treatment by transfusion has, therefore, a
rational basis.

A somewhat similar condition is seen in benzol poisoning, though
there is an additional destruction of red blood cells. Three cases
treated by transfusion have been reported by McClure. One patient,
whose red blood cells had been reduced to 1,460,000 per cmm., was
extremely ill, but recovered after five transfusions up to a total
amount of 1,500 cc.


=Diabetes.=--Blood transfusion has been used in treating diabetes
mellitus, but there is no evidence to show that it is of any service.
Ottenberg and Libmann transfused four patients who were already in
diabetic coma, but no improvement resulted. Another patient who was
transfused by Raulston was actually made worse, as was indicated by
an increased output of sugar, acetone, and ammonia compounds.


=Pellagra.=--The precise ætiology of pellagra being still unknown,
treatment of the disease can only be empirical. From this point of
view blood transfusion has been tried by Cole, who began using it
in 1908. The results in twenty cases have been reported, and are
distinctly encouraging. All the transfused patients were in the
last stages of the disease, but nevertheless a recovery rate of 60
per cent. was obtained, the usual rate being 10 to 20 per cent. In
the present state of knowledge comment is scarcely possible, but
if pellagra is, as some observers have suggested, a “deficiency
disease,” it may be supposed that the transfused blood provides a
temporary supply of the substance that is lacking; the patient is
thus enabled to start along the road to recovery.



CHAPTER IV

DANGERS OF BLOOD TRANSFUSION


Appreciation of the dangers attending the practice of blood
transfusion has varied greatly at different times. In the seventeenth
century a happy ignorance took no account of them whatever. In the
eighteenth century they were so greatly feared that transfusion fell
into abeyance. In the nineteenth century it was realized that dangers
existed, but they were imperfectly understood; when fatalities
occurred, a partial knowledge explained them away more easily than
our fuller knowledge can to-day, so that transfusion was practised in
spite of them. At the beginning of the twentieth century, with the
discovery of “blood groups,” it was thought that all danger had been
eliminated. At the present time the pendulum is swinging back again,
and the problem of the complete elimination of danger is proving more
complex than it was thought to be a few years ago.

The chief dangers of blood transfusion are two-fold--that of
introducing into the recipient a disease carried by the donor, and
that due to the inherent properties of the donor’s blood which may
interact in a serious manner with the blood of the recipient. The
first of these dangers is obvious, and common sense will suggest what
steps should be taken to avoid it. Danger of communicating disease
is almost restricted to conditions in which an infective agent is
actually circulating in some form in the blood. Inquiry will usually
be enough to establish the possible presence in the prospective
donor’s blood of an organism such as the malaria parasite.
Nevertheless, a case has been recorded by van Dijk, in which malaria
was transmitted by injecting into a patient suffering from influenza
some serum obtained from another patient who was supposed to be
convalescent from influenza, but had been treated for malaria a few
months earlier. Another case is reported by Bernheim, who transmitted
a double infection of malaria--tertian and æstivo-autumnal--by means
of a blood transfusion. Blood infections, such as those due to the
exanthemata, may be avoided by the precaution of never employing a
blood donor who shows any signs of present illness, even though a
raised temperature be the only symptom. In certain cases, when, for
instance, the prospective donor may be suffering from tuberculosis in
some form or from gonorrhœa, the organism is extremely unlikely to be
present in the blood in numbers sufficient to communicate disease.
Nevertheless, on general principles, such donors should be eliminated
if circumstances permit. The most subtle form of infection, the most
dangerous, and the most difficult to eliminate, is syphilis. Definite
cases have been recorded in which syphilis has been communicated by
blood transfusion. In one instance recorded by Sydenstricker and
by Bernheim a father was infected by blood taken from his son, who
had refused beforehand to allow himself to be tested. Fortunately
such occurrences are rare. Still rarer and still more curious is the
transmission of horse asthma recorded by Ramirez. In this instance,
in which the disease is to be regarded as a form of anaphylaxis, the
patient had received an amount of serum sensitive to horse protein
great enough to provide him with the corresponding symptoms for some
time afterwards.

If the transfusion is being done at leisure, the donor’s blood
must be tested for a positive Wassermann reaction. Even this test,
however, has been known to fail, and since, in an emergency, the
most careful inquiry, aided by a desire on the part of the donor to
arrive at the truth, may reach an erroneous conclusion, the risk of
infection with syphilis can never be completely eliminated. Since
reasonable care can make the danger a remote one, it need not hinder
the performance of a transfusion any more than an occasional death
under anæsthesia prevents the frequent use of general anæsthetics.
The mere existence of such a danger is, however, an argument in
favour of the general use of the “professional blood donor,” whose
Wassermann reaction, personal history, and mode of life are well
known to the practitioner; the previous use of his blood on perhaps
more than one occasion, if unattended by any ill results, will give
an added confidence. The tragedy of such a misfortune is so great
that no precaution which can possibly be taken should be regarded as
absurd.

The second danger present in the inherent qualities of the donor’s
blood has been already alluded to in the historical sketch of the
subject. Before the existence of the “blood groups” was realized, a
number of fatalities due to an unexplained cause had occurred. Even
after the existence of the groups had been demonstrated, the warning
that resulted was apt to be disregarded, and it was not until still
further fatalities due to this incompatibility of bloods had taken
place that the very important nature of the discovery came to be
understood. The chances are, on the whole, that the blood of any
donor chosen at random will not prove fatal to a given recipient;
nevertheless, it must frequently happen that the transfusion
without being fatal will be wasted, or to some degree detrimental.
It is therefore evident that the existence of blood groups must be
seriously regarded, and it is necessary to enter into a detailed
consideration of their relations to one another and the symptoms
which they may produce. In the next chapters will be found a further
description of their physiology and pathology and of the methods of
testing for them.

It has long been known that if the blood of one species of animal
is injected into the circulation of another species, the corpuscles
of the foreign blood are at once destroyed, their contained
hæmoglobin being set free. This process of hæmolysis is under such
circumstances rapid and complete, and hæmoglobin may appear in the
urine in a short time. The precise nature of the reaction is obscure
and need not be discussed here in detail. The present bearing of
the phenomenon is the fact that a similar, or analogous, reaction
may occur when the bloods of certain individuals are mixed with
the bloods of certain others even of the same species. It was the
observation of this fact that first led to the discovery of the
so-called “blood groups” among human beings, and so to the partial
elucidation of the cause of the previously unexplained fatalities
following blood transfusion. In 1901 Landsteiner had detected the
presence of hæmolysins and iso-hæmolysins in blood and classified
three groups in human beings. In 1907 it was shown by Jansky that
human beings may be divided into four groups, the blood of the
members of each group having a certain definite relation to the blood
of the other groups as determined by the manner of their interaction.
The work was repeated and confirmed by Moss in 1910. The reaction
takes place between the serum of one group and the corpuscles of the
other groups, and is evidenced by the agglutination or hæmolysis
of the corpuscles that are being acted upon. In the course of his
researches Moss showed that hæmolysis, or the breaking up of the
corpuscles, is always preceded by agglutination or the clumping
together of the corpuscles. The process does not necessarily go as
far as the destruction of the corpuscles, but may be arrested at the
stage of agglutination. It may, on the other hand, be as rapid and
complete as if the bloods belonged to different species, and the
appearance of hæmoglobin in the urine may quickly give evidence of
this.

The groups have been arbitrarily numbered, and it is now usual to
refer to them by the Roman numerals I, II, III, and IV. According to
the accepted convention, the reactions of these four groups are as
follows:[5]

The corpuscles of Group I are agglutinated by the sera of II, III,
IV. The corpuscles of Group II are agglutinated by the sera of III,
IV. The corpuscles of Group III are agglutinated by the sera of II,
IV. The corpuscles of Group IV are not agglutinated by any of the
other groups.

On the other hand:

The serum of Group I agglutinates no other corpuscles. The serum of
Group II agglutinates the corpuscles of Groups I, III. The serum of
Group III agglutinates the corpuscles of Groups I, II. The serum of
Group IV agglutinates the corpuscles of Groups I, II, III.

This may be represented more graphically by the following table, a +
indicating agglutination, a - indicating no reaction:

  -------------------+-----------------------+
                     |         Serum         |
                     +-----------------------+
                     |  I  |  II | III |  IV |
  ------------+------+-----+-----+-----+-----+
  Corpuscles  | I    |  -  |  +  |  +  |  +  |
              +------+-----+-----+-----+-----+
              | II   |  -  |  -  |  +  |  +  |
              +------+-----+-----+-----+-----+
              | III  |  -  |  +  |  -  |  +  |
              +------+-----+-----+-----+-----+
              | IV   |  -  |  -  |  -  |  -  |
  ------------+------+-----+-----+-----+-----+

The active principle in the serum is called “agglutinin” or
“hæmolysin,” according to the degree of the reaction, and the
corpuscles are rendered sensitive to this by the possession of
an “iso-agglutinin” or “iso-hæmolysin.” Sometimes the corpuscles
are said to have “agglutinophilic” properties. It may be stated,
therefore, that the serum of Group I entirely lacks agglutinins,
whereas the corpuscles of Group IV lack iso-agglutinins. All these
terms, like the “amboceptors,” “receptors,” and “haptophores” of
Ehrlich, are used to conceal ignorance rather than as an expression
of knowledge, but, until more light has been shed upon the nature of
the reactions, ignorance must be abbreviated.

It is now clear that the blood as a whole contains two sets of
reactions which are independent. These properties reside in the
serum and in the corpuscles respectively, and the reactions are
complementary between Groups II and III, that is to say, the serum of
each group agglutinates the corpuscles of the other. It will be seen
from the table that the serum of Group I blood does not agglutinate
the corpuscles of any of the other groups, and conversely the
corpuscles of Group IV are not agglutinated by the serum of any of
the other groups. Individuals of Groups I and IV have therefore been
named “universal recipients” and “universal donors” respectively.
This implies that if the recipient be found to belong to Group I,
the blood of any donor may be transfused into his veins irrespective
of his group, and that if the donor be of Group IV, his blood may
be used for transfusion irrespective of the group of the recipient.
These statements may be accepted as true in an emergency, but
important reservations may have to be made under certain conditions.

It was at one time believed that the group reactions were clear-cut
and absolute rather than relative. At the present time, however,
the view is gaining ground that there may be some “over-lapping” of
groups, that is to say, a serum may contain agglutinins which give a
gross reaction with the corpuscles of one group and a reaction with
another group so slight that it can be detected only with difficulty,
or alternatively the recipient’s corpuscles may give a definite and
limited group reaction, while his serum may cause some agglutination
in the blood of a theoretically compatible group. These properties
have recently been termed “major” and “minor agglutinins” by Unger,
who claims that the possible presence of minor agglutinins makes it
advisable to test the recipient’s blood directly against the donor’s
in every case. The term “universal donor” commonly applied to Group
IV is, in fact, misleading. The blood of Group IV cannot be used
indiscriminately with complete impunity. The groups are determined by
the major agglutinins, and by these the ordinary gross reactions may
be eliminated. Everyone who has used blood transfusions extensively
has observed that slight reactions may occur after transfusion with a
compatible blood, irrespective of the methods employed. Usually these
reactions are slight, and do not in any way prejudice the benefits
conferred by the transfusion, but they may become greatly accentuated
in the later transfusions of a series, and it is probable that minor
agglutinins may be developed in certain pathological conditions.
Further reference to these phenomena will be made elsewhere (p. 93).
In addition to this, it has been commonly observed that the intensity
of the reaction varies greatly with the sera of different individuals
of the same group. It has also been stated by Stansfeld that the
agglutinating power of the serum of an individual may vary from time
to time. As a rule the corpuscles of a person belonging to Group I
are not agglutinated with equal rapidity or intensity by the sera of
Groups II and III, but the meaning of this phenomenon has not been
fully investigated.

A possible source of trouble will occur to anyone looking
critically at the table of reactions, for it will be noticed
that the serum of Group IV, the so-called “universal donors,”
agglutinates the corpuscles of all the other groups. How does it
come about, therefore, that the blood of this group may be given
indiscriminately? The answer is to be found in the fact that though
the reaction takes place as shown in the table _outside the body_,
nevertheless the serum of the transfused blood does not exert its
agglutinating power in the body of the recipient. Several hypotheses
have been advanced to account for this discrepancy, though no
final explanation has yet been arrived at. In the first place it
is possible that the agglutinating power of the serum is rendered
ineffective by the dilution which it undergoes when it is mixed with
the blood of the recipient. It has been shown, however, by Culpepper
that agglutination takes place outside the body with serum diluted up
to 1 : 150, a degree of dilution far greater than is ever obtained
in a transfusion where the dilution in the patient’s circulation
is usually no greater than 1 : 7. Secondly, it has been suggested
that the transfused plasma meets with an excess of plasma containing
protective or antihæmolytic properties. The evidence on this point
is conflicting. Hektoen in 1907 was unable to demonstrate any such
property in serum or plasma. Brem and Minot in 1916 both claimed
to have demonstrated antihæmolytic properties in serum, and Minot
added the observation that its concentration varies. Karsner in 1921
reported that he had failed to demonstrate anti-agglutinins in the
blood. For the present, therefore, the point must remain undecided.
Finally, it is possible that the agglutinins of the transfused
plasma, meeting with an excess of agglutinable cells, are all
absorbed without actually producing any agglutination. Whichever of
these hypotheses be true, the fact remains that the blood of Group
IV individuals may be given without serious effects in most ordinary
cases in which transfusion is indicated.

It must not be inferred from the tabulated reactions that a
transfusion with the blood of an incompatible group necessarily
produces a fatal, or even a serious, result. If, for instance,
an individual of Group II be transfused with blood of Group III,
the corpuscles of the donor’s blood will certainly be rendered
ineffective, being destroyed either at once or in the course of a
short time. But beyond this wastage of the transfused blood there
may be no effects as shown by morbid symptoms in the recipient; he
will merely not be benefited. There may, on the other hand, be an
evident reaction in the recipient, the symptoms varying from slight
discomfort to almost immediate death. It appears, therefore, that
there is a gradation of toxicity between the bloods of incompatible
groups, so that it may be justifiable owing to extreme urgency in
certain cases to perform a transfusion without doing any preliminary
tests on the bloods of donor and recipient. There is a good
chance that the groups will be compatible; if, however, they be
incompatible, there is still a good chance that the recipient will be
no worse off than he was before the transfusion.

Even when the tests have been performed, it may still happen
that through various causes a mistake has arisen. Owing to the
inexperience of the operator or to staleness of the sera used
in performing the test, an incompatible group may appear to be
compatible. It is necessary, therefore, that everyone who performs a
transfusion should be able to recognize the symptoms of a reaction
as soon as it begins to appear, so that the transfusion may be at
once discontinued. Sometimes the reaction between incompatible
groups is so immediate and severe that death takes place almost at
once. I did not myself perform any transfusions until after the
period when blood-grouping tests had become a routine procedure, so
that I have no personal experience of such unfortunate results. The
symptoms may therefore best be described in the words of one who
has several times witnessed the effects of an incompatible blood:
“The clinical picture of these reactions is typical. They occur
early, after the introduction of 50 cc. or 100 cc. of blood; the
patient first complains of tingling pains shooting over the body, a
fullness in the head, an oppressive feeling about the precordium,
and, later, excruciating pain localized in the lumbar region. Slowly
but perceptibly the face becomes suffused a dark red to a cyanotic
hue; respirations become somewhat laboured, and the pulse rate,
at first slow, sometimes suddenly drops as many as from twenty to
thirty beats a minute. The patient may lose consciousness for a few
minutes. In one-half of our cases an urticarial eruption, generalized
over the body, or limited to the face, appeared with these symptoms.
Later the pulse may become very rapid and thready; the skin becomes
cold and clammy, and the patient’s condition is indeed grave. In
from fifteen minutes to an hour a chill occurs, followed by high
fever, a temperature of 103° to 105°, and the patient may become
delirious. Jaundice may appear later. The macroscopic appearance of
hæmoglobinuria is almost constant.” (Peterson.)

In a fatal case recorded by other writers the chief symptom was
hæmoglobinuria, which progressively increased until the functions of
the kidney became so much interfered with by deposits of hæmoglobin
or damaged corpuscles that the patient died with suppression of urine
and all the signs of uræmia (25).

In other cases a slighter and transient hæmoglobinuria has been
noticed, showing that some destruction of red cells has taken place
without producing any further effects. This symptom is, of course,
due to hæmolysis following reactions between the serum and corpuscles
as explained above. The variation in degree of the reaction is to be
partly explained by the fact that there are three possibilities: (1)
The donor’s corpuscles may be hæmolysed by the recipient’s serum;
this will result in the transient hæmoglobinuria and wastage of the
transfused blood; (2) the recipient’s corpuscles may be hæmolysed
by the donor’s serum, or (3) serum of each may hæmolyse the other’s
corpuscles. Either of the latter events will be extremely serious.
As already mentioned, hæmolysis is always preceded by agglutination,
and it seems that the agglutination may be the more rapidly fatal of
the two. It was probably this that was chiefly responsible for the
suppression of urine in the case referred to, and a case has been
recorded in which it appeared to be the only cause of immediate death
or, as an American writer expresses it, “sudden exitus took out, out
of a clear sky,” owing to the presence of multiple emboli.

In addition to the evidence of hæmolysis the patient may exhibit
the symptoms described above. Sometimes the urticarial rash has
been accompanied by vomiting and headache. This group of symptoms
suggests that the condition is analogous to the anaphylactic shock
which may follow the intravenous injection of any foreign protein.
The symptoms in a mild degree do occasionally follow the transfusion
of blood which has been shown to belong to a compatible group, and it
had been found to develop even to an alarming extent after the later
transfusions, when a series was being given for a condition such
as pernicious anæmia (34). In such cases, however, as is suggested
elsewhere, this may, perhaps, be regarded as true anaphylactic shock.
The symptoms which may accompany a first transfusion cannot be
identical with this since true anaphylaxis must have been preceded by
sensitization with a minimal dose of foreign protein introduced into
the circulation.

It was formerly thought that possibly the products of hæmolysis were
themselves toxic and capable of producing the symptoms described.
This seems, however, to have been disproved by Bayliss, who has shown
that in the dog and cat the hæmolysed blood of the same species is,
with extremely rare exceptions, innocuous.

Another possible cause of similar symptoms is the sodium citrate used
as an anticoagulant in one of the methods of transfusion subsequently
to be described. But the symptoms, if due to this cause, will not be
accompanied by any signs of hæmolysis, are usually not severe, and
are always very transient. This will be referred to again later on.

The symptoms of incompatibility begin to be apparent so quickly that
the worst results can be avoided by the exercise of caution. If for
any reason it has been necessary to use an untested blood donor, the
first 100 cc. of blood should be injected very slowly. If no untoward
symptoms result, the remainder of the blood can be injected with
greater confidence. Little can be said as to the treatment of this
condition, for prevention is far better than cure. When the symptoms
have developed, the damage has been done, and cannot be undone. The
ordinary measures for combating severe collapse may be used.

A lesser danger of transfusion is that of administering the blood
too rapidly. Sometimes during a transfusion the patient complains of
difficulty in breathing and a sensation of tightness in the chest;
this should always be regarded as a warning that the blood must be
given more slowly or perhaps that enough has been given and that
the transfusion should be discontinued. Usually the symptom amounts
to nothing more than discomfort, and will disappear if caution be
exercised. The explanation is to be found in the too rapid filling
of the venous side of an impaired circulation with overloading, and
perhaps temporary dilatation, of the right side of the heart. I have
never seen these symptoms occur to an alarming degree, but actual
loss of consciousness with a very rapid and feeble pulse has been
recorded by other writers. Directions as to the amount of blood which
should be given and the rate at which it should be injected so that
these symptoms may be avoided will be found under the description of
methods given in a later chapter.



CHAPTER V

PHYSIOLOGY AND PATHOLOGY OF BLOOD GROUPS


In the foregoing chapter the reactions between the blood groups and
the morbid symptoms which may follow the injection of incompatible
blood have been described. In the present chapter some account will
be given of the more general physiology and pathology of the groups.

It seems to be clear that iso-agglutinins and iso-hæmolysins, that is
to say, serum reactions among the individuals of a species, are to be
found distributed widely through the animal kingdom. The phenomenon
is, however, weak in operation compared with that found among human
beings, and it is very much more difficult to demonstrate. The facts
have not been investigated for very many species of animals.

Some of the earliest attempts to investigate the distribution of
iso-agglutinins among animals were made by Hektoen in 1907. He tested
the blood of rabbits, guinea-pigs, dogs, horses, and cattle; his
results were negative in every case, but probably his technique was
imperfect or an insufficient number of animals was tested. Grouping
has been found among goats by Ehrlich. Ottenberg and others believe
that they have demonstrated the existence of three groups among
steers, and of four groups among rabbits. Von Dungern has shown
that there are four groups among dogs. Agglutination reactions were
found by Ingebrigtsen and by Ottenberg among cats, but they were
not constant, and it was not found possible to distinguish any
grouping. The same was found to be true of rats. I have not been
able to discover any record of research upon iso-agglutinins in
birds or reptiles. The phenomenon of blood groups has a possible
bearing on the success or failure of experimental transplantations
of tissue, whether healthy or diseased, from one animal to another
of the same species. From this point of view an investigation of
the blood reactions among mice was carried out by B. R. G. Russell
in the laboratories of the Imperial Cancer Research Fund, but he
was unable to find any sort of grouping. Ingebrigtsen has made an
attempt to correlate the results of the transplantation of arteries
in cats with their serum reactions, but he was unable to do so. His
results were equally bad whether iso-agglutinins were present or
not. Nevertheless, it is highly probable that the success of tissue
transplantation in man will be found to be largely dependent upon
compatibility of blood groups in donor and recipient. The problem
is one that cannot easily be investigated by experiment on animals,
among which natural incompatibility is evidently much less well
marked than it is in man. A method of overcoming this unsuitability
is suggested by the experiments of Ottenberg and Thalimer. These
observers, as already mentioned, found that in cats iso-agglutinins
were present, though inconstant; on the other hand, iso-hæmolysins
were seldom if ever found in normal cats, though they often
appeared in the recipients of transfusions. Grafting experiments
might therefore be preceded by transfusions designed to stimulate
artificially incompatibility of the tissue fluids.

The incompatibility of blood is essentially a phenomenon which
distinguishes different _species_ of animals, since in no case can
the blood of one species circulate unaltered in the blood-vessels of
another kind of animal. This serological specificity may be in some
way related to the sterility of one kind of animal with another,
though not actually causing it, and so be merely an incidental
phenomenon. It cannot be in any sense protective, since it never
happens in the course of nature that blood is transferred from one
animal to another. In the same way it is difficult to see how there
can be any biological “purpose” in similar differences between
individuals of the same species, and, so far as is at present known,
the possession of a particular group does not confer upon its owner
any advantage over the individuals of other groups, such as a
relatively greater immunity from disease, longevity, or fertility. It
is quite clear that there is no connexion between incompatible blood
groups and sterility between individuals.

An investigation of a possible relation between blood groups and
disease has been begun by W. Alexander at St. Andrews University. In
a preliminary communication concerning the blood groups found among
fifty patients suffering from “malignant disease” of all forms,
including leukæmia, he has found that there is a considerably higher
proportion of Groups I and III than among healthy people. On the
other hand, the groups are found in the normal proportions among
people suffering from tuberculosis, syphilis, and tetanus. It would,
however, be premature to assume that individuals of Groups I and
III are more liable to suffer from “malignant disease” than other
people, as the numbers tested are, at present, too small for definite
conclusions to be formulated. Also it remains to be proved that the
presence of malignant disease does not produce an alteration in the
agglutinating reactions by which the groups are determined.

It seems probable that the differences between the groups have arisen
incidentally in the evolution of mankind, possibly as the result of
the parallel descent of two or more original stocks from different
sources, which afterwards converged and mingled, with the production
of serological hybrids. In view of this it is of interest to find
that some investigation of the racial incidence of blood groups has
already been carried out. On the Macedonian front during the war a
large number of men of many different races were gathered together,
and scientific advantage of this opportunity was taken by L. and H.
Hirschfeld. The blood groups were determined in approximately 8,000
individuals, including French, English, Italians, Germans, Austrians,
Serbs, Greeks, Bulgarians, Arabs, Turks, Russians, Jews, Malagasies,
Senegal Negroes, Annamese, and Indians. According to the results
obtained by the Hirschfelds, the groups designated II and III show
a definite variation in their distribution among different races.
As will be seen hereafter, Group I is compounded of the two factors
producing Groups II and III, while Group IV results from their
absence. It is therefore necessary only to consider the incidence
of Groups II and III in calculating the racial differences. For the
statistical tables and diagrams the reader must be referred to the
original paper published in 1919, but the results may be roughly
summarized as follows. It was found that the factor producing Group
II is prevalent among European peoples, whereas the factor producing
Group III is characteristic of men from Asia and Africa. Thus the
Group II factor was found in not less than 45 per cent. among most
European peoples. It gradually diminishes in the countries lying
between Asia and Central Europe, being present in Arabs 37 per cent.,
in Russians 37 per cent., in Jews 38 per cent. In Asiatics and
Africans it falls considerably, being in Malagasies 30 per cent.,
in Negroes 27 per cent., in Annamese 29 per cent., in Indians 27
per cent. On the other hand, the factor producing Group III shows
exactly the opposite variation. Among the English, the most Western
people of Europe, it is rare, being found by these observers to be
present in only 10 per cent.; it rises to 14 per cent. in French and
Italians, to 18 per cent. in German Austrians, and to 20 per cent.
in the Balkan peoples. In Africa and Asia the Group III factor rises
considerably, being present in Malagasies 28 per cent., in Negroes 34
per cent., in Annamese 35 per cent., and in Indians 49 per cent.

We may still be far from elucidating the anthropological meaning
of these facts, for the mingling of the hypothetical stocks of
which mankind is made no doubt began in a remote antiquity, and
it is possible that a serologically pure race does not exist. The
investigation, however, of the more isolated peoples might throw much
light on the problems of anthropology.

Interesting as the wider questions may be, we are here more
immediately concerned with the distribution of the blood groups
amongst our own population. The percentages in which the four groups
occur have been estimated by various observers, and, as will be
readily understood from the foregoing remarks, the numbers show some
variation. The approximate figures as worked out by three observers
in America are as follows:

  ------+----------+---------------+----------------
        | Bernheim |     Moss      |   Culpepper
        |          | (1,600 tests) | (5,000 tests)
  ------+----------+---------------+----------------
    I   |     2    |      10       |    3 per cent.
   II   |    40    |      40       |   38  ”    ”
  III   |    15    |       7       |   18  ”    ”
   IV   |    43    |      43       |   41  ”    ”
  ------+----------+---------------+----------------

The percentages found among the first hundred men whom I tested in
the British Army in 1917 conformed almost exactly to the first of
these series of figures, and they may be taken as an average result
for Western peoples. It will now be seen upon what grounds it was
stated in the last chapter that the chances were in favour of the
blood of a donor chosen at random being compatible with that of the
recipient. If the patient belong to Group II, then 83 per cent. of
other bloods will be compatible. If he belong to Group III, 58 per
cent. will be compatible. Only if he belong to Group IV will the
chance in favour of compatibility fall below 50 per cent.

This statement of the facts concerning distribution of the blood
groups will serve to emphasize the absolute necessity for the careful
testing of a donor before his blood is used for transfusion. But,
further than this, it is necessary to clear away several widely
spread misapprehensions as to the group relations between an infant
and its mother and between the various members of a family. It has
several times been stated in print that a mother’s blood must be
compatible with that of her child, or sometimes that a baby has no
blood group, so that it may be safely transfused with blood taken
from its mother or its father without preliminary testing. On other
occasions the statement has been made that the brother or sister of
a patient is more likely than other people to belong to the same or
a compatible blood group, so that untested blood may be transfused
from one member of a family to another with little risk. Knowledge of
the existence of blood groups has become somehow mixed up with vague
popular beliefs concerning “affinities” and “blood relations.” Such
confusions must, however, be dissipated, for none of these statements
are more than partially true, and they may lead to a false sense of
security and to disaster.

The assertion that an infant has no blood group was tested by the
writer some time ago and shown to be false. On several occasions
a newly born infant was tested and found to show well-marked
agglutination reactions indicating Groups II or III as the case
might be. Even in 1905 it had been shown by Martin that reactions
could often be demonstrated between an infant’s corpuscles and the
maternal serum, and sometimes between the infant’s serum and the
maternal corpuscles. More recently (March 1920) the results of a full
investigation into the reactions found in infants and children have
been published by W. M. Happ in America. These researches began with
the testing of blood from the umbilical cord, and this was seldom
found to show the blood reactions as given by the adult. So far the
statement quoted above was justified. It is even true that the serum
of an infant’s blood will usually not give any reaction at birth
or during the first month. The percentage in which it does give a
reaction increases with the age of the child; after one year it is
usually, and after two years always, established. On the other hand,
the agglutination reaction in the corpuscles appears before that in
the serum, so that the grouping tested in this way may be present
immediately after birth, as I found to be the case. It is possible
that the grouping which first appears may afterwards be modified, but
any change which occurs is always by the addition of factors and not
by their subtraction; thus an apparent Group IV may become a Group
II or III, or an apparent Group II or III may become a Group I. It
is found that when a reaction is present in both the corpuscles and
the serum, the group does not afterwards change. Happ’s conclusion,
based on his investigations, was that it is unsafe to transfuse an
infant with its mother’s blood without first making the usual tests,
and the reasons for this will now be evident. In the first place an
infant _may_ be possessed of its final blood reactions very shortly
after birth, and should therefore be treated in the same way as if
it were an adult. In the second place, although its serum may be
without agglutinating powers, so that transfused corpuscles will
not be attacked, yet its corpuscles may be possessed of pronounced
agglutinophilic properties, so that they may be seriously affected
by the serum of transfused blood from an incompatible group. In
the third place, as will presently be seen, it is by no means the
rule that an infant should belong to the same group as its mother,
whatever its blood reactions may be.

Another set of observations, leading to precisely the same
conclusions, have been made by F. B. Chavasse of Liverpool. He terms
the potential agglutination of the fœtal corpuscles by the mother’s
serum, and of the maternal corpuscles by the serum of the fœtus, the
“maternal threat” and the “fœtal threat” respectively, and states
that there is no obvious relationship between the “fœtal threat” and
eclampsia or the toxæmias of pregnancy. The inference is therefore
justified that there is no transference of the agglutinating
substances in either direction across the placental membranes. No
chemical “immunity” is acquired, therefore, on either side, since
the protection is mechanical. This agrees with the fact observed
by Happ that the mother’s milk contains the same agglutinins as the
serum of her blood; but these do not have any deleterious effect
upon the infant, and are therefore either not absorbed at all or are
destroyed in the process of digestion.

The statement that the blood group of an infant is not necessarily
the same as that of its mother can be amplified, for it has been
found that blood groups are inherited on a definite plan, so that if
the groups of the parents be known, certain predictions can be made
as to the possible groups that may be found among their offspring.
Many characters in animals and plants have been shown during the last
twenty years to be transmitted according to the Mendelian plan of
inheritance, but up to the present time very few normal characters in
man have been isolated, and their manner of inheritance demonstrated,
though a number of pathological conditions have been shown to conform
to the theory. It is therefore of much interest to find that the
inheritance of blood groups in man can be quite satisfactorily and
consistently explained in Mendelian terms.

According to this theory, each quality in an organism which can be
isolated and investigated independently of other qualities, is termed
a “unit character,” and the appearance of each such unit character
is determined by the presence of something called a “factor” in the
sexual cells or “gametes,” male and female, by the union of which the
individual is formed. Further, these unit characters are believed to
occur in alternative pairs, and at first it was supposed that each
alternative pair consisted of “dominant” and “recessive” characters,
the second of which could only make its presence apparent in the
individual if the dominant character were absent. Subsequently
it was seen that the dominant and recessive characters need not
necessarily consist of two positive, though opposite, qualities,
but might better be regarded as consisting of the presence of a
character and its absence. To use a classical illustration of this
view, sweet peas may be classified into tall peas and dwarf peas. At
first the unit characters were taken to be tallness (dominant) and
dwarfness (recessive). Later this idea was modified, and it was said
that potentially all peas are dwarf, but to some is added a factor
producing tallness, this factor being absent in those that are dwarf.
To represent this idea more simply a conventional notation has been
used, according to which the large letters of the alphabet indicate
the presence, and the small letters the absence, of each factor.

In order to apply this theory to the case under consideration, it has
been suggested that two pairs of factors are concerned:

  A the _presence_ of the character producing Group II.

  a the _absence_ of the character producing Group II.

  B the _presence_ of the character producing Group III.

  b the _absence_ of the character producing Group III.

Each pair of factors is transmitted independently of the other. Both
A and B may be absent, in which case the individual belongs to Group
IV; or both may be present, and in this case the individual gives the
reactions of Group I.

It must be understood that the term “character producing Group II”
is here used as a convenient way of expressing the obscure and
probably complicated set of properties responsible for the reactions
manifested by individuals of Group II. It includes not only the
agglutinin or hæmolysin of the serum which reacts with corpuscles of
Group III, but also the complementary iso-agglutinin or iso-hæmolysin
by virtue of which the corpuscles react with serum of Group III.

The appearance of the different groups can now be further explained
in terms of the Mendelian theory. According to the conception of the
individual formulated by Mendel, each cell of the body contains an
ingredient derived from each of the sexual cells or gametes which
united at the moment of fertilization of the ovum by the spermatozoon
to form the individual. But when the adult in his or her turn forms
sexual cells or gametes, these ingredients separate again, half the
gametes containing one of the pair of factors, half containing the
other. This process certainly takes place during the rearrangement
of the nuclear substance or chromosomes at the cell divisions which
result in the formation of the ripe sexual cells. It is called the
“segregation of the gametes.”

In the present case the unit character producing Group II will be
first considered. As already explained, the factors concerned may be
called A and a, and the individual of Group II may be constituted by
AA or Aa, and the gametes, therefore, may contain either A or a, but
not both. The individuals resulting from the union of the gametes
derived from Aa adults may then be constituted in three ways--AA,
Aa, or aa. Similarly for the unit character producing Group III,
the factors concerned may be called B and b, and the individual of
this group may contain BB or Bb. The gametes then contain either B
or b, and the individual resulting from their union may again be
constituted in three ways--BB, Bb, or bb.

In computing the results, however, it must be remembered that most,
or perhaps all, people are hybrids, so that both unit characters
are present simultaneously, and all the factors must be taken into
account. It is easily seen that the gametes derived from a hybrid
individual must contain one of the following combinations:

  AB, Ab, aB, or ab,

and consequently the individuals formed from them must have one of
the following constitutions:

  AB--Ab, Ab--aB, aB--ab, ab--ab, AB--AB,
  AB--aB, Ab--ab, aB--aB,
  AB--ab, Ab--Ab.

This includes all the possible combinations that can result from the
chance union of the gametes, and it is now clear which blood groups
result from which combinations, if it be remembered that

  A is dominant to a,
  B  ”     ”     ” b,

and that

  Group I results from the _presence_ of both A and B.
    ”  II    ”      ”   ”      ”     ”  A only.
    ” III    ”      ”   ”      ”     ”  B   ”
    ”  IV    ”      ”   ”   _absence_  ”  both A and B.

  Thus Group I may be constituted by AB--AB.
                                     AB--aB.
                                     AB--Ab.
                                     AB--ab.
                                     Ab--aB.
      Group II may be constituted by Ab--Ab.
                                     Ab--ab.
        ”  III  ”  ”       ”      ”  ab--aB.
                                     aB--aB.
        ”   IV  ”  ”       ”      ”  ab--ab.

It now becomes evident what offspring may result from the union of
parents who have any of the above constitutions. Thus parents both of
Group I may have offspring belonging to any group according to which
of the five possible constitutions they possess. If the union be
represented by

  AB--AB × AB--AB,

then only offspring of Group I can result, since every gamete
contains both A and B. The other possibilities may be worked out by
the reader if he desire.

Similarly, a union of Groups I × II, I × III, or II × III may produce
any of the groups, definite limitations being imposed by the detailed
constitution of the parents. On the other hand, the remaining group
unions that are possible can only produce a more limited variety of
offspring. Thus II × II or II × IV can only produce Groups II or IV;
III × III or III × IV can only produce Groups III or IV; IV × IV can
only produce Group IV.

The Mendelian theory of inheritance in general has been subjected to
a prolonged and widely ramifying series of tests, and it seems in the
present state of knowledge to present a satisfactory and consistent
explanation of the facts. For a more extended account of it the
reader must be referred to the standard works on the subject.[6]
As regards its application to the present case, the test of actual
experiment has not yet been carried out on a large scale. A series
of observations has, however, been published by J. R. Learmonth,
who, taking forty families at random, determined the blood groups of
both parents and the children in each family. In this way he tested
most of the possible group matings, and, with a single exception,
the group inheritance conformed to the theory as set out above.
Additional confirmation of the truth of the theory is afforded by
the pedigree given on the page opposite. I have recently collected
this pedigree, which includes fifty-nine individuals belonging to
four generations, and it has not been published before. It will
give, perhaps, a more graphic representation of the facts than has
been conveyed by the brief summary contained in the foregoing pages.
It does not show any variation from the results that were to be
anticipated according to the theory.

The exceptional result obtained by Learmonth in one of his forty
families serves to emphasize the clarity of the theoretical
considerations. In this family parents both belonging to Group IV had
a child showing the reactions of Group I. There are three possible
explanations of this:

(1) The observations were at fault.

(2) The putative father was not the real father.

(3) The Mendelian theory of inheritance is wrong.

The Mendelian theory is established on so firm a basis that, in the
absence of more numerous exceptions, (3) may be rejected. There is no
reason for supposing that the observations were inaccurate, and we
are therefore brought to the conclusion that in such a case the child
is illegitimate.

[Illustration: Fig. 6.--PEDIGREE SHOWING INHERITANCE OF BLOOD GROUPS
THROUGH FOUR GENERATIONS. THE GROUP OF EACH INDIVIDUAL IS INDICATED
BY A NUMERAL. THOSE WHO WERE NOT AVAILABLE ARE REPRESENTED BY A O]

The conclusions which emerge from this structure of theory and fact
are obviously of very great clinical importance. It is now clearly
demonstrated that a mother belonging, say, to Group I, may give
birth to a child belonging to any one of Groups I, II, III, or IV;
her blood may not be used for transfusing her child without a grave
risk that the “maternal threat” may culminate in the death of the
child. The same applies to the possible relations between a father
and his child. Two brothers, again, may belong to Groups II and III
respectively. Even the blood of twins may be mutually incompatible,
except in the rare case of “identical twins,” who, it may be supposed
on theoretical grounds, would certainly belong to the same group,
though I am not aware of a case in which this has been put to the
test. As much care, therefore, must be exercised in testing the blood
groups of members of the same family before performing a transfusion
as would be taken before using a donor who is not related to the
patient.

The medico-legal importance of the facts concerning the inheritance
of blood groups is also evident, and, although this test has not yet
been used as a test of legitimacy, there can be little doubt but that
it will be so used in the near future. The information to be derived
from it is of a negative rather than a positive character. Thus the
occurrence of Group III blood in a child whose mother is of Group II
and putative father of Group I cannot be taken as a proof either of
legitimacy or the reverse. But if, as in Learmonth’s case, parents
both of Group IV have a child of Group I, or if parents both of Group
II have a child of Group I or III, then this may be taken as a proof
of illegitimacy.

There is not much experimental evidence concerning the effect of
various pathological conditions on the agglutination reactions of
the blood and serum. It has already been mentioned that there is no
proof that the possession of any particular blood group confers
upon its owner any special immunity from, or liability to, disease.
The numbers, investigated by Alexander in the communication referred
to on p. 81, are too small for the observation to be of much value;
it is also necessary, as a preliminary to any such research, to
demonstrate that there is no abnormal alteration in the reactions of
the blood of these patients. It is probable, indeed, that evidence of
this alteration in malignant disease already exists, for a reference
to it is to be found in Kolmer’s work on serum-therapy,[7] but I have
been unable to find a record of the investigation.

I possess, on the other hand, evidence that an alteration may take
place in some other diseases, such as pernicious anæmia and familial,
or acholuric, jaundice. Evidence for the former was provided
recently by a patient whose condition was typical, clinically, of
the last stages of the disease. Her corpuscles, tested with stock
sera, belonged to Group II, but her serum, tested directly with
the corpuscles of prospective donors known to belong to Group IV,
agglutinated these vigorously, so that a transfusion could not
safely be performed. The same phenomenon has been found by other
observers. In acholuric jaundice there is a progressive destruction
of red corpuscles in the patient’s circulation. This appears to be
connected in some way with an abnormal functioning of the greatly
enlarged spleen, since the destruction of corpuscles ceases almost at
once when this organ is removed. There seems to be, in addition, an
alteration in the blood reactions. In a case which I tested recently,
the patient’s corpuscles were quickly agglutinated by serum of Group
III, and he therefore nominally belonged to Group II. His serum,
however, when separated and tested against other bloods of known
groups gave, in addition to a rapid agglutination of corpuscles
belonging to Group III, a definite, though slower, agglutination
of corpuscles belonging to Groups II and IV, showing that it had
acquired abnormal properties.

It is possible that there are similar alterations of reactions in
other pathological conditions. The instances mentioned above suggest
that the serum is affected rather than the corpuscles, but further
investigations are needed. It is an observed fact that blood outside
the body soon develops the property of auto-hæmolysis. If blood
is drawn from a vein, put into a test-tube, and allowed to clot,
then after twenty-four hours or more the serum which has separated
from the clot begins to be tinged with hæmoglobin, even though it
has remained absolutely sterile. It appears, therefore, that the
serum develops a hæmolysin and the corpuscles the corresponding
iso-hæmolysin, the interaction of which results in the breaking up
of corpuscles. If this process takes place in normal blood outside
the body, it would not be surprising to find that it may also occur
abnormally inside the body. This actually happens in the condition
known as paroxysmal hæmoglobinuria. The pathology of the disease is
obscure, but it seems that a hæmolysin develops in the serum as the
result of cooling in the extremities and hæmolysis takes place when
the cooled serum is again warmed by being restored to the general
circulation. The presence of this hæmolysin in addition to the normal
hæmolysins has been demonstrated by Moss. It is possible that a
similar though less acute change takes place in acholuric jaundice.
Blood transfusion, therefore, is not likely to be efficacious in such
conditions, since the transfused corpuscles may be destroyed whatever
the apparent blood group of the patient. Some of the facts of
auto-hæmolysis have been recently investigated by Bond, but it is not
necessary to give the details here. He concludes that the development
of auto-hæmolysins, which are non-specific and independent of
the specific hæmolysins of the blood groups, has a biological
significance in the history of the red corpuscle, and is a product of
ageing. The biochemistry, however, of the process remains at present
entirely unknown.

The necessity for careful blood grouping in every case before
performing a transfusion has now been sufficiently emphasized, but
before proceeding to the description of the methods of choosing a
donor and of grouping, a possible danger must be mentioned which may
arise even when the blood groups are known. In the preceding chapters
references were made to the effects which have been observed to
follow repeated transfusions given in the treatment of a condition
such as pernicious anæmia. In such cases, although the groups were
ascertained, and the bloods were also tested directly against one
another without any incompatibility being detected, yet when the
third or fourth transfusion was given, symptoms of toxæmia followed,
sometimes with hæmolysis. The death of the patient has even been
hastened in this way. A very striking instance of this phenomenon,
which has been recently reported (278), will serve to bring home the
reality of the danger. A boy was transfused by the citrate method
with blood from his father, and this was followed only by a mild
febrile reaction such as is often observed. Eighteen days later a
second transfusion with blood from the same donor was performed, and
after 150 cc. had been given, a severe reaction resulted, which was
followed later by pronounced hæmoglobinuria. In this case the bloods
of donor and recipient had been tested against one another directly,
but this was not repeated, and the groups were not ascertained until
afterwards. Probably there was some error in the original test, for
it afterwards appeared that the boy belonged to Group I and his
father to Group III, so that there should have been agglutination
of the boy’s corpuscles by his father’s serum outside the body.
Nevertheless, Group I individuals have been called the “universal
recipients,” and no ill effects are usually observed whatever blood
be used for transfusing them. In the other cases already mentioned
a reaction followed the later transfusions, even when the donor and
recipient belonged to the same group. It appears that by repeated
transfusions the recipient becomes as it were sensitized to the
blood of another individual even of the same group, and consequently
great caution must be used in giving the later transfusions of a
series. Some light is thrown on this question by the observations of
Ottenberg, already referred to, concerning the artificial production
of iso-hæmolysins in cats. In these animals iso-agglutinins are
found, but iso-hæmolysins seldom or never. The reaction is, however,
found to become hæmolytic in the recipients of transfusions, and it
is then selective. It seems, therefore, that the group reactions
may not be as clearly defined as was at one time supposed. Probably
there are slight incompatibilities of an unknown nature between
individuals of the same or compatible groups. These are very seldom
of any consequence in a first transfusion, but become accentuated
as the result of “sensitization,” and in later transfusions have
a pronounced influence. This “over-lapping” of groups has been
mentioned on another page. It must not be supposed that any untoward
results follow repeated transfusions as a general rule, for usually
no such effect is observed. In order, however, to minimize the risk,
it may be suggested that the following precautions should be taken:
(1) The donor should be actually of the same group as the recipient,
and not merely of a theoretically compatible group; a patient, for
instance, of Group II should receive blood of Group II rather than
of Group IV. (2) The same donor should not be used for the later
transfusions of a series, on the grounds that the sensitization
appears to be an individual rather than a group phenomenon. (3) In
performing the later transfusions, the blood should be given at first
very slowly, so that it may be discontinued at the first appearance
of any signs of a reaction.



CHAPTER VI

THE CHOICE OF BLOOD DONOR


The physiology of blood groups having been examined, the principles
governing the choice of a blood donor can be more readily understood.
It is evident that this choice is determined largely by blood groups,
and in the present chapter therefore the clinical methods of testing
for the groups will be described.

Before, however, the bloods can be tested, a willing donor must
be found, and this is not always an easy matter. During the war,
even when transfusion was being practised on a large scale, there
was never any difficulty in finding volunteers among the men that
were more lightly wounded. In addition to the genuine and ready
response which many men would make at once to a call for help in a
matter of life and death, there was the glamour of novelty and the
feeling of satisfaction following an act of conscious heroism--for
such the sacrifice of blood was held to be, the days having long
been forgotten when as much blood was “let” in the treatment of
almost any ailment. In the Expeditionary Force, too, the unofficial
reward of a fortnight’s leave in England proved a potent inducement,
and the rejection of a volunteer on the ground of incompatibility
was regarded almost as an injustice or as a reflection upon the
physical condition of the candidate. In civilian life, however, such
inducements cannot be held out, and it will be found that many a
man “does not like the idea” of parting with a pint of blood, even
though the sacrifice may save another’s life. Often, however, a
near relative of the patient may happen to be willing and suitable,
or, failing this, in a hospital ward there will usually be some
young man who has been admitted for a slight operation, such as the
radical cure of a hernia, and will accede to a request for blood
if the procedure, its object, and its harmlessness to himself be
briefly explained. Notoriety is fortunately seldom a motive for
volunteering, and though paragraphs have occasionally appeared in the
daily press with headings such as “Police Inspector’s Sacrifice,”
this has probably not been done by the donor’s own wish. It is, after
all, natural that to the mind of a layman the giving to another of
so personal a possession as his blood should seem to be an act of
heroism, and it is also natural that occasionally a man should feel
some repugnance to taking part in a strange performance which he but
dimly understands. To the young, on the other hand, the procedure may
appeal by its faint flavour of adventure.

Occasionally during the last two years advertisements for blood
donors have appeared in newspapers, probably not in vain. If the
demand for blood donors becomes greater than it has been as yet, it
will certainly result in the creation of a class of “professional
blood donors,” who already exist in some numbers in the United States
of America, where blood transfusion is a more widely recognized form
of therapeutics than it is in this country. These professionals have
even formed a Trade Union, so that as high a fee as possible may be
obtained from those who need their blood. Apart from this, some of
the advantages of having these professionals available have already
been explained in the chapter on the dangers of blood transfusion.
It is evident that certain sources of danger can be eliminated in
advance, and in an emergency it is obviously better to have donors
of known groups available, so that no time is lost in testing the
prospective donors of whom several in succession may be found
unsuitable. Probably it will be easier for practitioners to arrange
for such professionals to be available at the shortest notice than
for necessary arrangements to be made in a hospital. Even in large
institutions it is usually difficult for any of the men employed in
them to be spared from their work for twenty-four hours, so that,
although suitable men of known groups are always within call, it may
be impossible to use them. This, however, is not the place to discuss
the organization that is necessary to make a blood transfusion a
really efficient form of emergency treatment in a hospital. It may
merely be observed that in every hospital it should be possible
to give a blood transfusion to a patient suffering from urgent
hæmorrhage within fifteen minutes of his arrival on the premises.

Whether the donor be a “professional” or an “amateur,” it may be
useful to mention a few points to be observed in choosing him. There
can be no doubt that the most satisfactory individuals for the
purpose are young men between the ages of eighteen and twenty-five.
The younger the donor, the less likely is he to be suffering from
certain of the diseases mentioned in the chapter on the dangers, the
less will be the immediate effect of the withdrawal of circulating
fluid, and the more quickly will he recuperate from the loss of blood.

It must not be supposed, however, that the withdrawal of even 1,000
cc. of blood will usually have an appreciable effect upon a healthy
man. It is impossible to predict from the donor’s appearance what
immediate effect the loss of blood will have upon him. It sometimes
happens that the most robust-looking individual becomes faint after
losing a few hundred cubic centimetres, whereas another, to all
appearances pallid and much less satisfactory, will not evince the
slightest discomfort from the loss of 750 cc. or even more. Normally
a man should be able, by his physiological mechanisms, to compensate
reflexly and at once for the removal of this amount of fluid from
his circulation. In any case, the worst effect that is seen in a
well-chosen donor is a transient faintness; it is usually wise to
keep him on his back for two or three hours after the operation, and
he should not, if it can be avoided, return to his work on the same
day. During the late war a medical officer of my own acquaintance
gave 750 cc. of blood for a severely wounded friend and continued
his arduous duties as Surgical Specialist in a Casualty Clearing
Station immediately afterwards. In this case, however, the donor was
solely responsible for his own welfare; usually this responsibility
rests upon another, and greater care must be exercised. The effect,
indeed, of a transfusion upon the donor seems to depend more upon
psychological than upon physiological factors. A nervous and
excitable donor is more likely to suffer than one who approaches the
operation without apprehension. This is another point in favour of
employing a professional donor, who soon becomes familiar with the
whole procedure and will lose all symptoms of fear.

The same considerations may be applied to the use of women as blood
donors. In them the spirit of self-sacrifice is commonly more highly
developed than it is in men, and some of the most eager donors will
be found among them. The disability of nervousness will, however,
occur more often in women, and another consideration of importance
is that the veins of a woman are usually much less easily accessible
than those of a man. Not only is the abundant subcutaneous fat an
impediment in women, but usually the superficial veins are all of
small size. The method of choice for performing a blood transfusion
will be presently described, and it will then be seen that the
operation is easier and that much less damage is inflicted on the
donor if a large superficial vein can be tapped. In women this will
very often be difficult or even impossible. In general, therefore, it
may be stated that the use of women as blood donors is to be avoided.
The fallacies concerning the indiscriminate transfusion of an infant
with its mother’s blood and of any patient with the blood of a near
relation have already been explained.


TESTING FOR BLOOD GROUPS

Reference to the table of blood reactions given on p. 71 will show
that in order to discover the blood group of any individual it is
only necessary to test his corpuscles against the serum of Groups II
and III. These reactions may be recapitulated as follows:

  (i) If he be Group I, his corpuscles will be agglutinated by the
  serum of Groups II and III.

  (ii) If he be Group II, his corpuscles will be agglutinated by the
  serum of Group III only.

  (iii) If he be Group III, his corpuscles will be agglutinated by
  the serum of Group II only.

  (iv) If he be Group IV, his corpuscles will be agglutinated by
  neither serum.

Only the serum, therefore, collected from people known to belong
to Groups II and III need be kept in stock. This can generally
be obtained from the Lister Institute, and if kept sterile will
retain its agglutinating properties for some months, but under no
circumstances should serum more than six months old be used, since
the consequences of a failure to agglutinate may be very serious.
Nevertheless, the agglutinins contained in serum are very resistant
to physical and chemical changes in their environment. Dried serum
has been successfully used for testing purposes, and Culpepper has
shown that the reactions are not interfered with by cold or by
heat until actual coagulation of the serum takes place. Bacterial
contamination does not affect the reactions, so that the serum is
still active even when putrid. Various methods have been used for
preserving the serum. Its properties are not affected by the addition
of dilute cresol (1 : 250) or of chloroform.

In the absence of any stock sera, the agglutinating test may be
applied directly. A few cubic centimetres of blood are taken from
the patient, and the serum as soon as it has separated is tested
against the corpuscles of the prospective donor. If agglutination
occurs, this donor is at once excluded. If no agglutination occurs,
he is either of the same group as the patient or belongs to a
compatible group. Supposing that a donor actually of the same group
as the patient is wanted, then the reverse test must be performed
in addition, that is to say, the corpuscles of the patient must be
tested against the serum of the donor. If both tests are negative,
then donor and patient are proved to be of the same group. The method
of direct test cannot be applied in an emergency owing to the loss of
time involved; it is better, therefore, that anyone who intends to
be ready to perform a blood transfusion should always have serum of
Groups II and III immediately available.

The collection of stock sera is not a matter of any difficulty. With
strict aseptic precautions 20 cc. of blood are withdrawn in a syringe
from persons known to belong to Groups II and III; the bloods are put
into a sterile test-tube and allowed to clot. As soon as the serum
has separated it is drawn up into sterile glass bulbs of suitable
capacity, which are sealed off at each end. The most convenient
form of storage for actual use is a capillary glass tube sealed at
each end. Each tube may be made to hold a single drop, which is the
amount used for a test. There is then no wastage of serum, and no
chance of contaminating the remaining stock. When the blood has been
withdrawn and has clotted, the complete settling of the corpuscles
can be hastened by the use of the centrifuge. If the serum be left
in contact with the corpuscles for more than twelve hours, some
auto-hæmolysis may take place, so that the serum will become tinged
with hæmoglobin. It is exceedingly important that the two stock sera
should not become confused, and this may easily happen unless each
tube has some distinguishing mark.

The methods of testing for blood groups have been simplified by
successive observers since the existence of the groups was first
demonstrated in 1907. Moss used an elaborate technique such as was
essential for putting a new discovery upon a secure scientific basis.
In order to obtain a suspension of corpuscles, blood was drawn into a
syringe containing a solution of sodium citrate to prevent clotting.
The corpuscles were collected by means of the centrifuge, and were
thoroughly washed twice in normal saline solution so that they
were finally collected free from serum and from citrate. Serum was
collected in the manner already described. A series of small tubes
was then filled with equal quantities of serum and the suspension of
corpuscles, and was incubated for two hours at 37·5° C. At the end of
this time observations were made and again after the tubes had stood
for twelve hours in an ice chest. Varying degrees of agglutination
and hæmolysis were then accurately recorded, and far-reaching results
were obtained.

Later workers had the advantage of using stock sera belonging to
known groups, so that the number of observations to be made was very
greatly reduced. Brem introduced in 1916 a method of testing in
which he mixed the serum and suspension of washed corpuscles in very
small quantities on a coverslip, which was inverted over an ordinary
cell slide rimmed with petroleum jelly. The results could then be
observed macroscopically or under the microscope, and the presence or
absence of agglutination could be determined within fifteen minutes.
The detection of hæmolysis by the hanging drop method requires that
the cells should be incubated and observed at intervals for several
hours, but it is not always easy to see the disintegrated corpuscles
unless the process has taken place extensively. The diagram on p. 105
gives in a tabulated form some idea of the appearances presented by
the corpuscles of the different groups when mixed with the stock sera
and observed in a hanging drop under a microscope. Agglutination must
be distinguished from the formation of rouleaux, which may be seen in
any of the mixtures.

For scientific purposes these very careful tests are necessary,
but it seems to be clear that for clinical purposes a much rougher
and quicker test is adequate. In the clinical determination of
blood groups it is superfluous to carry the test to the point of
watching for hæmolysis, for it is upon the presence of agglutinins
in the serum and the corresponding iso-agglutinins in the corpuscles
that the determination of the groups depends. Further, no error is
introduced by neglecting the hæmolysis, since it has been shown
that hæmolysis is invariably preceded by agglutination. It is the
occurrence of agglutination therefore that is of prime clinical
importance. If that is excluded, hæmolysis is necessarily excluded
also, and the prolonging of the test is seen to be only of academic
interest. In the methods described above the corpuscles were always
tested in the form of a washed suspension. This precaution was taken
on the supposition that the presence of any of the serum belonging to
the corpuscles might interfere with the reaction. If, however, the
amount of this serum be small relatively to the amount of the test
serum, then no such interference takes place.

[Illustration: Fig. 7.--TABULATION OF SERUM REACTIONS AS SEEN IN
HANGING DROPS.]

The ordinary clinical method of testing may therefore be greatly
simplified, and the one commonly used at the present time is as
follows: A single drop of each of the stock sera is placed on two
glass slides, or, better, side by side upon a white glazed tile or
plate, the numbers of the groups, II and III, being written above the
respective drops. The lobe of the ear of the person to be tested is
then washed with ether and pricked with a sterile surgical needle. A
small quantity of the blood which exudes is taken up on the end of
a blunt metal or glass rod, and is intimately mixed with the drop
of serum under the number II. The end of the rod is then carefully
wiped clean, and a similar small quantity of blood is mixed with
the drop of serum marked III. The amount of blood to be used should
not be so great as to make the drop of too deep a colour, which
may interfere with observation of the reaction, but it should be
enough to impart to it a very definite red tint. The slide or tile
is then gently rocked, so that some slight movement is imparted to
the drops, which are at the same time closely watched in a good
light. The agglutinating reaction is readily seen with the naked
eye, especially against the white background provided by the tile.
If the serum be properly active, the agglutination of the corpuscles
begins to be apparent as a definite granular appearance resembling
brick dust within a minute of mixing. With a little practice this
appearance is easily recognized, but it must be distinguished from
the appearance produced by a mechanical gravitation of the corpuscles
towards the centre of the drop. If agglutination is taking place, the
granulation appears simultaneously throughout the drop, and not only
in the centre. With an active serum the process may proceed rapidly,
so that in less than five minutes the corpuscles have been aggregated
into a few irregular masses; often it stops short of this, but the
drop presents, nevertheless, a coarsely granular appearance which is
quite unmistakable. If no granulation can be seen at the end of five
minutes, it can be assumed that the test is negative for the serum of
that group, and the group of the corpuscles may be deduced upon the
principles already explained.

The test carried out in this way is admittedly not susceptible of
the same finesse as if it were done with the assistance of the
hanging drop, the incubator, and the microscope; nevertheless, my own
experience in a large number of cases has shown that, clinically,
this test may be relied upon, and the same view has been expressed
by other writers on the subject. Very seldom is there any doubt as
to the presence or absence of agglutination. When doubt exists, it
is easy to repeat the test and obtain a confirmation of the result.
It may perhaps be urged that this test is quite insufficient for
eliminating the slighter degrees of incompatibility which have
produced serious results when the transfusion has been repeated
several times. But in the cases reported, the blood that was used
had not shown any agglutination even when most carefully observed
under the microscope. It seems, therefore, that the results were
probably due to another factor, as already suggested (see p. 57),
which the more elaborate test failed to eliminate. The efficiency of
the rapid test is therefore not invalidated. It is, nevertheless,
in the present state of knowledge, a wise precaution to perform
the direct test between patient and donor in addition to the group
test when circumstances permit. It is essential when the patient is
suffering from any form of blood disease. It is unnecessary when
the transfusion is to be performed as a life-saving operation in
hæmorrhage or shock.



CHAPTER VII

THE METHODS OF BLOOD TRANSFUSION


Some reference has already been made in the first chapter to the
rapid development in recent years of the technique of performing a
blood transfusion. The earlier operators, owing to the difficulties
introduced by the coagulation of blood outside the body, were
constrained to make use of some method of direct transfusion, the
blood flowing directly from an artery of the donor into the patient’s
veins. This has now been largely replaced by one of the methods of
indirect transfusion, the blood being withdrawn from the donor into a
vessel in which clotting is delayed or prevented, and then injected
or allowed to run into the patient’s circulation.


=Direct Transfusion.=--The obvious method of performing a direct
transfusion is by making an end-to-end anastomosis between an artery
of the donor and a vein of the recipient. The most readily accessible
artery is the radial at the wrist, and this is indeed almost the
only artery that is available. The most accessible vein is the
median basilic or the median cephalic at the elbow. The operation
of end-to-end anastomosis, using an artery of so small a calibre as
the radial artery at the wrist is usually found to be, is one of
great technical difficulty; this effectually prevented transfusion
from being used at all frequently. A modification has been used by
Sauerbruch and others, in which the end of the radial artery is drawn
into the lumen of the vein through a slit in its wall. A suture is
passed through the radial artery close to its cut end, and the needle
is then passed through the slit in the vein and out again through
the wall of the vein an inch or so higher up. Traction on the suture
then pulls the artery into the vein. The artery has meanwhile been
temporarily occluded by a clip, which is removed when the artery is
inside the vein, so that the blood can then flow from one to the
other. This is easier to do than the anastomosis, but, in addition to
the other objections to direct transfusion to be mentioned presently,
the difficulty occurs of occlusion of the artery by the physiological
process of inversion of its coats at the cut end. This is likely to
happen before much blood has passed, so that apparent success at
first is often not maintained. Sauerbruch claimed that the amount of
blood that had passed could be estimated by measuring the time taken
for 1 cc. of blood to flow from the artery before it was introduced
into the vein; but there is no proof that the rate of flow remains
constant.

If direct transfusion be desired, there can be no doubt that Crile’s
method, introduced some fifteen years ago, is the best to employ.
After much patient work Crile perfected a method of anastomosis
which ensures that no occlusion of the vessels can take place at the
site of junction. This depends on the use of a short silver tube,
through which the end of the artery is threaded. The artery is then
pulled back again outside the tube in the form of a cuff and fixed
in position. The end of the artery has thus been made rigid, and
over this the vein is pulled in its turn and fixed by a ligature.
A watertight junction is thus made, and blood can flow through it
without interruption--unless clotting takes place in the vessels as
the result of handling and injury to their walls. This method has
been extensively used in America, and it was the first to render the
operation of transfusion a comparatively popular one.

Various other devices for achieving the same result have been
elaborated by other workers, and attention may be drawn to those of
Elsberg and Bernheim, both of which are described in the book by
the latter on “Blood Transfusion.” During the war a simpler method
was introduced by Colonel Andrew Fullerton, who, working at a
Base Hospital in France, found that he could get good results by
employing a thin rubber tube with a small silver cannula at either
end. The apparatus was first coated on the inside with a thin layer
of paraffin wax, in order to discourage clotting within the tube,
and the cannulæ were introduced into the donor’s artery and the
recipient’s vein respectively. The blood could then flow freely
from one to the other. The fact that blood was being transmitted
was taken to be proved by the visible pulsation of the thin rubber
connecting-tube synchronously with the arterial pulsations. The
disappearance of this was assumed to be evidence that clotting had
occurred. This method was described by Colonel Fullerton to the
surgeons working at the Casualty Clearing Stations, where blood
transfusion was likely to be of most service, but it was never used
extensively. The coating of the inside of the tube with paraffin is
in itself an operation of some difficulty. Under conditions in which
any loss of time could not be permitted, success by this method was
not attained with sufficient certainty, and it was shortly afterwards
replaced by the more satisfactory methods described below. The most
recent work on direct transfusion has been done by J. M. Graham at
Edinburgh, who has however reached the conclusion that the technique
is always more difficult than that of indirect transfusion.

It can easily be seen, therefore, that all the known methods of
direct blood transfusion present great technical difficulty, which
renders the method unsuitable for general use. There are, in
addition, certain other objections to it of an obvious nature. It is,
in the first place, impossible to measure the amount of blood which
has passed from the donor to the recipient. Sometimes an indication
may be obtained from the evident improvement in the condition of the
patient, accompanied by the signs of loss of blood in the donor.
More often clotting takes place, unknown to the operator, at some
point, with the result that blood ceases to pass a considerable time
before the end of the operation, and the patient has consequently
received very much less blood than is supposed. It has been claimed
by Libman and Ottenberg that the amount of blood transferred may
be estimated by weighing the donor before and after the operation.
This presupposes that a very accurate weighing machine is easily
available, which usually is not the case.

A second objection is the extent of the injury which is necessarily
inflicted on the donor. His radial artery must be exposed through
an incision of considerable length, and must be ligatured at the
conclusion of the process. The operation becomes, therefore, a matter
of some moment to the donor, who will be permanently scarred, and can
under no circumstances be used for transfusion more than twice.

A third objection is that the transfusion cannot be done with due
regard to the condition of the patient. A delicate and difficult
operation has to be performed with the donor and recipient lying side
by side, their arms close together. It is therefore almost imperative
that both should be on operating-tables of a convenient height.
Often, however, with an exsanguinated patient it is very important
that he should not be moved from his bed, but as a bedside operation
direct transfusion becomes difficult indeed!

A final objection is that in some people the radial artery is of very
small calibre, so that when all preparations have been made, and
the artery exposed, it is found to be quite impossible to proceed.
Another element of uncertainty is thus introduced.

There is, therefore, little to be said in favour of direct
transfusion, and much to be urged against it. This method has,
indeed, in my own opinion, come to be of historical interest only.
For this reason the different methods have only been very briefly
described. For more detailed information, reference must be made
to the various original communications, which will be found in the
Bibliography.


=Indirect Transfusion.=--The methods of indirect transfusion may
be divided into those which depend upon the use of an anticoagulant
mixed with the blood and those in which the blood is given
unaltered. The technique of either process is simple compared
with that of direct transfusion, though any method which makes
use of whole blood can never be quite as free from uncertainty or
difficulty as one which introduces the use of an anticoagulant. If
the blood is prevented from clotting, the chief cause of failure
in performing blood transfusions is removed. With any whole-blood
method of transfusion speed is exceedingly important, frequent
practice is a very great advantage, and it is essential, as with
direct transfusion, that the donor and recipient should be in close
proximity to one another, if not actually side by side.

On the other hand, the use of an anticoagulant renders speed and
frequent practice of less account. The blood can be drawn, and can
then be put on one side until the best moment for giving it has
arrived. Due regard may be had to the patient’s condition, since the
blood can be carried about and can be given at leisure to the patient
in his bed without disturbing him and almost without his knowing it.
The donor, too, is not exposed to the mental shock of lying for some
time side by side with a patient who may be _in extremis_, or may
even expire during the operation.

There are, however, those who consider that the use of whole blood,
instead of blood which has been chemically treated, has advantages
which outweigh the possible disadvantages mentioned above. Two
methods of using whole blood are, therefore, described first; the use
of anticoagulants is then described in detail, and their advantages
and possible dangers are enlarged upon.


=Whole Blood Transfusion with Syringes.=--It is obvious that, if
blood can be drawn from the donor’s vein into a glass syringe and
injected into the recipient so rapidly that clotting has no time to
occur, then a transfusion of any quantity of blood that may be wished
can be given by this simple means. The measure of the amount of
blood transfused is given by the number of syringes that have been
filled and emptied. This method has been successfully used by several
workers, and it has the advantage that no very special apparatus is
necessary. It does, however, require that several syringes, and more
than one assistant, should be available, since clotting will take
place in the syringes, unless they be frequently washed out. There is
also the possibility that clotting may take place in the needle which
is introduced into the donor’s vein, since this cannot be withdrawn
and replaced for each syringeful of blood that is transferred. With
practice, however, and with good assistants, the process can be done
quickly enough to avoid this. Wide-bore needles with short rubber
connexions are introduced into the veins of donor and recipient;
if, as often happens, this is difficult to do through the skin in
the case of the recipient, his vein must first be exposed through
an incision and a glass or metal cannula introduced into it. The
operator then fills the syringes with blood in quick succession and
hands them to his first assistant, who injects the blood into the
recipient. Blood is prevented from escaping from the needles when
the syringes are disconnected by nipping the rubber connexions with
the fingers. The first assistant passes the empty syringes to the
second assistant, who washes them out with normal saline, and hands
them back if needed to the operator. This can be done with six 20 cc.
syringes used in rotation, possibly with only four.

The most recent description of this method has been published by
J. M. Graham of Edinburgh, who has introduced an improved form of
needle. This consists of a double tube; the inner tube has a needle
point which is used for puncturing the vein, and can be withdrawn
into the blunt outer tube when the vein has been entered. Any further
wounding of the vein is thus avoided. In addition, movement of the
needle-cannula is prevented by a bull-dog forceps attachment, which
is clipped to the skin. Graham finds it advisable to lubricate the
cannulæ and syringes with vaseline before being used. He also
states that: “As the absence of clotting depends upon the rapidity
with which the syringes are filled and emptied, a series of syringes
should be used in strict rotation, and all trace of blood must be
washed out with saline before the syringes are used again. One
or two additional assistants are necessary for this method.” The
disadvantages are evident, and it is not suitable for general use.

A modification of the method has been described by Unger, in which
only one syringe is used. The barrel of this is cooled by an ether
spray so that clotting is discouraged or prevented.


=Whole Blood Transfusion with Kimpton’s Tube.=--The principle of this
method depends upon the use of paraffin wax as a coating for the
vessel into which the blood is drawn, so that clotting is prevented
or greatly delayed. The form of the vessel has been modified by
different workers, but the essentials are the same in each. One form
of the apparatus, known as the Kimpton-Brown tube, is illustrated in
the accompanying diagram. It consists of a graduated glass cylinder,
of about 700 cc. capacity, the lower end of which is drawn out into
a cannula point at an acute angle with the body of the cylinder; the
point is of a size convenient for introducing into a vein and its
bore large enough to allow of a free flow of blood through it. Near
the upper end is a side tube to which a rubber tube can be attached,
and an opening at the top is closed by a rubber bung. An ordinary
rubber double-bulb bellows is the only other apparatus that is needed.

[Illustration: Fig. 8.--KIMPTON-BROWN TUBE]

The glass vessel is first sterilized in the autoclave, and then it
must be coated on the inside with a thin layer of paraffin wax.
The whole success of this method depends upon this wax coating
being absolutely complete right up to the tip of the cannula at
the bottom. If the tiniest area of glass be left exposed in the
cannula, the process will fail. The production of this perfect wax
coating used to be exceedingly difficult of attainment without very
frequent practice. The apparatus was first raised to exactly the
right temperature; sterile, melted paraffin was then put into it,
and distributed evenly over the surface, excess being allowed to
run out. The apparatus was then cooled down, and could be put away
in a sterile towel ready for use, great care being taken that the
lumen of the cannula was patent and not blocked with excess of
wax. A simplification of the process was introduced by the use of
a saturated solution of wax in ether. This solution is put into
the vessel, which must not be heated, and is made to run all over
the surface, excess as before being allowed to escape through the
lower opening. The ether quickly evaporates, leaving a very thin and
perfect film of wax over the surface of the glass. As before, it must
be ascertained that the lumen of the cannula is patent. The apparatus
is then ready for use.

The donor and recipient need not be lying close together, but they
must be in the same room. A vein is exposed in the arm of each by
dissection under a local anæsthetic. The operator then picks up the
vein with a pair of dissecting forceps, and makes an oblique cut into
the lumen as in the diagram on p. 131. A flap is thus made which is
held in the dissecting forceps in the left hand or is picked up with
a fine-pointed pair of artery forceps. The Kimpton’s tube is taken
in the right hand, and the point of the cannula is introduced into
the vein; that part of the lumen lying opposite the flap serves as a
gutter which guides the cannula directly into the lumen, so that it
is introduced without any fumbling or delay. The cannula is pushed
on so that its widest part engages the whole circumference of the
vein, forming a joint through which blood does not leak. The cannula
having been pushed well up into the vein, the forceps holding the
venous flap may be let go. At the same time an assistant grips the
donor’s upper arm, or some form of tourniquet of the necessary degree
of tightness is applied, so that the veins become congested without
obliteration of the arterial pulse. Blood now flows rapidly into
the tube, and the venous pressure is always sufficient to overcome
the counter-pressure of the increasing head of fluid in the tube. It
is unnecessary, therefore, to produce any negative pressure within
the tube with a reversed Higginson’s syringe or an exhaustion pump,
which has been used by some workers. Blood is allowed to flow into
the tube until the requisite amount has been obtained. The venous
congestion is then released, and at the same time the tube and
cannula, held at the lower end with the right hand in such manner
that the index finger is free, is withdrawn from the vein. At the
moment of withdrawal the end of the cannula is closed with the right
index finger. To prevent hæmorrhage from the donor’s vein, a ligature
previously put round it is tied by an assistant, or pressure on it
is maintained with a sterile swab. The operator must now, without
a moment’s delay, carry the tube filled with blood over to the
recipient. An opening in his vein is made by an assistant in the same
manner as already described, the finger is removed from the cannula,
and its point is instantly introduced into the vein. It is now
necessary to produce some degree of positive pressure in the tube to
ensure that the blood shall at once begin to flow steadily into the
vein. This is done with a rubber bellows, attached by an assistant to
the upper side tube, and the level of the blood in the tube should
at once begin to fall. Great care must be taken that the positive
pressure is released before the tube is completely emptied of blood
in order to avoid the obvious danger of the entry of air into the
patient’s vein. When the tube is nearly empty it is withdrawn, the
vein is ligatured, and the wounds in donor and recipient are sutured.
The most convenient pattern of Kimpton-Brown tube holds only about
500 cc. of blood, so that if more is needed, the process must be
repeated.

There is virtually only one cause of failure in transfusion by this
method, and that is the occurrence of clotting in the cannula or
at the bottom of the tube. If it does occur at any stage of the
operation, it cannot be remedied. It may happen when the tube is
nearly full; if so, the blood that has been withdrawn cannot be used.
Clotting may be due to an imperfection in the paraffin coating on
the glass, but if there is any delay from any cause, it may take
place independently of this. The method is therefore never absolutely
certain of success even in the hands of an expert, and for general
use it is certainly unsuitable. It was introduced into the British
Army by some of the American surgeons in 1917, and was used by the
writer under the guidance of Major Alton of the Harvard Medical Unit
during the first battle of Cambrai with good results. Many of the
English surgeons, however, soon abandoned it as a routine method in
favour of anticoagulants. There are other objections to it besides
its uncertainty. A vein must be exposed by dissection in both donor
and recipient, so that avoidable injury is inflicted on the former.
It is not a perfectly clean method, some blood necessarily escaping
at each successive stage in the process, though an expert can reduce
this to a minimum. In the hands of a novice it may occasion a very
bloody scene. The whole operation is one of urgency, and the best
interests of donor and recipient cannot always be considered.

Modifications have been introduced, such as that of Vincent, who uses
an attachment with a needle instead of the glass cannula point. This
obviates some of the objections, but introduces other difficulties,
such as the necessity for coating the inside of the needle with
paraffin wax. The technique can certainly be acquired, and the method
has rendered excellent service in the past, but it has no obvious
advantages except the uncertain one of avoiding chemical treatment of
the blood.


=Transfusion with Anticoagulants.=--It will have become evident from
the descriptions of the transfusion of whole blood already given, how
great a difficulty is introduced into the technique of these methods
by the physiological process of clotting in blood outside the body.
It is clear how much the process of transfusion would be simplified
if the clotting were to be prevented. Something has already been said
in the historical sketch of the various means by which this problem
was attacked, and it need only be stated here that the most suitable
substance for this purpose has been found to be sodium citrate. This
method was introduced by Lewisohn as recently as 1915, and it soon
became the method of choice among most of those who tried it.

The process of the formation of a blood clot has always been one of
the great problems of physiology, and numerous theories have been
propounded to explain it. The theory accepted at the present time
regards the process as a complicated one depending on the presence
in the blood of a number of different factors. This theoretical
explanation may be represented diagrammatically as follows:

[Illustration:

     Plasma                        Tissues and Platelets
      | \ \_______________             \          /
      |  \                \             \        /
      |   \                \             \      /
      |  Prothrombin      Ca Salts     Thrombokinase
      |           \_________   \       /
      |                     \   \     /
      |                      \   \   /
  Fibrinogen                 Thrombin
          \                     /
           \        ___________/
            \      /
             Fibrin
]

The clot consists of fibrin in which blood corpuscles are entangled.
It is clear that if any one of the reacting agents can be removed
or rendered inert the clotting cannot take place. There is only one
inorganic substance taking part in the reaction, and it is this
factor that is more easily removed than any of the others. Calcium
is precipitated in an insoluble form by various chemical reagents,
but it is obvious that for purposes of transfusion the formation
of an insoluble precipitate is not permissible. It is therefore
necessary to use a substance which will form a soluble compound with
the calcium and which is at the same time harmless when introduced
into the circulation. The only substance which has been found at
present to possess both these properties is citrate of sodium.
This forms with calcium a soluble double salt, in which calcium is
rendered inert. It is usually held that the calcium to be active
must be present in the ionized form, but recent investigations by
Vines into the rôle of calcium tend to modify slightly the accepted
view of its action. He has shown that calcium is present in the
blood in two forms, ionized and combined, and that both take part
in the coagulation reaction. He has, in addition, demonstrated that
a quantity of anticoagulant sufficient to combine with the whole of
the calcium present in a given quantity of blood is not enough to
prevent coagulation. It seems, therefore, that the anticoagulant acts
by combining with a large organic molecule of which calcium is only
one constituent, and not merely by combining with ionized calcium.
The organic complex with which the calcium is associated possibly
corresponds to the thrombokinase of the theory.

About the time that the use of the citrated blood was introduced
by Lewisohn, some investigations upon animals were carried out by
Salant and Wise in order to determine how sodium citrate was dealt
with and eliminated by the body. These observers found that it very
quickly disappeared from the circulation, nearly 90 per cent. of the
salt having been got rid of within ten minutes of its intravenous
injection. Part of the citrate is destroyed by oxidation, and the
rest, 30 to 40 per cent., is eliminated by the kidneys, the urine
being rendered alkaline. It was also shown that if a very large
dose was given, so large that toxic symptoms resulted, the effect
was rapidly obtained; but that if the toxic dose were not fatal,
no remote effects followed. Its injection never resulted in any
albuminuria.

Lewisohn showed by experiment on the human subject that up to 5
grammes of sodium citrate in the form of a 0·2 per cent. solution
could be injected intravenously without any harmful results. It
was also shown that this concentration of the salt was sufficient
to prevent clotting outside the body, and that the microscopic
appearance of the blood cells was not altered by the admixture of
this solution.

Theoretically, therefore, the amount of citrate that should be used
as an anticoagulant should be 2 grammes for 1,000 cc. of blood, or
100 cc. of 2 per cent. solution for 900 cc. of blood. In practice it
is better to err on the side of safety and to use a slight excess of
citrate. This amount of citrate should be used for the 750 cc. of
blood which constitutes the ordinary maximum amount of blood used in
a transfusion. For smaller quantities of blood the amount of citrate
may be correspondingly reduced.

The use of citrated blood was introduced to the British Army in
France in 1917 by Oswald Robertson, who recommended the use of a
larger amount of citrate than this. His object in increasing the
amount was to produce a solution which, when diluted with the correct
amount of blood, would be isotonic with it. It was thought that a
hypotonic solution might result in some damage to the red corpuscles
by osmosis, and Robertson therefore recommended the use of 160 cc.
of a 3·8 per cent. solution of citrate, which, when mixed with 750
cc. of blood, will give a solution of which the osmotic pressure
equals that of 0·9 per cent. saline solution. It may be doubted,
however, whether this consideration is of more than theoretical
importance. There can be little doubt that in practice the effect
of a slightly hypotonic solution, such as is given by the 100
cc. of 2 per cent. solution of citrate, is negligible as regards
destruction of corpuscles. If, however, it be thought necessary, an
isotonic solution may be produced by the addition of sodium chloride.
Other considerations, as will be seen shortly, weigh in favour of
giving the smaller amount of citrate. The dosage to be recommended,
therefore, on practical and experimental grounds is 2 grammes of
citrate in 100 cc. of water for 900 cc. of blood, or 1 gramme of
citrate in 50 cc. of water for 450 cc. of blood or less. These
proportions need not be observed very accurately. Latitude may be
used in either direction without harming either the transfused blood
or the patient.

It has been stated above that sodium citrate introduced into
the circulation in small quantities, such as are sufficient for
anticoagulant purposes, is non-toxic to man. In the light, however,
of the extended experience of the last four years, it is seen to
be possible that this statement may not be quite literally true.
Probably there is an individual variation in the tolerance of
different people to sodium citrate. Certainly in some cases a
reaction follows the injection of citrated blood. The symptoms of
this reaction are a slight headache, a rise in temperature to two or
three degrees above normal, sometimes accompanied by a rigor or a
sensation of chill, and an increase in the pulse rate. The effect is,
however, always very transitory, lasting only two or three hours, and
is never, in my own experience, attended by any symptoms which need
give rise to anxiety for the patient’s welfare; nor does it in any
way prejudice the therapeutic results of the transfusion.

That the reaction is caused by the citrate and not by another
constituent of the transfused blood has been believed by several
observers. In a case seen by the writer a slight citrate reaction
occurred in a youth who acted as blood donor. The transfusion was
carried out by a modification of the syringe method, which involved
the injection at intervals of a syringeful of citrate solution into
the donor’s circulation. The possibility that the reaction was
produced by another factor was therefore not present in this instance.

Nevertheless, it must be admitted that citrate has not yet been
absolutely proved to be the cause of this slight reaction in all
the cases in which it occurs. Evidence has, indeed, been brought
forward by Lewisohn and by Meleney to show that citrate is definitely
not responsible for the reaction. The statement is made that some
reaction occurs after 10 per cent. of all transfusions, and that this
percentage is unaffected whether whole blood or citrated blood is
used. Lewisohn has himself investigated the effects in a long series
of parallel cases in which different methods were employed, and he
reports that the results following the use of citrated blood were as
good as with any other method. Drinker states that reactions follow
the use of citrated blood slightly more often than they do that of
whole blood, but this has not been confirmed. He was unable to find
any impurity in the citrate that might be held responsible. It is
quite possible that all the reactions observed are in reality caused
by the “minor agglutinins” mentioned on p. 73. Meleney has noticed
that the blood of some donors is more likely to produce a reaction
than that of others; this suggests that the responsibility rests
with the blood and not with the citrate. The occurrence of a toxic
reaction constitutes the only real objection to the use of citrated
blood that has yet been brought forward, but even this has not yet
been fully substantiated; in any case, the reaction is of so little
importance that it is greatly outweighed by the numerous advantages
that are conferred by the use of citrate. The possibility that a
citrate reaction does sometimes occur may be taken as an indication
in favour of using the smaller amount recommended by Lewisohn rather
than the larger dose used by Robertson. The experience of a great
many observers has established the fact that citrated blood is quite
as effective as whole blood in its therapeutic effects.

It is convenient to have the sodium citrate in a form ready for
immediate use. I have therefore been in the habit of keeping it
in the solid form in small stoppered bottles, each containing 1
gramme of the salt. These are sterilized at 130° C., and can be
kept indefinitely until wanted. If 450 cc. of blood or less are to
be drawn, the contents of one bottle is shaken into the transfusion
flask; 50 cc. (approximately 2 oz.) of sterile warm water are added,
in which the citrate will rapidly dissolve. If more than 450 cc. of
blood is to be used, the contents of two bottles must be dissolved in
100 cc. or 4 ozs. of water. Alternatively a concentrated solution of
citrate may be kept in sealed ampoules, but the salt is less stable
in solution, and I prefer to keep it in the solid form.

The ideal method of blood transfusion seems to me to require that
it shall be absolutely certain of success, that the blood shall
not necessarily be injected into the patient immediately it has
been drawn, so that other circumstances besides the demands of the
transfusion operation can be considered, and that no injury shall be
done to the donor beyond the puncturing of a vein. In addition to
this, the method should be so simple and free from special apparatus
that it can be easily learnt and carried out by one operator without
skilled assistance. All these requirements are fulfilled by the
citrate method, and a satisfactory method of performing this will
next be described. As will be seen, the blood can be drawn with the
minimum amount of injury to the donor; when drawn, it can be put
on one side, for several hours if necessary, and then given to the
patient at whatever may be judged to be the most favourable moment;
the whole process can be carried out by a single operator without
any assistance; and finally, but little practice is needed to make
success certain every time.

The transfusion apparatus known as “Robertson’s bottle,” first
described by Oswald Robertson in 1918, is the basis of most citrate
methods. This could be easily improvised in a field laboratory, and
was extensively used during the last year of the war. The apparatus
consisted of a glass bottle of about a litre capacity, the mouth
of which was closed by a rubber bung. Through the bung three glass
tubes passed. One, connected by a short rubber tube with a wide-bore
needle, ended about an inch from the bottom of the bottle; through
this the blood flowed into the bottle. A second tube, which reached
to the angle between the side and the bottom of the bottle, was
connected by a rubber tube with a cannula; through this the blood was
injected into the patient. The third tube reached only just beyond
the bung, and to this was attached a Higginson’s syringe, by means of
which either negative or positive pressure would be produced inside
the bottle, according to which end of the syringe was attached.

It is unnecessary to describe this apparatus any further, for it was
found by myself and others that it could be with advantage modified
in the direction of simplicity. It is in the first place unnecessary
in drawing the blood to create any negative pressure if a needle of
a large enough bore (2 or 3 mm.) be used, and, further, it is an
advantage not to have the needle attached in any way to the bottle,
which, as the blood flows into it, has to be freely agitated in order
to mix the blood quickly with the citrate. The needle may, therefore,
be attached to a rubber tube of suitable length which hangs freely
into the collecting vessel as shown in the diagram on p. 127. The
third tube of “Robertson’s bottle” may be dispensed with by using a
conical flask provided with a side tube to which a rubber bellows
can be attached. The delivery tube is therefore the only one that
need pass through the rubber bung. This tube should have an angle in
it inside the flask so that its lower end reaches into the corner,
and the extremity should be ground down obliquely so that, although
it reaches right into the corner, it does not become occluded by
too accurate contact with the surface of the vessel. By this means
any wastage of blood is prevented. I have found it a very great
convenience to introduce into the delivery tube just outside the
flask an air-lock,[8] the value of which will be seen shortly. To the
barrel of this air-lock a rubber tube with a cannula is attached.
Close to the cannula is some form of clip. The whole apparatus is
illustrated in the figure on p. 133, and with the help of this its
use may be readily understood.

[Illustration: Fig. 9.--TRANSFUSION NEEDLE (ACTUAL SIZE)]

The particular form of needle which I have been in the habit of using
is shown in the figure. Its lumen has a diameter of 2 mm., and the
steel tube ends off flush with the wide shoulder to which the rubber
tube is attached. This avoids any recess within the needle in which
clotting may begin. The point of the needle should not be too long,
in order that it may not wound the opposite side of the vein when it
has been introduced. For ease of introduction, however, the extremity
should be very sharp and should have cutting edges. The point and
edges should be touched up on a bevelled hone each time before the
needle is used. The needle should be kept ready for immediate use
in liquid paraffin. I have found that the most convenient way of
keeping it is to put it into a test-tube containing paraffin, which
is plugged with cotton-wool and sterilized at 130° C. in the hot
air oven or by careful heating over a flame. In this way the needle
may be kept ready for an indefinite time without any chance of its
rusting. When it is taken out of the test-tube, a sterile rubber tube
is slipped on to it and it is then ready for use. As an additional
precaution, a small quantity of paraffin may be drawn up into the
rubber tube, which is thus lubricated on the inside, but this is not
absolutely necessary. The tube must be sterilized with the rest of
the apparatus, as rubber is destroyed by liquid paraffin.

[Illustration: Fig. 10.--DRAWING BLOOD FOR TRANSFUSION]

When the donor’s arm has been congested by gripping it above the
elbow, or better by the application of a tourniquet[9] drawn to the
requisite degree of tightness, a suitable vein, usually the median
basilic, is chosen. The area of puncture is washed with ether and
a very small quantity, 2 to 3 minims, of 2 per cent. novocain is
introduced over the vein with a hypodermic syringe. If a larger
quantity is used, the vein may become obscured, but this small amount
may be dispersed by a few moments’ pressure with the finger, and is
usually enough to anæsthetize the very small area of skin that is
to be operated upon. A tiny cut in the skin is then made with the
point of a scalpel, and the needle is pushed through into the vein.
If the donor’s vein is a large one, such as is usually found in the
type of donor recommended in a previous chapter, this is quite easy
to do. To make it equally easy if the vein be smaller, it has been
suggested by Watson that the vein may be fixed by pushing an ordinary
fine sewing-needle through the skin at right angles to the line of
the vein, into the vein, and out again through the skin. This needle
is held with the forefinger and thumb of the left hand, while the
right hand pushes the transfusion needle into the lumen of the vein
just below it. When the needle is in the vein, the blood flows out
rapidly through the tube which hangs into the flask containing the
citrate, as illustrated. This flask is held by an assistant, who
mixes the blood with the citrate by gently swinging it. If a properly
adjusted tourniquet is kept on the donor’s arm while he works his
forearm muscles by clasping and unclasping his hand, a flow of blood
is obtained which is fast enough to prevent clotting in the needle,
and indeed is quite as fast as most donors can tolerate. Blood up to
1,000 cc. may be collected in this way in ten to twenty minutes. If
the vein be of a good size, it makes no difference whether the needle
be inserted towards the heart or away from it. When enough blood has
been collected, the tourniquet is removed, the needle is withdrawn,
and pressure is maintained with a sterile swab over the site of
puncture for a few minutes. No further bleeding will take place after
this, and no suture is needed. The donor’s part in the operation is
then finished. He should be made to lie on his back for a few hours
afterwards, and given plenty of fluids, but beyond this no special
precautions are necessary.

When the blood has been drawn, and has been satisfactorily mixed with
the citrate, the flask may be put on one side until it is wanted, its
mouth having been closed with a cotton-wool stopper. If the blood is
wanted at once, the flask may be stood in a basin of warm water to
keep it at body temperature. Otherwise it may be allowed to cool, and
can be warmed up again when it is to be administered. The citrated
blood may be kept for a considerable time without undergoing any
appreciable change in its therapeutic value. It has been given twelve
hours or more after being taken with the same good effects as if it
had been newly drawn. During the war advantage was taken of this fact
to anticipate during quiet times the necessity for many transfusions
during times of stress. The blood was drawn in some quantity and kept
for several hours in an ice chest, so that it was readily available
during the expected battle. Recently I have administered to a woman
who had been operated upon for a ruptured ectopic gestation 600 cc.
of citrated blood which had been kept for twenty-seven hours at
room temperature after it was drawn. The effect was in every way as
satisfactory as if it had been freshly drawn, and there was no sign
of any toxic reaction. So far as I know, blood had not ever been kept
so long as this before being used, but there does not seem to be any
objection to so doing.

When the blood is to be given, the delivery tube with the rubber bung
is inserted in the flask, and the corpuscles which have gravitated to
the bottom are distributed again through the fluid by gently shaking
it. In administering the blood, it is very often advisable to inject
it through a cannula which is tied into a vein. If the patient is a
woman, it will usually be found that the veins are small and buried
in fat. Also many transfusions will be given to combat the collapse
due to shock and hæmorrhage, in which case the veins will be empty
and the use of a cannula will be found essential. Sometimes, however,
the patient will have large veins which can be readily distended;
this may sometimes be encouraged by keeping the arm for half an hour
beforehand in a bath of hot water. Under these circumstances the
blood can be given through a needle introduced in exactly the same
way as has already been described in the case of the donor. In the
following account of the process it will be assumed that the use of a
cannula is necessary.

When choosing a vein in the patient, the operator must be guided
by circumstances. Usually the median basilic will be the most
convenient, and if, in a collapsed patient, this is invisible,
previous knowledge of the position of the vein must determine
the site of the incision. If another operation is being done
simultaneously upon the upper part of the patient’s body, it may
be more convenient to use the internal saphenous vein in Scarpa’s
triangle, or even one of the superficial veins about the ankle. In
administering blood to an infant, several methods have been used.
These are described separately at the end of the present chapter.

[Illustration: Fig. 11.--TRANSFUSION CANNULA (ACTUAL SIZE)]

Whatever vein be chosen, the line of the incision is first
infiltrated with a small quantity of a 2 per cent. solution of
novocain. The vein is then dissected out, and is ligatured near the
lower end of the incision. A ligature is also put loosely round
the upper part. The operator now takes the barrel of the air-lock,
which, together with the attached rubber tube and cannula, is filled
with 0·9 per cent. saline solution, all air bubbles being carefully
excluded. The tube is clipped near the cannula, so that the whole
system, including the cannula, remains filled with the fluid. The
form of the cannula used will depend upon the operator’s particular
preference, but a type which I have found very convenient is shown
in the accompanying figure. It is made of glass, and its extremity
is ground down at an angle, which makes it very easy to introduce
into the vein. The slight constriction near this end ensures that
it can be securely tied into the vein and that no leakage round it
shall occur. This is very necessary, because there is sometimes a
considerable pressure to be overcome, due to venospasm in a collapsed
patient, before the blood begins to flow.

An oblique cut is now made in the vein, as shown in the
illustration, the cannula is introduced, and the upper ligature is
tied.

[Illustration: Fig. 12.--INSERTION OF THE CANNULA IN A VEIN]

The barrel of the air-lock, with its contained saline solution,
is then fixed firmly on to the rubber bung, so that the nozzle of
the delivery tube projects into the saline solution. Meanwhile, an
assistant has fixed a rubber bellows on to the side tube of the
flask; a short piece of glass tubing loosely packed with cotton-wool
should be interposed between the bellows and the flask to prevent any
particles of dust being blown over into the flask from the bellows,
which is not sterilized. The clip near the cannula is released, and
some positive pressure is produced inside the flask by means of the
bellows. The citrated blood then rises in the delivery tube, and
a corresponding quantity of saline solution is displaced from the
air-lock into the patient’s circulation. The blood then flows from
the nozzle of the delivery tube into the air-lock, and the remainder
of the saline solution is driven on into the patient. Finally the
blood flows steadily through the cannula, and the rate at which it is
flowing can be observed in the air-lock.

The presence of this air-lock facilitates, as has been seen, the
introduction of the cannula, into the vein, since there is no leakage
of blood to obscure the operation. In addition, the operator can
see at a glance whether the blood is flowing in properly, and can
regulate the rate of flow to a nicety by varying the pressure in the
flask by means of the bellows. If a very slow injection is required,
the blood can even be made to run drop by drop. If the patient is
suffering from acute anæmia, the blood can be pumped in rapidly, 750
cc. of blood being given in the course of twenty minutes. If, on the
other hand, the patient has a plethora of fluids, such as is seen in
some cases of secondary anæmia, the blood must be given very much
more slowly than this, since it is dangerous rapidly to increase the
blood volume. A half to three-quarters of an hour must be occupied in
giving 500 cc., and even then the patient may complain of a sensation
of tightness in the chest and of dyspnœa, due to embarrassment of
the right heart during the transfusion. This complaint, however, is
usually transient, and will disappear quickly if the injection be
stopped for a few minutes.

It has been said that the lower end of the delivery tube reaches
into the angle between the side and the bottom of the flask. When
therefore the flask is nearly empty, it should be tilted so that very
nearly the whole of the blood can be forced up the tube. When the
flask is quite empty, the blood in the barrel of the air-lock must
be carefully watched, and when its level has fallen to the bottom of
this, the clip must be applied to the tube above the cannula. By this
means no blood is wasted except the small quantity which remains in
the tube below the air-lock. As soon as the tube has been clipped the
cannula is withdrawn, the vein is ligatured above the opening into
its lumen, and the edges of the skin incision are sutured.

Transfusions carried out in this way can be performed with uniform
success. The technique is simple and straightforward at every stage,
and can be easily demonstrated and learnt. It is, in addition,
a perfectly clean process, and not a single drop of blood need
be spilt. Any method which involves the injection of blood under
pressure is open to the objection that it is possible to overlook
the fact that the flask has been emptied and to kill the patient
by injecting air into his veins. This can, however, only happen as
the result of great carelessness on the part of the operator. The
presence of the air-lock affords an additional safeguard, as it can
hardly escape the operator’s notice that blood has ceased to flow
from the nozzle of the delivery tube.

[Illustration: Fig. 13.--INJECTION OF THE BLOOD, SHOWING USE OF
AIR-LOCK]

The method may also be criticized on the ground that some damage is
caused to the corpuscles of the donor’s blood by the shaking which is
necessary to mix it with the citrate solution. This objection is,
in my opinion, theoretical rather than practical. If, however, it be
desired to avoid any such shaking, the apparatus designed by A. E.
Stansfeld and described by him in 1918 may be used. This ensures that
the citrate and the blood flow into the containing vessel together,
so that no further mixing is needed. The apparatus is more cumbrous,
more fragile, and less easy to clean and to sterilize than that
described above. In the hands of an expert it will give excellent
results, but its use requires some little practice, and it is
therefore not so well adapted for general use.

The whole of my own apparatus, as described above, may be obtained
from Messrs. Allen & Hanburys, Wigmore Street, London, W.1, who also
provide a convenient box for carrying it.


=Transfusion of Infants.=--The technique of transfusions performed
upon children over the age of about four years does not differ from
that used for adults, except that less blood is to be given. The
antecubital veins are much smaller and a finer cannula may have to
be used, but this is the only source of trouble. The transfusion of
infants and very young children may, however, be found to be much
more difficult. The operation will have to be done for conditions
such as melæna neonatorum, which was discussed on p. 48 of the
present work, or for post-operative collapse, such as may follow an
operation for congenital hypertrophic stenosis of the pylorus, for
intussusception, or for some of the more extreme cases of harelip
and cleft palate. In all such instances the transfusion will be a
matter of some urgency. Speed and certainty will depend on previous
knowledge of the best method to be employed.

In the case of melæna neonatorum treated by R. D. Laurie, which has
been already referred to, a needle was introduced into one of the
antecubital veins, and 20 cc. of citrated blood were injected with a
syringe. This method, however, is not to be recommended, on account
of its great difficulty.

The method used by Helmholtz and also by Howard depends on the
introduction of a syringe needle into the superior longitudinal
sinus through the anterior fontanelle. A needle two to three inches
long attached to a 20 cc. syringe is inserted near the upper angle
of the fontanelle at an angle of about 25° with the scalp. As the
needle pierces the wall of the sinus, a sensation of resistance is
experienced, similar to that given by the piercing of the dura mater
in doing a lumbar puncture. Blood should then be allowed to enter
the syringe in order to demonstrate that the point of the needle
really is lying in the sinus. Abnormalities have occasionally been
met with, in which the sinus was situated to one side of the middle
line or was very much smaller than usual. The danger of injecting
the blood in such a case into the brain or the subdural space need
not be emphasized. Difficulty may also be caused by restlessness on
the part of the child, and to overcome this Helmholtz has devised an
apparatus which grips and fixes the child’s head at a suitable angle.
All this, however, makes the process unnecessarily elaborate. As an
alternative, Vincent has exposed one of the internal jugular veins
into which he introduces a cannula. This again is a comparatively
difficult operation, which may leave a permanent scar in a
conspicuous place. Vincent had previously used the femoral vein, but
he found this difficult to approach, and the wound was apt to become
contaminated afterwards.

The method of choice is undoubtedly that used by Bruce Robertson,
who has performed a much larger number of transfusions upon infants
and children than any other worker in this field of surgery. He has
found that the internal saphenous vein near the ankle is a vessel
possessing a fairly wide lumen and thick walls even in infants, so
that a needle or cannula can be introduced into it with comparative
ease and rapidity. The vein must, of course, be freely exposed
through an incision, but its situation removes any objection there
might otherwise be to this operation. Robertson has usually employed
the syringe-cannula method described earlier in the present chapter,
but there is no objection to the use of an anticoagulant. The small
amount of blood to be given, 15 cc. per pound of body weight, makes
the use of the transfusion flask unnecessary. It is better to use a
20 cc. syringe, into which 2 cc. of a 10 per cent. solution of sodium
citrate is drawn as a preliminary. The needle in the donor’s vein and
the cannula in the infant’s saphena should each be provided with a
rubber connexion, which can be clipped, or pinched by an assistant,
when the syringe is not attached. The syringe containing the citrate
is filled with blood and injected into the infant as often as may be
necessary until the total amount decided upon has been given.

Robertson has used this method for complete replacement of the
circulating blood in treating streptococcal septicæmia following
erysipelas, and for shock in children due to burns. The infant’s
blood is removed through the anterior fontanelle, while a fresh
supply is injected into the saphenous vein. Complete replacement
has not, so far as I know, ever been performed upon an adult, but
the process is feasible, given a large enough assemblage of donors.
In this way some _vieillard_ might attempt the rejuvenation,
which at present, as we are told, has only been obtained from the
transplantation of “monkey glands” by Viennese professors.



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  2 vols., 4^o. Vol. i. p. 373; vol. ii. pp. 120, 605, 676.

  67. DAVID, V. C., & CURTIS, A. H.: “Experiments in the treatment
  of acute anæmia by blood transfusion and by intravenous saline
  infusion.” _Surg. Gyn. and Obstet._, 1912, xv. 476.

  68. DAVID, V. C., & CURTIS, A. H.: “Recent experiences with blood
  transfusion.” _Journ. Am. Med. Assoc._, 1914, lxii. 775.

  69. DAWSON, P. M.: “The changes in the heart rate and blood
  pressures resulting from severe hæmorrhage and subsequent infusion
  of sodium bicarbonate.” _Journ. Exp. Med._, 1905, vii. 1.

  70. DENYS, J.: “A letter concerning a new way of curing sundry
  diseases by transfusion of blood.” _Philosophical Trans._, 1667,
  ii. 489.

  71. DENYS, J.: “An extract of a letter touching a late cure of an
  inveterate phrensy by the transfusion of blood.” _Philosophical
  Trans._, 1667, ii. 617.

  72. DIEFFENBACH, J. F.: “Die Transfusion des Blutes und die
  Infusion der Arzneien in Blutgefässe.” Berlin, 1828.

  73. DIJK, H. VAN: “Malaria induced by convalescent’s serum.”
  _Nederl. Tijdschr. v. Geneesk._, 1920, ii. 1181.

  74. DORRANCE, G. M.: “Indications for blood transfusion.” _Am.
  Journ. Med. Sci._, 1917, cliv. 216.

  75. DORRANCE, G. M., & GINSBURG, N.: “Transfusion: history,
  development, present status and technique of operation.” _N.Y. Med.
  Journ._, 1908, lxxxvii. 941.

  76. DRINKER, C. R., & BRITTINGHAM, H. H.: “The cause of the
  reactions following transfusion of citrated blood.” _Arch. Int.
  Med._, 1919, xxiii. 133.

  77. DRUMMOND, H., & TAYLOR, E. S.: “The use of intravenous
  injections of gum acacia in surgical shock.” _Rep. of the Med. Res.
  Com._, iii., 1919, 135. “Observations on the blood pressure in gas
  gangrene infection.” _Ibid._, v. 1919, 199.

  78. DUKE, W. W.: “Variation in the platelet count.” _Journ. Am.
  Med. Assoc._, 1915, lxv. 1600.

  79. DUNGERN, E. VON, & HIRSCHFELD, L.: “Ueber Nachweis
  und Vererbung biochemischer strukturen.” _Zeitschr. f.
  Immunitätsfschng._, 1910, iv. 531; 1911, viii. 526.

  80. DUNGERN, E. VON, & HIRSCHFELD, L.: “Ueber Vererbung
  gruppenspezifischer strukturen des Blutes.” _Ibid._, 1910, vi. 284.

  81. DUNGERN, E. VON, & HIRSCHFELD, L.: “Ueber die Giftigkeit
  des Blutes nach der Injektion protoplasmatischen Substanzen und
  während der Schwangerschaft, und über passive Allergie gegenüber
  Hodensubstanzen.” _Ibid._, 1911, viii. 332.

  82. EBERLE, D.: “Transfusion and reinfusion of blood.” _Schweiz.
  med. Wchnschr._, 1920, l. 961.

  83. ELSBERG, C. A.: “A simple cannula for the direct transfusion of
  blood.” _Journ. Am. Med. Assoc._, 1909, lii. 887.

  84. ELY, A. H., & LINDEMAN, E.: “Acidosis complicating pregnancy.
  Report of a case cured by transfusion.” _Am. Journ. Obstet. and
  Dis. Wom. and Child._, July, 1916, lxxiv. 42.

  85. EMSHEIMER, H. W.: “Intramuscular injections of whole blood in
  the treatment of purpura hæmorrhagica.” _Journ. Am. Med. Assoc._,
  1916, lxvi. 20.

  86. EPSTEIN, A. A., & OTTENBERG, R.: “A method for agglutination
  tests.” _Arch. Int. Med._, 1909, iii. 286.

  87. ERLANGER, J., & GASSER, H. S.: “Hypertonic gum acacia and
  glucose in the treatment of secondary traumatic shock.” _Ann.
  Surg._, 1919, lxix. 389.

  88. FLEMING, A., & PORTEOUS, A. B.: “Blood transfusion by the
  citrate method.” _Lancet_, 1919, i. 973.

  89. FLÖRCKEN, H.: “Zur Frage der direkten Bluttransfusion durch
  Gefässnaht.” _Zentrbl. f. Chir. Leipzic_, 1911, xxxviii. 305.

  90. FOLLI, FRANCESCO: “Stadera medica, nella quale oltre la
  medicina infusoria, ed altre novita, si bilanciano le ragioni
  favore voli e le contrarie alla trasfusione del sangue.” Florence,
  1680.

  91. FORSIUS, R.: “Severe hæmophilic intestinal hæmorrhage treated
  with transfusion of blood.” _Finska Läkaresällskapets Handl._,
  1915, lvii. No. 3.

  92. FRANK, R. T., & BAEHR, G.: “A new method for the transfusion of
  blood. An experimental study.” _Journ. Am. Med. Assoc._, 1909, lii.
  1746.

  93. FRASER, J., & COWELL, E. M.: “A clinical study of the blood
  pressure in wound conditions.” _Report of the Med. Res. Com._, ii.
  (1), 1919, 49.

  94. FREILICH, E. B., and others: “Blood transfusion in treatment of
  pulmonary tuberculosis.” _Illin. Med. Journ._, 1921, xxxix. 32.

  95. FREUND, H. A.: “A method for the transfusion of fresh normal
  blood.” _Journ. Michigan Med. Soc._, 1913, xii. 459.

  96. FRY, H. J. B.: “The use of immunized blood donors in the
  treatment of pyogenic infections by whole blood transfusions.”
  _Brit. Med. Journ._, 1920, i. 290.

  97. FRYER, B. E.: “A few remarks on the transfusion of blood, with
  a modification of the apparatus of Aveling.” _Med. Rec._, 1874, ix.
  201.

  98. FULLERTON, A., DREYER, G., & BAZETT, H. C.: “Direct transfusion
  of blood, with a description of a simple method.” _Lancet_, 1917,
  i. 715.

  99. GARBAT, A. L.: “Intravenous injections of sodium citrate.”
  _Journ. Am. Med. Assoc._, 1916, lxvi. 1543.

  100. GESELLIUS, F.: “Die Transfusion des Blutes.” St. Petersburg,
  1873.

  101. GESELLIUS, F.: “Zur Thierblut-Transfusion beim Menschen.” St.
  Petersburg, 1874.

  102. GETTLER, A. O., & LINDEMAN, E.: “A new method of acidosis
  therapy. Blood transfusion from an alkalinized donor, with report
  of case.” _Journ. Am. Med. Assoc._, 1917, lxviii. 594.

  103. GIFFIN, H. Z.: “A report on the treatment of pernicious anæmia
  by transfusion and splenectomy.” _Journ. Am. Med. Assoc._, 1917,
  lxviii. 429.

  104. GRAHAM, J. M.: “Observations on the technique of blood
  transfusion.” _Edin. Med. Journ._, 1919, xxiii. 358.

  105. GRAHAM, J. M.: “Transfusion of blood in cases of hæmorrhage.”
  _Edinb. Med. Journ._, 1920, xxiv. 142.

  106. GRAHAM, J. M.: “Transfusion of blood in pernicious anæmia.”
  _Edinb. Med. Journ._, 1920, xxiv. 282.

  107. GRUTZ, O.: “Bluttransfusion bei Morbus maculosus Werlhofi.”
  _Berl. Klin. Wchnschr._, 1921, lviii. 53.

  108. GUIOU, N. M.: “Blood transfusion in a field ambulance.” _Brit.
  Med. Journ._, 1918, i. 695.

  109. GURYE, G. DE: “An account of more tryals of transfusion,
  accompanied with some considerations thereon, chiefly in reference
  to its cautious practice on Man; together with a farther
  vindication of this invention from usurpers.” _Philosophical
  Trans._, 1667, ii. 517.

  110. HAHN, M.: “Hæmophilia treated by transfusion.” _Med. Rec._,
  1910, lxxviii. 624.

  111. HALSTED, W. S.: “Refusion in the treatment of carbonic oxide
  poisoning.” _Ann. of Anat. and Surg._, 1884, Jan.

  112. HAPP, W. M.: “Appearance of iso-agglutinins in infants and
  children.” _Journ. Exp. Med._, 1920, xxxi. 313.

  113. HARDING, M. E.: “The toxæmic stage of diphtheria.” _Lancet_,
  1921, i. 737.

  114. HARRIS, D. T.: “The value of the vital-red method as a
  clinical means for the estimation of the volume of the blood.”
  _Brit. Journ. Exp. Path._, 1920, i. 142.

  115. HARTWELL, J. A.: “A simple method of blood transfusion with
  cannula.” _Journ. Am. Med. Ass._, 1909, lii. 297.

  116. HARTWELL, J. A.: “A consideration of the various methods of
  blood transfusion and its value.” N.Y. _State Journ. Med._, 1914,
  xiv. 535.

  117. HASSE, O.: “Report on twelve cases of the direct transfusion
  of lamb’s blood.” _Allgem. Wiener Medizin. Zeit._, Dec. 1873.
  (Abstracted in the _Lond. Med. Rec._, Dec. 31, 1873.)

  118. HÉDON, E.: “Note complémentaire sur la transfusion du sang
  citraté.” _Presse méd._, 1918, xxvi. 57.

  119. HEKTOEN, L.: “Iso-agglutination of human corpuscles.” _Journ.
  Infect. Dis._, 1907, iv. 297.

  120. HELMHOLZ, H. F.: “The longitudinal sinus as the place of
  preference in infancy for intravenous aspirations and injections,
  including transfusion.” _Am. Journ. Dis. of Children_, 1915, x. 194.

  121. HICKS, J. BRAXTON: “Cases of transfusion, with some remarks
  on a new method of performing the operation.” _Guy’s Hosp. Rep._,
  1869, 3rd s., xiv. 1.

  122. HIGGINSON, A.: “Report of seven cases of transfusion of blood,
  with a description of the instrument invented by the author.”
  _Liverpool Med. Chir. Journ._, 1857, i. 102.

  123. HINDSE-NIELSEN: “Nitro-benzol poisoning treated with blood
  transfusion.” _Ugeskift f. Laeger_, 1920, Sept. 9.

  124. HIRSCHFELD, L., & HIRSCHFELD, H.: “Serological differences
  between the blood of different races.” _Lancet_, 1919, ii. 675.

  125. HOFFMAN, M. H., & HABEIN, H. C.: “Transfusion of citrated
  blood.” _Journ. Am. Med. Assoc._, 1921, lxxvi. 358.

  126. HOOKER, R. S.: “The treatment of staphylococcus septicæmia by
  transfusion of immune blood.” _Ann. Surg._, 1917, lxvi. 513.

  127. HOWARD, W. S.: “A simple method of transfusion in hæmorrhage
  of the new-born, with report of a case.” _Journ. Am. Med. Assoc._,
  1915, lxv. 1365.

  128. HUCK, F. G.: “Changes in the blood immediately following
  transfusion.” _Johns Hopkins Hosp. Bull._, 1919, xxx. 63.

  129. HULL, A. J.: “Direct transfusion of blood.” _Brit. Med.
  Journ._, 1917, ii. 683.

  130. HUNT, E. L., & INGLEBY, H.: “A case of peptic ulcer with grave
  anæmia treated by intravenous injection of whole blood.” _Lancet_,
  1919, i. 975.

  131. HUNT, V. C.: “Reaction following blood transfusion by the
  sodium citrate method.” _Texas State Journ. Med._, 1918, xiv. 192.
  (Also in _Collected Papers of the Mayo Clinic_, x. 1918.)

  132. HUSTIN: “Principe d’une nouvelle méthode de transfusion
  muqueuse.” _Journ. méd. de Brux._, 1914, xii. 436.

  133. HUTCHISON, R.: “Three cases of melæna neonatorum successfully
  treated by the injection of whole blood.” _Brit. Med. Journ._,
  1917, ii. 617.

  134. HÜTER, C.: “Ein Fall von Kohlenoxydvergiftung; Heilung durch
  Transfusion.” _Berl. Klin. Wchnschr._, 1870, vii. 341.

  135. INGEBRIGTSEN, R.: “The influence of iso-agglutinins on the
  final results of homoplastic transplantation of arteries.” _Journ.
  Exp. Med._, 1912, xvi. 169.

  136. JANEWAY, H. H.: “An improved device for transfusion.” _Ann.
  Surg._, 1911, lxiii. 720.

  137. JANSKY, J.: “Hæmatologische Studien bei psykotiken.” _Klincky
  Sborink_, 1907, viii. 85.

  138. JANSKY, J.: “Recommendation by a committee that the Jansky
  classification of blood groups be used in preference to that of
  Moss on grounds, of priority.” _Journ. Am. Med. Assoc._, 1921,
  lxxvi. 130.

  139. KAHN, A.: “Continuous transfusion. The production of
  immunity.” _N.Y. Med. Rec._, 1916, lxxxix. 553.

  140. KARSNER, H. T.: “Laboratory problems of blood transfusion.”
  _Journ. Am. Med. Assoc._, 1921, lxxvi. 88.

  141. KEATOR, H. M.: “Transfusion in case of toxæmia of early
  pregnancy with unusual hæmorrhagic manifestations.” _Am. Journ.
  Obstet. and Dis. Wom. and Child_, 1912, lxv. 1003.

  142. KEITH, N. M.: “Blood volume changes in wound shock and primary
  hæmorrhage.” _Rep. of the Med. Res. Com._, ix., March, 1919.

  143. KEITH, N. M., ROWNTREE, L. G., & GERAGHTY, J. T.: “A method
  for the determination of plasma and blood volume.” _Arch. Int.
  Med._, 1915, xvi. 547.

  144. KEYNES, G. L.: “Blood transfusion: its theory and practice.”
  _Lancet_, 1920, i. 1216.

  145. KIMPTON, A. R., & BROWN, J. H.: “A new and simple method of
  transfusion.” _Journ. Am. Med. Assoc._, 1913, lxi. 117.

  146. KIMPTON, A. R.: “Further notes on transfusion by means of
  glass cylinders.” _Journ. Am. Med. Assoc._, 1913, lxi. 1628.

  147. KIMPTON, A. R.: “Transfusion. Experiences in over two hundred
  cases.” _Boston Med. and Surg. Journ._, 1918, clxxviii. 351.

  148. KIMPTON, A. R., & BROWN, J. H.: “Technique of transfusion
  by means of glass tubes.” _Bost. Med. and Surg. Journ._, 1915,
  clxxiii. 425.

  149. KING, E.: “An account of an easier and safer way of
  transfusing blood out of one animal into another, viz., by the
  veins, without opening an artery of either.” _Philosophical
  Trans._, 1667, ii. 449.

  150. KING, E.: “The method of transfusing into the veines of men.”
  _Philosophical Trans._, 1667, ii. 522.

  151. KING, E.: “An account of the experiment of transfusion,
  practised upon a man in London.” _Philosophical Trans._, 1667, ii.
  557.

  152. KING, H. H.: “Direct vein to vein transfusion.” _Brit. Med.
  Journ._, 1918, i. 498.

  153. KUSH, M.: “An automatic transfusion apparatus.” _Journ. Am.
  Med. Assoc._, 1915, lxv. 1180.

  154. LAMBERT, S. W.: “Melæna neonatorum, with report of a case
  cured by transfusion.” _N.Y. Med. Rec._, 1908, lxxiii. 885.

  155. LANDOIS, L.: “Die Transfusion des Blutes.” Berlin, 1866.
  Leipzig, 1875.

  156. LANDSTEINER, K.: “Ueber Agglutinationserscheinungen normalen
  menschlichen Blutes.” _Wien. Klin. Wchnschr._, 1901, xiv. 1132.

  157. LAPAGE, C. P.: “Two cases of melæna neonatorum treated by
  injection of fresh citrated blood.” _Proc. Roy. Soc. Med._, 1920,
  xiii. Sect. Child. Dis., 158-160.

  158. LAURIE, R. D.: “Melæna neonatorum treated by blood
  transfusion.” _Brit. Med. Journ._, 1921, i. 527.

  159. LEARMONTH, J. R.: “The inheritance of specific iso-agglutinins
  in human blood.” _Journ. Genetics_, 1920, x. 141.

  160. LEE, R. I.: “A simple and rapid method for the selection of
  suitable donors for transfusion by the determination of blood
  groups.” _Brit. Med. Journ._, 1917, ii. 684.

  161. LEISRINK, H.: “Ueber die Transfusion des Blutes.” _Samm. Klin.
  Vortr., No. 41._ Leipzig, 1872, 235.

  162. LESPINASSE, V. D.: “The treatment of hæmorrhagic disease of
  the new-born by direct transfusion of blood, with a clinical report
  of fourteen personal cases.” _Journ. Am. Med. Assoc._, 1914, lxii.
  1866.

  163. LESPINASSE, V. D.: “Technique of direct transfusion of blood,
  using iridio-platinum tubes.” _Chicago Med. Rec._, 1915, xxxvii.
  589.

  164. LESSER, L.: “Transfusion and autotransfusion.” _Samml. Klin.
  Vortr., No. 86_, Leipzig, 1875. _Inn. Med., No. 29_, p. 665.

  165. LEVIN, I.: “Plastic surgery of blood vessels and direct
  transfusion of blood.” _Ann. of Surg._, N.Y., 1913, May.

  166. LEWISOHN, R.: “A new and greatly simplified method of blood
  transfusion.” _N.Y. Med. Rec._, 1915, lxxxvii. 141.

  167. LEWISOHN, R.: “Blood transfusion by the citrate method.”
  _Surg. Gynec. and Obstet._, 1915, xxi. 37.

  168. LEWISOHN, R.: “The citrate method of blood transfusion in
  children.” _Am. Journ. Med. Sci._, 1915, cl. 886.

  169. LEWISOHN, R.: “The importance of the proper dosage of sodium
  citrate in blood transfusion.” _Ann. of Surg._, 1916, lxiv. 618.

  170. LEWISOHN, R.: “Modern methods of blood transfusion.” _Journ.
  Am. Med. Assoc._, 1917, lxviii. 826.

  171. LEYTON, O.: “Transfusion in diseases of the blood.” _Brit.
  Med. Journ._, 1919, i. 279.

  172. LIBAVIUS, A.: “Denfensio syntagmatis arcanorum chymicorum.”
  Frankfort, 1615, ch. iv., p. 8.

  173. LIBMAN, E., & OTTENBERG, R.: “A practical method for
  determining the amount of blood passing over during direct
  transfusion.” _Journ. Am. Med. Assoc._, 1914, lxii. 764.

  174. LIBMAN, E., & OTTENBERG, R.: “Recent observations on blood
  transfusion.” _Tr. Coll. Phys. Phila._, 1917, xxxix. 266.

  175. LICHTENSTEIN: “Eigenbluttransfusion bei Extrauteringravidität
  und Uterusruptur.” _Münch. Med. Wchnschr._, 1915, lxii. 1597.

  176. LINDEMAN, E.: “Simple syringe transfusion with special
  cannulas.” _Am. Journ. Dis. of Children_, 1913, vi. 28.

  177. LINDEMAN, E.: “Blood transfusion. Report of one hundred and
  thirty-five transfusions by the syringe-cannula system.” _Journ.
  Am. Med. Assoc._, 1914, lxii. 993.

  178. LINDEMAN, E.: “Reactions following blood transfusion by the
  syringe cannula system.” _Journ. Am. Med. Assoc._, 1916, lxvi. 624.

  179. LINDEMAN, E.: “The total blood volume in pernicious anæmia.”
  _Journ. Am. Med. Assoc._, 1918, lxx. 1292.

  180. LITTLE, G. F.: “Transfusion of antibacterial blood. Report of
  case.” _Journ. Am. Med. Assoc._, 1920, lxxiv. 734.

  181. LOSEE, J. R.: “Blood transfusion.” _Am. Journ. Med. Sci._,
  1919, clviii. 711.

  182. LOSEE, J. R.: “Blood transfusion in obstetrics.” _Med. Rec._,
  1920, xcvii. 265.

  183. LÖWENTHAL, W.: “Ein Beitrag zur Lehre von der Transfusion des
  Blutes.” _Berl. Klin. Wchnschr._, 1871, viii. 487.

  184. LOWER, R.: “The method observed in transfusing the blood out
  of one animal into another.” _Philosophical Trans._, 1666, i. 353.

  185. McCLURE, R. D.: “Pernicious anæmia treated by splenectomy, and
  systematic, often-repeated transfusion of blood. Transfusion in
  benzol poisoning.” _Journ. Am. Med. Assoc._, 1916, lxvii. 793.

  186. McCLURE, R. D., & DUNN, G. R.: “Transfusion of blood. History,
  methods, dangers, preliminary tests, present status. Report of one
  hundred and fifty transfusions.” _Johns Hopkins Hosp. Bull._, 1917,
  xxviii. 99.

  187. McGRATH, B. F.: “A simple instrument for [direct]
  transfusion.” _Journ. Am. Med. Assoc._, 1914, lxii. 40.

  188. McGRATH, B. F.: “Vascular suture in transfusion.” _Journ. Am.
  Med. Assoc._, 1914, lxii. 1326.

  189. McGRATH, B. F.: “A simple apparatus for transfusion by the
  aspiration-injection method.” _Surg. Gynec. and Obstet._, 1914,
  xviii. 376.

  190. MADGE, H. M.: “On transfusion of blood.” _Brit. Med. Journ._,
  1874, i. 42.

  191. MANN, F. C.: “Experimental surgical shock. The treatment of
  the condition of low blood pressure, which follows exposure of the
  abdominal viscera.” _Am. Journ. Physiol._, 1919, l. 86. (Also in
  _Collected Papers of the Mayo Clinic_, 1919, xi. 1225.)

  192. MARTIN: “Ueber eine mit günstigem Erfolge bei einer
  lebensgefährlichem Intrauterinblutung vollzogene Transfusion.”
  _Monatschr. f. Geburtsk. u. Frauenk._, 1861, xvii. 269.

  193. MARTIN: “Iso-agglutination beim Menschen.” _Centralblatt f.
  Bact._, 1905, xxxix. 704.

  194. MELENEY, H. E., STEARNS, W. W., FORTUINE, S. T., & FERRY, R.
  M.: “Post-transfusion reactions: a review of 280 transfusions.”
  _Am. Journ. Med. Sci._, 1917, cliv. 733.

  195. MILLER, G. I.: “Blood transfusion, indications and technique.”
  _Med. Rec._, 1915, lxxxviii. 425.

  196. MINOT, G. R.: “Methods for testing donors for transfusion of
  blood and consideration of factors influencing agglutination and
  hæmolysis.” _Boston Med. and Surg. Journ._, 1916, clxxiv. 667.

  197. MINOT, G. R., & LEE, R. I.: “The blood platelets in
  hæmophilia.” _Arch. Int. Med._, 1916, xviii. 474.

  198. MINOT, G. R., & LEE, R. I.: “Treatment of pernicious anæmia,
  especially by transfusion and splenectomy.” _Bost. Med. and Surg.
  Journ._, 1917, clxxvii. 761.

  199. MOREL, L.: “Transfusion of blood.” _Arch. gen. de Chir._,
  1914, viii. 1.

  200. MOSS, W. L.: “Studies on iso-agglutinins and iso-hemolysins.”
  _Johns Hopkins Hosp. Bull._, 1910, xxi. 63.

  201. MOSS, W. L.: “Paroxysmal hæmoglobinuria: blood studies in
  three cases.” _Johns Hopkins Hosp. Bull._, 1911, xxii. 238.

  202. MOSS, W. L.: “A simple method for the indirect transfusion of
  blood.” _Am. Journ. Med. Sci._, 1914, cxlvii. 698.

  203. MOSS, W. L.: “A simplified method for determining the
  iso-agglutinin group in the selection of donors for blood
  transfusion.” _Journ. Am. Med. Assoc._, 1917, lxviii. 1905.

  204. NIX, J. T.: “Blood transfusion simplified. Deductions from
  nineteen cases, eleven human and eight on dog.” _New Orleans Med.
  and Surg. Journ._, 1916, lxix. 435.

  205. OEHLECKER, F.: “Bluttransfusion von Vene zu Vene mit Messung
  der übertragenen Blutmenge.” _Zentralbl. f. Chir._, 1919, xlvi. 17.

  206. OEHLECKER, F.: “Direkte Bluttransfusion von Vene zu Vene bei
  perniziöse Anæmie.” _München. Med. Wchnschr._, 1919, lxvi. 895.

  207. ORÉ: “Études historiques et physiologiques sur la transfusion
  du sang.” Paris, 1868.

  208. OTTENBERG, R.: “Transfusion and arterial anastomosis.” _Ann.
  Surg._, 1908, xlvii. 486.

  209. OTTENBERG, R.: “Transfusion and the question of intravascular
  agglutination.” _Journ. of Exp. Med._, 1911, xiii. 425.

  210. OTTENBERG, R.: “The effect of sodium citrate on blood
  coagulation in hæmophilia.” _Proc. Soc. for Exp. Biol. and Med._,
  1916, xiii. 104.

  211. OTTENBERG, R.: “Medico-legal applications of human blood
  grouping.” _Journ. Am. Med. Assoc._, 1921, lxxvii. 682.

  212. OTTENBERG, R., & FRIEDMAN, S. S.: “The occurrence of grouped
  iso-agglutination in the lower animals.” _Journ. Exp. Med._, 1911,
  xiii. 531.

  213. OTTENBERG, R., & KALISKI, D. J.: “Accidents in transfusion.
  Their prevention by preliminary examination. Based on an experience
  of 128 transfusions.” _Journ. Am. Med. Assoc._, 1913, lxi. 2138.

  214. OTTENBERG, R., KALISKI, D. J., & FRIEDMAN, S. S.:
  “Experimental agglutinative and hemolytic transfusions.” _Amer.
  Journ. Med. Res._, 1913, xxviii. 141.

  215. OTTENBERG, R., & LIBMAN, E.: “Blood transfusion; indications;
  results; general management.” _Am. Journ. Med. Sci._, 1915, cl. 36.

  216. OTTENBERG, R., & THALIMER, W.: “Studies in experimental
  transfusion.” _Journ. Med. Res._, 1915-16, xxxiii. 213.

  217. PANUM, P. L.: “Experimentelle Untersuchungen über die
  Transfusion, Transplantation, oder Substitution des Blutes in
  theoretischer und praktischer beziehung.” _Virchow’s Arch. f. Path.
  Anat._, 1863, xxvii. 240, 433.

  218. PEMBERTON, J. DE J.: “Blood transfusion.” _Surg. Gynec. and
  Obstet._, 1919, xxviii. 262. (Also in _Collected Papers of the Mayo
  Clinic_, 1918, x. 508.)

  219. PEMBERTON, J. DE J.: “Practical considerations of the dangers
  associated with blood transfusions.” _Journ. Iowa State Med. Soc._,
  1920, x. 170. (Also in _Collected Papers of the Mayo Clinic_, 1919,
  xi. 635.)

  220. PERCY, N. M.: “A simplified method of blood transfusion, with
  report of six cases of pernicious anæmia treated by massive blood
  transfusions and splenectomy.” _Surg. Gynec. and Obstet._, 1915,
  xxi. 360.

  221. PETERSON, E. W.: “Purpura hæmorrhagica treated by blood
  transfusion.” _Post-Graduate_, N.Y., 1914, xxix. 499.

  222. PETERSON, E. W.: “Results from blood transfusion in the
  treatment of severe post-operative anæmia and the hæmorrhagic
  diseases.” _Journ. Am. Med. Assoc._, 1916, lxvi. 1291.

  223. PÉTREN, G.: “Coagulation time in icterus.” _Beitr. z. Klin.
  Chirurg._, 1920, cxx. 501.

  224. PONFICK: “Experimentelle Beiträge zur Lehre von der
  Transfusion.” _Virchow’s Arch. f. Path. Anat._, 1875, lxii. 273.

  225. POOL, E. H.: “Transfusion and splenectomy for von Jaksch’s
  anæmia in an infant.” _Ann. Surg._, March 1915. (In Transact. of
  N.Y. Surg. Soc.)

  226. POOL, E. H., & McCLURE, R. D.: “Transfusion by Carrel’s
  end-to-end suture method. With report of cases.” _Ann. Surg._,
  1910, lii. 433.

  227. POPE, L.: “Simplified transfusion.” _Journ. Am. Med. Assoc._,
  1913, lx. 1284.

  228. PRIMROSE, A.: “The value of the transfusion of blood in the
  treatment of the wounded in war.” _Ann. Surg._, 1918, lxviii. 118.

  229. PRIMROSE, A., & RYERSON, E. S.: “The direct transfusion of
  blood, its value in hæmorrhage and shock and in treatment of the
  wounded in the war.” _Brit. Med. Journ._, 1916, ii. 384.

  230. RAMIREZ, M. A.: “Horse asthma following blood transfusion.”
  _Journ. Am. Med. Assoc._, 1919, lxxiii. 984.

  231. RAMSAY, J.: “Transfusion of blood in nephritis.” _Brit. Med.
  Journ._, 1920, i. 766.

  232. RANSOM, S. H.: “The treatment of staphylococcus septicæmia by
  transfusion of immune blood.” _Ann. Surg._, 1917, lxvi. 513.

  233. RAULSTON, B. O., & WOODYATT, R. T.: “Blood transfusion in
  diabetes mellitus.” _Journ. Am. Med. Assoc._, 1914, lxii. 996.

  234. RICHARDSON, B. W.: “The cause of coagulation of the blood. The
  Astley Cooper prize essay for 1856, with additional observations
  and experiments.” London, 1858.

  235. RICHARDSON, E. H.: “Treatment of the emergency cases of
  ectopic pregnancy.” _Johns Hopkins Hosp. Bull._, 1916, xxvii. 262.

  236. ROBERTSON, L. B.: “The transfusion of whole blood.” _Brit.
  Med. Journ._, 1916, ii. 38.

  237. ROBERTSON, L. B.: “A contribution on blood transfusion in war
  surgery.” _Lancet_, 1918, i. 759.

  238. ROBERTSON, L. B.: “Blood transfusion in hæmorrhagic disease of
  the new-born.” _Brit. Med. Journ._, 1921, i.

  239. ROBERTSON, L. B.: “Blood transfusion in severe burns in
  infants and young children.” _Canad. Med. Assoc. Journ._, 1921, xi.
  744.

  240. ROBERTSON, L. B., & WATSON, C. G.: “Further observations on
  the results of blood transfusion in war surgery.” _Ann. Surg._,
  1918, lxvii. 1.

  241. ROBERTSON, O. H.: “The effects of experimental plethora on
  blood production.” _Journ. Exper. Med._, 1917, xxvi. 221.

  242. ROBERTSON, O. H.: “A method of citrated blood transfusion.”
  _Brit. Med. Journ._, 1918, i. 477.

  243. ROBERTSON, O. H.: “Transfusion with preserved red cells.”
  _Brit. Med. Journ._, 1918, i. 691.

  244. ROBERTSON, O. H.: “Memorandum on blood transfusion.” _Rep. of
  the Med. Res. Com._, iv. 1919, 143.

  245. ROBERTSON, O. H., & BOCK, A. V.: “Memorandum on blood volume
  after hæmorrhage.” _Rep. of the Med. Res. Com._, vi. 1919, 213.

  246. ROBERTSON, O. H., & BOCK, A. V.: “Blood volume in wounded
  soldiers.” _Journ. Exp. Med._, 1919, xxix. 139.

  247. ROSE, A.: “A case of melæna neonatorum successfully treated by
  the injection of blood serum.” _Brit. Med. Journ._, 1917, ii. 762.

  248. ROSE, C. W., & HUND, E. J.: “Treatment of pneumonic
  disturbances complicating influenza.” _Journ. Am. Med. Assoc._,
  1919, lxxii. 642.

  249. ROUS, P., & TURNER, J. R.: “The preservation of living
  red blood cells in vitro. I. Methods of preservation. II. The
  transfusion of kept cells.” _Journ. Exp. Med._, 1916, xxiii. 219.

  250. ROUS, P., & WILSON, G. W.: “Fluid substitutes for transfusion
  after hæmorrhage.” _Journ. Am. Med. Assoc._, lxx. 219-222.

  251. RUECK, G. A.: “Transfusion by the gravitation method.” _Med.
  Rec._, 1915, lxxxvii. 354.

  252. SALANT, W., & WISE, L. E.: “The action of sodium citrate and
  its decomposition in the body.” _Journ. Biolog. Chem._, 1917,
  xxviii. 27.

  253. SANFORD, A. H.: “Iso-agglutination groups: a diagram showing
  their interrelation.” _Journ. Am. Med. Assoc._, 1916, lxvii. 808.

  254. SANFORD, A. H.: “Selection of the donor for transfusion.”
  _Journ. Lancet_, 1917, xxxvii. 698.

  255. SANFORD, A. H.: “A modification of the Moss method of
  determining iso-hæmagglutination groups.” _Journ. Am. Med. Assoc._,
  1918, lxx. 1221. (Also in _Collected Papers of the Mayo Clinic_,
  1918, x. 504.)

  256. SATTERLEE, H. S., & HOOKER, R. S.: “Experiments to develop a
  more widely useful method of blood transfusion.” _Arch. Int. Med._,
  1914, xiii. 51.

  257. SATTERLEE, H. S., & HOOKER, R. S.: “The further development
  of an apparatus for the transfusion of blood.” _Surg. Gynec. and
  Obst._, 1914, xix. 235.

  258. SATTERLEE, H. S., & HOOKER, R. S.: “The use of hirudin in the
  transfusion of blood.” _Journ. Am. Med. Assoc._, 1914, lxii. 1781.

  259. SATTERLEE, H. S., & HOOKER, R. S.: “Transfusion of blood, with
  special reference to the use of anticoagulants.” _Journ. Am. Med.
  Assoc._, 1916, lxvi. 618.

  260. SAUERBRUCH: “Artery of donor introduced directly into
  recipient’s vein for transfusion of blood.” _Münch. Medizin.
  Wchnschr._, 1915, lxii. No. 45.

  261. SCHEEL, O., & BANG, O.: “Transfusion in a case of pernicious
  anæmia.” _Norsk Mag. f. Lægevidenskaben_, 1920, March.

  262. SCHLOSS, C. M., & COMMINSKEY, L. J. J.: “Spontaneous
  hæmorrhage in the new-born.” _Am. Journ. Dis. Child._, 1911, i. 276.

  263. SCHULTZ, W.: In Gravitz. “Klinische Pathologie des Blutes.”
  Leipsic, 1911, p. 381.

  264. SCHWEITZER: “Blood reinfusion in extra-uterine pregnancy.”
  _Münch. Med. Wchnschr._, 1921, lxviii. 699.

  265. SIMONS, I.: “Experiences with the sodium citrate method of
  indirect transfusion of blood.” _Journ. Am. Med. Assoc._, 1915,
  lxv. 1339.

  266. SHATTOCK, S. G.: “Chromocyte clumping in acute pneumonia and
  certain other diseases, and the significance of the buffy coat in
  the shed blood.” _Journ. Path. and Bact._, 1900, vi. 303.

  267. SMITH, T.: “Transfusion of blood in the case of a patient
  suffering from purpura.” _Lancet_, 1873, i. 837.

  268. SORESI, A. L.: “New instrument for direct transfusion of blood
  and temporary anastomosis between blood vessels.” _XVI. Internat.
  Med. Congr., Budapest_, 1909.

  269. SORESI, A. L.: “Clinical indications for direct transfusion of
  blood, with the author’s technique.” _Med. Rec._, 1912, lxxxi. 835.

  270. SPENCER, W. G.: “Transfusion of blood in civil practice.”
  _Med. Sci. Abstr. and Rev._, 1919, i. 309.

  271. STANLEY, L. L.: “Blood transfusion apparatus.” _Journ. Am.
  Med. Assoc._, 1920, lxxiv. 671.

  272. STANSFELD, A. E.: “The principles of the transfusion of
  blood.” _Lancet_, 1917, i. 488.

  273. STANSFELD, A. E.: “An apparatus for the transfusion of blood
  by the citrate method.” _Lancet_, 1918, i. 334.

  274. SYDENSTRICKER, V. P. W., MASON, V. R., & RIVERS, T. M.:
  “Transfusion of blood by the citrate method.” _Journ. Am. Med.
  Assoc._, 1917, lxviii. 1677.

  275. TARR, E. M.: “Intravenous injections in infancy. Advantage of
  the superior longitudinal sinus route.” _Arch. Pediatr._, 1919,
  xxxvi. 71.

  276. TELFER, S. V.: “Note on the preparation of sterile gum acacia
  solution for intravenous injection.” _Rep. of the Med. Res. Com._,
  i., 1919, 42.

  277. TERRIEN, E.: “Transfusion of blood in malignant measles.”
  _Bull. Soc. Méd. des Hôp._, 1919, xliii. 1134.

  278. THALIMER, W.: “Hæmoglobinuria after a second transfusion with
  the same donor.” _Journ. Am. Med. Assoc._, 1921, lxxvi. 1345.

  279. THOMAS, T. G.: “The intravenous injection of milk as a
  substitute for the transfusion of blood.” _N.Y. Med. Journ._, 1878,
  xxvii. 449.

  280. UNGER, L.: “Melæna neonatorum.” _Wien. Klin. Woch._, 1912,
  xxxix.

  281. UNGER, L. J.: “A new method of syringe transfusion.” _Journ.
  Am. Med. Assoc._, 1915, lxiv. 582.

  282. UNGER, L. J.: “Recent simplifications of the syringe method
  of transfusion.” _Journ. Am. Med. Assoc._, 1915, lxv. 1029.

  283. UNGER, L. J.: “Transfusion of unmodified blood, an analysis of
  one hundred and sixty-five cases.” _Journ. Am. Med. Assoc._, 1917,
  lxix. 2159.

  284. UNGER, L. J.: “Precautions necessary in the selection of a
  donor for blood transfusion.” _Journ. Am. Med. Assoc._, 1921,
  lxxvi. 9.

  285. VINCENT, B.: “Blood transfusion for hæmorrhagic diseases of
  the new-born. The use of the external jugular vein in infants.”
  _Boston Med. and Surg. Journ._, 1912, clxvi. 627.

  286. VINCENT, B.: “Blood transfusion with paraffin-coated needles
  and tubes.” _Surg. Gynec. and Obstet._, Nov. 1916.

  287. VINES, H. W. C.: “Anaphylaxis in the treatment of hæmophilia.”
  _Quart. Journ. Med._, 1920, xiii. 257.

  288. VINES, H. W. C.: “The coagulation of the blood. I. The rôle of
  calcium. II. The clotting complex.” _Journ. Phys._, 1921, lv. 86,
  287.

  289. VOGEL, K. M., & McCURDY, U. F.: “Blood transfusion and
  regeneration in pernicious anæmia.” _Arch. Internal. Med._, 1913,
  xii. 707.

  290. WAAG, A.: “Repeated small injections of blood in pernicious
  anæmia.” _Münch. Medizin. Wchnschr._, 1921, lxviii. 677.

  291. WALLICH, V., & LEVADITI, C.: “Recherches sur les réactions
  sanguines, à considérer à propos de la transfusion de sang.” _Bull.
  de l’Acad. de Méd._, 1914, lxxviii. No. 17.

  292. WARD, G.: “Transfusion of plasma.” _Brit. Med. Journ._, 1918,
  i. 301.

  293. WATSON, J. J.: “A method of fixation of vein to facilitate the
  introduction of a needle for intravenous injections.” _Journ. Am.
  Med. Assoc._, 1911, lvii. 383.

  294. WAUGH, W. G.: “An investigation of the end result in one
  hundred and twenty-four cases of blood transfusion.” _Brit. Med.
  Journ._, 1919, ii. 39.

  295. WEIL, P. E.: “Serum treatment of hæmophilia.” _Lancet_, 1920,
  ii. 300.

  296. WEIL, R. J.: “Sodium citrate in the transfusion of blood.”
  _Journ. Am. Med. Assoc._, 1915, lxiv. 425.

  297. WILLIAMSON, H.: “Blood transfusion before operation in severe
  secondary anæmias.” _Lancet_, 1920, i. 867.

  298. WOLTMANN, H.: “Transfusion by the citrate method in a
  sixty-hour-old baby with melæna neonatorum.” _Am. Journ. Med.
  Sci._, 1915, lxv. 2163.

  299. WREN, SIR C.: “An account of the rise and attempts of a
  way to conveigh liquors immediately into the mass of blood.”
  _Philosophical Trans._, 1665, i. 128.

  300. ZIEMSSEN, VON: “Ueber die subcutane Blutinjection und über
  eine einfache Methode der intravenösen Transfusion.” _Münch. Med.
  Wchnschr._, 1892, xix. 323.

  301. ZIMMERMANN, R.: “Blood transfusion in gynæcological cases.”
  _Münch. Med. Wchnschr._, 1920, lxvii. 898.

  302. ZIMMERMANN, R.: “Testing donor’s blood before transfusion.”
  _Zentralbl. f. Chir., Leipzig_, 1920, xliv. 1146.



INDEX


  Abdominal operations, shock in relation to, 27
    value of transfusion following, 32

  Abdominal veins, “bleeding into,” 27

  Accidents, loss of blood following, 20

  Acholuric jaundice, blood condition in, 93
    blood groups of patients with, 93
    transfusion in, 94

  Acidosis, in pregnancy, 63

  Agglutination, 84, 85
    abnormal, 56
    among animals, 79
    in infants and children, 84
    method of the test, 101
    phenomenon of, 71-73
    potential, of fœtal corpuscles, 85
    preceding hæmolysis, 70, 76

  Agglutinins, 71
    in the blood, discovery of, 15
    in maternal blood serum and milk, 86
    “major” and “minor,” 73
    “minor” in citrated blood, 123

  “Agglutinophilic” properties of blood corpuscles, 72, 85

  Agote, Prof., first transfusion of citrated blood by, 16

  Air hunger, 21

  Air-lock in transfusion apparatus, 125, 131, 133

  Alkaline solution in treatment of shock, 34

  Alkalinized blood, 63

  Amaurosis, 21

  Amputations, value of transfusion following, 32

  Anæmia, 19, 50
    acute, 19, 20
      amount of blood necessary in transfusion treatment, 25
      effect of transfusion on, 22
      following hæmorrhage, 20, 24
      signs and symptoms of, 20
      transfusion treatment of, 31
    aplastic, 50
    hæmophilia with, 48
    splenic, 50
    _see also_ Pernicious anæmia

  Anæsthesia, transfusion in conjunction with, 33

  Anæsthetics, shock accentuated by administration of, 31

  Anaphylactic shock, following transfusion, 77
    in pernicious anæmia, 57
    influence on coagulation time of blood, 45

  Anastomosis, Crile’s method, 109
    for direct transfusion, 108, 109

  Antecubital veins, injection of blood into, 134, 135

  Anti-agglutinins, 74

  Antibodies, in the blood, 58

  Anticoagulants, 16
    action of, 120, 122
    in hæmophilia, 47
    sodium citrate, 121
    transfusion with, 118

  Aplastic anæmia, 50

  Arm tourniquet, 126, 128

  Army, blood transfusion in, 17

  Arteries, in direct transfusion, 108, 109
    occlusion of, prevention of, 109
    selection of, for transfusion, 108

  Asthma, transmission of, 68

  Auto-hæmolysins, development of, 94

  Auto-hæmolysis of blood outside the body, 94
    phenomenon of, 94, 95


  Bacteria, blood inhibiting growth of, 58

  Bacterial infections, 58-63
    transfusion in relation to, 58, 60

  Benzol poisoning, transfusion treatment of, 65, 66

  Blood, administration of, apparatus for, 115, 126, 127, 130-133
      methods, 108, 112, 130-135
      time occupied in, 131, 132
    agglutinins and iso-agglutinins in, 15, 71, 72, 74
    amount in the body, how measured, 22, 23
    animals’, use of, 5, 6, 8, 9, 15
    anti-agglutinins in, 74
    antibodies in, 58
    auto-hæmolysis of, 94
    bactericidal power of, 58
    calcium content of, 120
    citrated, _see_ Citrated blood
    clotting of, _see_ Coagulation
    coagulation of, _see_ Coagulation
    defibrinated, early use of, 11, 12
    examination of, for transfusion, 56, 57, 95
    hydrogen-ion concentration of, 28
    immunized, in pyogenic infections, 58
    inhibiting growth of bacteria, 58
    loss of, _see_ Hæmorrhage
    maternal, agglutinins in, 86
    of donors, _see_ Blood donors
    of patients, reinfusion with, 42, 43
      testing of, 56
    rapid administration, danger of, 78
    substitutes for, 35, 36
    testing of, for transfusion, 68, 83, 92, 95
    total quantity in the body, 22
    transfused, corpuscles in, 37
      relative value of corpuscles and plasma in, 36, 37
    withdrawal of, methods and technique, 108, 112, 116, 126-128

  Blood clot, mechanism of formation of, 119
    rapid hæmorrhage causing, 24
    _see also_ Coagulation

  Blood corpuscles, “agglutinophilic” properties of, 72, 85
    and plasma, relative value of, 36, 37
    clumping together of, 70
    condition during shock, 39
    conditions due to alterations in, 50
    destruction of, in the toxæmias, 64
    effect of transfusion on, 52
    fœtal, potential agglutination of, 85
    in transfused blood, 36, 37
    function of, 37
    quantity and concentration during shock, 28
    transfusion of, 64

  Blood count, during shock, 39
    following hæmorrhage, 39
    following transfusion, 40
    in pernicious anæmia, 51, 53-56

  Blood diseases, 50-58

  Blood donor, 69
    blood of, 56, 57
      agglutinating power of serum of, 72-74
      testing of, 68
      transmission of disease by, 67, 68
    characteristics of, 100
    choice of, 68, 96-107
    effect of blood loss on, 99
    for new-born infants, 49
    for pernicious anæmia, 56, 57
    injury to, during transfusion, 111, 124
    members of patient’s family as, 85, 90, 92, 95
    “professional,” 69, 98
    testing of, 83, 92, 95-97
      for blood groups, 101
    treatment of, 60, 99, 100
    “universal,” 72, 73
    vaccine treatment of, prior to withdrawal of blood, 60
    withdrawal of blood from, 108, 109, 124
      by anastomosis, 108, 109
      by Kimpton-Brown tube, 116, 117
      by needle, 126-128
      by syringe, 112, 113

  Blood groups, 67, 69, 70, 101
    among animals, 79
    and disease, relation between, 81, 93
    classification of, 70, 71
    compatibility of, 72, 75, 80
      in families, 84, 90, 92
      testing of, 102
    earliest classification of, 15
    family incidence of, 84, 90, 92
    incidence among our own population, 83
    incompatibility of, 80, 92
      earliest reference to, 6
      in animals, 80
      in families, 84, 90, 92
      symptoms of, 75-77
      testing for, 101, 102
    inheritance of, 86, 87, 90, 91
      medico-legal considerations, 92
    maternal, compared with those of infants, 86, 92
    over-lapping of, 72, 96
    pathology of, 79
    phenomena of, 69-75
    physiology of, 79
    popular beliefs concerning, 84
    racial incidence of, 81, 82
    reactions between the serum and corpuscles of, 70, 71, 72, 73
    testing for, in blood donors, 97, 101
    transfusion in relation to, 95
    “unit characters” in, 86, 87, 88

  Blood measurements, 22, 23

  Blood plasma, in transfused blood, 36, 37

  Blood pressure, 21
    as an indication for transfusion, 40
    danger points in, 21
    following loss of blood, 21
    low, essential feature of shock, 27
      transfusion treatment of, 32

  Blood reactions, 70, 71, 72, 80, 101
    clinical picture of, 75
    disease in relation to, 93
    family incidence of, 84, 90, 92, 95
    following transfusion, 95, 96, 122, 123
    in infants, 84, 90, 92
    incompatibility of, transfusion in relation to, 96
    intensity of, variations in, 73
    recognition of symptoms of, 75-77
    variation in degree of, 76

  Blood recipients, “universal,” 72, 95

  “Blood relations,” transfusion in relation to, 84, 92, 95

  Blood serum, agglutination test of, 101
    preservation of, 101, 102
    stock, 101
      collection of, 102

  Blood volume, changes in, in hæmorrhage and shock, 24, 25, 27
    diminution in shock, 27, 32
      estimation of, 22
      imperfect oxygenation due to, 36
    life dependent on, 24, 25

  Blundell, James, his “impellor,” 10, 11
    transfusion by (in 1818), 10, 11

  Body, total quantity of blood in the, 22

  Breathing, difficult, during transfusion, 78

  Burns, transfusion for shock due to, 136


  Calcium, action of, 120
    in the blood, forms in which present, 120
    precipitation of, 119

  Cancer, transfusion for, 9, 18

  Cannula, for direct transfusion, 110
    for indirect transfusion, 130

  Capillary circulation, condition during shock, 39
    stagnation of, following hæmorrhage and shock, 27, 29

  Carbon monoxide poisoning, 64
    condition of the blood in, 64
    transfusion treatment of, 64, 65

  Children, transfusion of, technique, 134
    _see also_ Infants

  Chloroform, shock accentuated by administration of, 31

  Chlorosis, 50

  Circulation, blood volume necessary to maintain balance of, 24, 25
    capillary and venous, comparison during shock, 39
    condition during shock and hæmorrhage, 27, 28, 29, 39
    stagnation of, 28
    _see also_ Blood

  Citrate reactions, 122, 123

  Citrated blood, 16, 121, 124
    administration of, methods, 129-134
    keeping and care of, 128, 129
    reaction following use of, 122, 123
    transfusion of, 121, 124
      first recorded case of, 16
      in pernicious anæmia, 51, 56
    _see also_ Sodium citrate

  Clotting, _see_ Coagulation

  Coagulation, deficient, following hæmorrhage, 41
    difficulties connected with, in early experiments, 11, 12
    effect of transfusion on, 42

  Coagulation, mechanism of production of, 119
    outside the body, 118, 119
    prevention of, 114, 120

  Clotting, prevention of, by sodium citrate, 119, 120
    prevention of, during transfusion, 109, 110, 112
    transfusion simplified by prevention of, 119

  Coagulation time, anaphylactic shock influencing, 45
    effect of transfusion on, 46, 47
    hæmorrhage in relation to, 44, 45
    in jaundice, 44
    prolongation of, 44

  Coal-gas poisoning, transfusion treatment of, 64

  Coga, Arthur, 8

  Cold, predisposing to shock, 29, 30

  Cox, Thomas, transfusion experiments by, 3

  Crile, improvement in technique of transfusion by, 15
    method of direct transfusion, 109

  Curtis and David, improvements in technique of transfusion by, 16


  Daniel, of Leipsic, 3

  Darwin, Erasmus, 9

  Death, loss of blood causing, 24

  Denys, John, first human transfusion performed by, 3, 5, 6

  Diabetes mellitus, transfusion in, 66

  Diphtheria, 60
    acute toxæmia in, 60
    experimental transfusion in, 60, 61

  Direct transfusion, apparatus for, 109, 110
    methods, 108, 109, 110
    objections to, 110, 111
    technique of, 108-111

  Disease, relation between blood groups and, 81, 93
    transmission by blood transfusion, 68

  Drysdale, Dr. J. H., 52

  Duodenal ulcer, severe hæmorrhage from, transfusion treatment, 41


  Eclampsia, “fœtal threat” in relation to, 85
    transfusion treatment, 62

  Ectopic gestation, rupture of, transfusion following, 42

  Elsberg and Bernheim’s method of direct transfusion, 109

  Emboli, multiple, 77

  Endocarditis, transfusion for, 60

  Ether, shock accentuated by administration of, 31


  Fever, transfusion for, 9

  Fluids, administration of, during shock, 34

  “Fœtal threat,” 85

  Folli, Francesco, supposed blood transfusion by (1654), 2

  Fontanelle, use of, 135, 136

  Forced fluids, 34

  Fullerton’s method of direct transfusion, 110


  Gametes, segregation of, 88

  Gastric ulcer, severe hæmorrhage from, transfusion treatment, 41

  Grafts, tissue, 80

  Gum transfusion, 35, 36, 37
    and blood transfusion, relative value of, 35, 37
    objections to, 36

  Gurye, Gaspar de, 6


  Hæmatemesis, treatment of, 41

  Hæmoglobin percentage, during shock and hæmorrhage, 39

  Hæmoglobinuria, 6, 7, 70
    as symptom of blood reaction, 76
    following blood transfusion, 76
    paroxysmal, blood condition in, 94

  Hæmolysed blood, toxicity of, 77

  Hæmolysins, 71

  Hæmolysis, 94, 95
    agglutination preceding, 70, 76
    early reference to, 6

  Hæmophilia, anæmia with, 48
    anticoagulants in, 47
    blood condition in, 45
    sodium citrate administration in, 47, 48
    transfusion treatment of, 45-48

  Hæmophilics, coagulation time of blood of, 46, 47
    transfusion beneficial to, 46

  Hæmorrhage, 20
    acute anæmia following, 20, 24
    blood counts following, 39
    blood-volume changes in, 24, 25, 27

  Hæmorrhage, coagulation time in relation to, 44, 45
    condition of blood following, 24, 27, 28, 39
    danger of, 20, 23
    effects of, how combated, 33
    following gastric or duodenal ulcer, transfusion treatment, 41
    general treatment of, 31, 33
    gum treatment of, 35, 36
    in new-born infants, transfusion treatment, 49
    intraperitoneal, 42
    limits of, 24
    post-partum, transfusion treatment, 42
    rapid, 23, 24
    reflex compensation for, 99
    reinfusion treatment of, 42
    saline treatment of, 33
    secondary, 40, 41
      indications for transfusion in, 41
    shock always associated with, 20, 26
    shock and, clinical difference between, 38
    signs and symptoms of, 38
    transfusion treatment of, 20, 25, 31
      effects of, how judged, 40
      indications for, 40
    traumatic, 40

  Hæmorrhagic diseases, 44-50

  Hæmostasis, blood transfusion producing, 42, 44, 45, 48

  Harvey, William, his theory of the circulation, 2

  Heart, dilatation of, 78
    effect of loss of blood on, 23

  Helmholtz, method of transfusion of infants, 135

  Heredity, blood groups in relation to, 86, 87, 90, 91
    Mendelian theory of, 86, 90

  Higginson’s transfusion instrument, 13, 14

  Hirudin, use of, 16

  Histamine, 30
    production of, 30
    production of shock by, 30

  Horse asthma, transmission of, 68

  Howard’s method of transfusion of infants, 135

  Hydrogen-ion concentration in the blood, 28, 31
    shock in relation to, 28, 32

  Hydrophobia, transfusion for, 9


  Immunized blood, transfusion by, in pyogenic infections, 58

  Incompatibility, symptoms of, 6, 75

  Indirect transfusion, 111

  Infants, blood groups in, 84, 92
    compared with those of mothers, 86, 92
    blood reactions in, 84, 90, 92
    transfusion of, 48
      conditions necessitating, 49, 134
      dosage, 136
      technique, 134-136
      with maternal blood, 85, 92
    withdrawal of blood from, 136

  Influenzal pneumonia, transfusion for, 61

  Innocent VIII, 2

  Internal saphenous vein, injection of blood into, in infants, 135

  Iso-agglutinins, 72, 79
    distribution among animals, 79, 80

  Iso-hæmolysins, 72, 79
    in animals, artificial reproduction of, 96

  Isotonic saline solution in treatment of shock, 34


  Jaundice, 44
    acholuric, transfusion in, 94
    blood groups in patients with, 93
    hæmorrhage following operation in cases of, 44
    transfusion in cases of, 44

  Joekes, Dr., 52, 57

  Jugular vein, injection of blood into, 135


  Keith, on blood volume changes, 24, 27
    on shock and hæmorrhage, 32

  Kimpton and Brown, improvements in technique of transfusion by, 16

  Kimpton-Brown tube, whole blood transfusion with, technique, 114

  King, Edmund, transfusion experiments by, 3, 4, 8


  Lamb’s blood, early transfusions with, 5, 9, 15

  Legitimacy, inheritance of blood groups in relation to, 92

  Leukæmia, 50
    blood groups in patients suffering from, 81

  Lewisohn’s sodium citrate experiments, 16, 120, 122, 123

  Longitudinal sinus, use of, 135

  Lower, Richard, transfusion experiments by, 3, 8


  Malaria, transmission by transfusion, 67, 68

  Malignant disease, blood groups in patients suffering from, 81, 93

  “Maternal threat,” 85, 92

  Measles, blood injections in, 62

  Median basilic vein, accessible for direct transfusion, 108
    incision of, 130
    puncture of, 126-128

  Melæna neonatorum, transfusion for, technique, 134, 135
    value of transfusion in, 48

  Mendelian theory, 86, 90
    of blood groups, 86, 87, 88, 90

  Milk, injection of, 15
    maternal, agglutinins in, 86

  Muscle, damaged, production of histamine from, 30


  Needle, for transfusion, 126
    case of, 126
    improved form of, 113

  Nephritis, transfusion treatment of, 63

  New-born infants, blood donors for, 49
    blood reactions of, 84, 90, 92
    hæmorrhagic disease of, 48, 49
    transfusion of, 48
      technique, 134-136
      with maternal blood, 84, 85, 92

  Nitrobenzol poisoning, transfusion treatment of, 65


  Obstetrics, transfusion in, 42

  Operations, shock following, 31
    value of transfusion following, 32

  Osmotic pressure, 36
    significance of, 36

  Oxygenation, imperfect, blood loss causing, 36
    solutions increasing, 37

  Oxyhæmoglobin, conversion into carboxyhæmoglobin in carbon monoxide
        poisoning, 64

  Pain, predisposing to shock, 29

  Paraffin wax, coating of glass tube with, 114, 116
    in prevention of clotting, 110, 114

  Paroxysmal hæmoglobinuria, blood conditions in, 94

  Pedigree of blood groups, 90

  Pellagra, transfusion in cases of, 66

  Pepys, Samuel, 7, 8, 9

  Pernicious anæmia, 50
    blood condition in, 93
    blood count in, 51, 53-56
    blood groups in patients with, 93
    subcutaneous blood injections in, 58
    transfusion treatment of, 50-58, 95
      complications of, 57
      cases illustrating, 53-55
      choice of blood donor, 56, 57
      dosage, 52
      reactions following, 57

  Perspiration, blood loss due to, 28

  Placenta prævia, transfusion following, 42

  Pneumonia, transfusion in cases of, 61

  Poisoning, transfusion treatment of, 64, 65

  Post-operative shock, 31

  Post-partum hæmorrhage, 42

  Pregnancy, toxæmias, of “fœtal threat” in relation to, 85
    transfusion treatment of, 62

  “Professional” blood donor, 69, 98

  Purpura, transfusion in cases of, 49, 50

  Pyæmia, transfusion in cases of, 59
    transfusion in, 58


  Radial artery, accessible for direct transfusion, 109
    exposure of, 111
    objections to use of, 111

  Reactions, 75, 76
    following transfusions, 57, 122, 123
    _see also_ Blood reactions

  Reinfusion with patient’s own blood, 42, 43

  Rejuvenation, 136

  Replacement of blood, complete, 136

  Respiratory system, effect of loss of blood on, 23
    exhaustion of, 21

  Robertson, Bruce, transfusion of infants and children by, 135, 136

  Robertson, Oswald, transfusion with citrated blood by, 121, 124

  “Robertson’s bottle,” 124, 125


  Saline infusion, treatment of shock by, 33

  Saphenous vein, internal use of, 130, 135

  Sauerbruch’s method of direct transfusion, 108

  Segregation of the gametes, 88

  Septicæmia, transfusion for, 59, 136

  Serum, _see_ Blood serum

  Shock, 20
    abdominal operations in relation to, 27
    alkaline administration during, 34
    anaphylactic, _see_ Anaphylactic shock
    avoidance of, following hæmorrhage, 29
    blood count during, 39
    blood volume changes in, 24, 25, 27, 32
    capillary system during, 27, 28, 29
    causal theories of, 26, 27
    conditions of the blood during, 24, 27, 28, 39
    effects of, how combated, 33
    experimental production of, 30
    fluid administration during, 34
    gum treatment of, 35, 36
    hæmorrhage always associated with, 26
    hæmorrhage and, differential diagnosis, 38, 39
    hydrogen-ion concentration in relation to, 28, 32
    low blood pressure the essential feature of, 27
    mechanism of production of, 30
    post-operative, 31
    primary, 29
    reinfusion treatment, 42
    saline treatment of, 33
    secondary, 29
      conditions predisposing to, 29
    signs and symptoms of, 26, 29, 38
    theories regarding, 26
    toxic theory of, 30
    transfusion treatment of, 20, 26, 31
      indications for, 40

  Skin eruption, as symptoms of blood reaction, 76, 77

  Sodium bicarbonate, in treatment of shock, 34

  Sodium citrate, absorption and elimination of, 120
    action of, 122
    as an anticoagulant, 16, 121
    coagulation time of the blood reduced by, 47
    dosage, 121, 122
    elimination of, 120
    form in which used, 123
    in hæmophilia, 47
    in prevention of clotting, 119, 120
    reactions following use of, 122, 123
    tolerance to, 122
    toxicity of, 77

  Sodium phosphate, use of, 16

  Solutions, for transfusion, essential constituents of, 36, 37
    viscosity and osmotic pressure of, 36

  Spinal anæsthesia, transfusion in conjunction with, 33

  Splenic anæmia, 50

  Stansfeld’s apparatus, 134

  Staphylococcal septicæmia, blood transfusion in, 59, 60

  Sterility and blood groups, 80

  Streptococcal septicæmia, blood transfusion in, 136

  Syphilis, transmission by blood transfusion, 68

  Syringe, cleansing of, 114
    Higginson’s, 13, 14
    whole blood transfusion with, technique, 112-114


  Tissue transplantation, success of, dependent upon compatibility of
        blood groups, 80

  Tissues, damage to, producing toxic substances, 30

  Tourniquet, Canti’s, 126, 128

  Toxæmia, 58-66
    acute, in bacterial diseases, 60
    blood transfusion in, 31, 58, 60, 61
    of pregnancy, transfusion treatment of, 62
    traumatic, 30-32
      production of, 30

  Toxic theory of shock, 30

  Transfusion, apparatus for, 115, 126, 127, 130-133
      in early experiments, 10, 13
      recent improvements in, 15
    continuous, 60
    direct method, technique, 108-111
    early objections to, 9
    history of, 1
    ideal method of, 124, 132
    indirect method, technique, 111-112
    of infants, 134
      technique, 134
    recent advances in knowledge and technique of, 15-17
    repeated, 57
    Robertson’s citrate method, 121, 124
      apparatus for, 124, 134
    whole blood, with syringes, technique, 112
    with anticoagulants, technique, 118-134
    with Kimpton-Brown tube, 114

  Traumatic toxæmia, 30-32

  Tuberculosis, transfusion in, 62

  Twins, blood groups in, 92

  Typhoid, transfusion in, 62


  “Universal donors,” 72, 73

  “Universal recipients,” 72

  Urine, hæmoglobin in, 39, 70, 76
    suppression of, 76, 77

  Urticaria, following transfusion, 77

  Uterus, rupture of, 42


  Vaccine, injection of, into blood donors, 59, 60

  Vaso-motor failure, in shock, 26

  Vein, for direct transfusion, 108, 109
    injection of blood into, 134, 135
    insertion of cannula in, 131
    occlusion of, prevention of, 109
    puncture of, 113
      technique, 126-128
    prevention of injury to, 113, 124

  Venesection, preceding transfusion, 60
    in carbon monoxide poisoning, 65

  Venospasm, 27

  Venous circulation, condition during shock, 39

  Viscosity, 36
    significance of, 36

  Vital red, use of, 23


  War, transfusion in, 17

  Water, during severe shock, 34

  Whole blood transfusion, apparatus for, 114
    objections to, 118
    prevention of clotting, 114, 118
    with Kimpton-Brown tube, technique, 114-118
    with syringes, 112-114

  Willis, Thomas, 3

  “Wound shock,” 29

  Wren, Sir Christopher, vein injections by, 2, 3


FOOTNOTES:

[1] The first reference to this that I can find is in “Moines et
Papes,” by Emile Gebhardt, _La Chronique Médicale_, November 1912.

[2] _Life and Times of Rodrigo Borgia_, A. H. Mathew, D.D., 1912,
p. 66.

[3] This refers to the experiment of Denys, mentioned above.

[4] Birch’s _History of the Royal Society_, 1756, ii. p. 216.

[5] The notation used here is that initiated by Moss in 1910. This
does not agree with the notation introduced three years previously by
Jansky, the Groups I and II of Moss corresponding to the Groups IV
and III of Jansky and _vice versa_. The difference has given rise to
confusion and some disasters, and it has been recently recommended
by an American Medical Committee that the notation of Jansky be
universally adopted on grounds of priority. This decision is no
doubt fully justified in American practice, but in this country the
notation of Moss has been so generally used that I have not attempted
to reverse it. The possible dangers that may arise should, however,
be realized.

[6] _Mendelism_, R. C. Punnett, 5th ed., Macmillan, 1919.

[7] J. A. Kolmer, _Infection, Immunity, and Specific Therapy_, ed.
2, Saunders Co., 1917, p. 287: “With the increasing number of blood
transfusions the phenomena of iso-agglutination and iso-hæmolysis
are of considerable practical importance, especially if the patient
is suffering from cancer, when the serum is likely to be actively
hæmolytic for the donor’s corpuscles.” No authority is given.

[8] This embodies the same principle as the “dropper” designed by R.
D. Laurie.

[9] A very convenient form of tourniquet is that designed by R. G.
Canti. It is sold by Messrs. Maw & Sons, and by Messrs. Allen &
Hanburys.



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