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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.