Transfusion Medicine: A History

Januarius/Gennaro
Bishop of Benventum, beheaded in 305 for refusing to worship pagan gods.
2 sealed phials of his blood and his head put in the Cathedral at Naples in
1497 and these have resulted in miraculous deliverance from the volcano of
Vesuvius, 8 miles distant (e.g. 1631, 1707). On 19 Sept, 20 Dec and in May,
these are examined. The congealed blood may liquify and boil and
re-solidify. Liquifaction of the blood seldom fails to occur on his feast
days and may occur as much as 18 times during the year when it is exposed
and placed near his head.
3
If liquified on the feast days, Neapolitans will have good luck.

Albertus magnus

Anaesthesiologists
Missionary to the Hurons. Tortured and killed
by Iroquois, enemies of the Hurons, for making
the sign of the cross of a child's head. First
North American martyr. His death by
tomahawk in the head led to his patronage of
people who work with or receive anaesthesia.
.

Medical technologists
Son of a military nobleman. Dominican Priest.
Taught theology at Cologne and Paris. Teacher
of St Thomas Aquinas. Introduced Greek and
Arabic science and philosophy to medieval
Europe. Known for his wide interest in what
became known later as the natural sciences botany, biology, etc. Wrote and illustrated
guides to his observations, and was considered
on a par with Aristotle as an authority on these
matters.
4

Alexius
Camillus of
Lellis

Agatha

Hospital administrators
Basil the Great

Frances Xavier Cabrini

Catherine of
Alexandria

Margaret of
Antioch

Catherine of
Sienna

5 the
Raphael
Archangel

Ovid: Metamorphoses, seventh book (43 BCE)

Jason pleaded that Medea restore the youth of his father, King
Aeson.
Medea took her unsheaved knife and cut the old mans throat,
letting all of his old blood out of him. She filled his veins with a
rich elixir, which he received through his lips and wound. His
beard and hair, no longer white with age, turned quickly to
their natural vigour, dark and lustrous; and his wasted form
renewed, appeared in all the vigour of bright youth

Ovid's influence on Western art and literature cannot be exaggerated. The Metamorphoses is our best classical
source of 250 myths. The poem is the most comprehensive, creative mythological work that has come down to
us from antiquity. Based on its influence, "European literature and art would be poorer for the loss of the
Metamorphoses than for the loss of Homer" (Hadas). Ovid was a major inspiration for Dante, Chaucer,
Shakespeare, Milton. If Virgil is Rome's greatest poet, Ovid is the most popular.

Medeas Rx:
In a bronze cauldron:
root herbs, seeds and flowers, strong juices and pebbles from
the farthest shores of oceans east and west, hoarfrost taken at
full of moon, a hoot owls wings and flesh, a werewolfs
entrails, the fillet of a snake, the liver of a stag, and the eggs
and head of a crow which had been alive for nine centuries

Blood in the Bible

Leviticus 17:11

the life/soul of the flesh is in the blood
no soul you shall eat blood

Matthew 26:28
take drinkthis is my blood, which is shed for
you for the remission of sins

Blood in History
China, 1000 BCE: The soul was contained in the blood.
Egyptian kings bathed in blood for their health.
Taurobolium, the practice of bathing in blood as it cascaded
from a sacrificial bull, was practiced by the Romans.
Pliny and Celsus describe Romans drinking the blood of
fallen gladiators to gain strength and vitality and to cure epilepsy.
Galen advised drinking of blood of a weasel or a dog for rabies.
Ancient Norwegians drank blood of seals and whales as a remedy
for epilepsy and scurvy.
9

[Brown HM: The beginnings of intravenous medication. Ann Med Hist 1:177, 1917]

Phlebotomy, or bloodletting, is the longest-running tradition in medicine, originating

in the ancient civilizations of Egypt and Greece, persisted through the Medieval,
Renaissance, and Enlightenment periods, flourished in Arabic and Indian medicine,
and lasted through the second Industrial Revolution. The practice continued for
2,500 years until it was replaced by the techniques of modern medicine.
Doctors bled patients for every ailment imaginable. They bled for pneumonia and
fevers, back pain and rheumatism, headaches and melancholia; even to treat bone
fractures and other wounds. Yet there never was any evidence that phlebotomy did
any good.
Bloodletting was based on an ancient system of medicine in which blood and other
bodily fluid were considered to be "humors" whose proper balance maintained
health. Sick patients were thought to have an imbalance of their humors, which
bloodletting was thought to restore.
10

Bleeding was as trusted and popular in ancient days as aspirin is

today. The Talmudic authors laid out complex laws for bloodletting.
Medieval monks bled each other several times a year for general
maintenance of health. Doctors devised elaborate charts indicating
the most favorable astrological conditions for bleeding.
It wasn't until well into the 19th century that people began to
question the value of bloodletting. Scientists such as Louis Pasteur,
Joseph Lister, and Robert Koch showed that germs, not humors,
were responsible for disease. Furthermore, medical statisticians
tracking case histories began to collect evidence that bloodletting
was not effective.
Eventually the practice died, although it continued in some parts of
rural America into the 1920s.

11

Bleeders used an impressive array of hardware. The mainstay was the

lancet, a small, sharp, two-edged knife. Wielding the lancet took quite a
bit of skill; a false cut could slice a nerve or a tendon. To make the job
easier a Viennese inventor produced a spring-loaded lancet, called a
"Schnapper" in German or a phleam in English. It consisted of a case
about two inches long with a spring-loaded blade emerging from the top.
The bleeder would cock the blade, press the Schnapper against the skin
and push a release, causing the blade to snap down and across. The
Schnapper had the safety feature of not cutting beyond a certain depth.
Sometimes phlebotomists would use a scarificator -- a spring-loaded box
containing anywhere from twelve to eighteen blades. This tool was often
used in conjunction with "cupping" to relieve local inflammation. The
bleeder would place a glass cup against the skin and warm it with a
torch. The heat would create a vacuum strong enough to raise a large
blood-filled blister. The bleeder would pull off the cup, spring the
scarificator, and then reapply the cup to draw out more blood.
12

Today we regard leeches as loathsome, but for centuries these bloodsucking creatures were a mainstay of medical care. Derived from the
Anglo-Saxon word loece, to heal, the leech was used as an adjunct to
bloodletting, in places too sensitive or confined for the lancet or other
blood-letting instruments e.g. the gums, lips, nose, fingers, or even "the
mouth of the womb," according to a medical text from 1634.
The common medicinal leech, Hirudo medicinalis, produces natural anticoagulants and anesthetics in its saliva, so patients bleed readily and
generally feel nothing during the procedure. Leeches became popular in
the 19th century -- so much so that the species became endangered in
Europe. In 1833 alone, French doctors imported 41,500,000 leeches.
Today leeches have found renewed utility in certain surgical procedures,
particularly after microsurgery. Doctors sometimes find it helpful, for
example, to use leeches to restore circulation to a re-attached finger, or to
portions of the skin following plastic surgery.
13

Barber-Surgeons
During the Middle Ages a new category of medical practitioner
emerged. The Pope had banned the clergy from performing
bloodletting (although they were welcome to receive it), and
physicians were discouraged by the fact that feudal lords could
have them executed in cases of malpractice. So bloodletting and
other minor procedures moved into the hands of barber-surgeons.
More craftsmen than medics, they established their own guilds
and competed for respectability with apothecaries and physicians.
They advertised with a symbol that endures to this day -- a red
and white striped pole. The pole represents the stick patients
would grab while being phlebotomized; the white stripes
represent the bandages and the red stripes, the blood.

14

Naam, leader of the armies of Ben-Adad, King of

Syria, afflicted with leprosy, consulted physicians,
who, in order to kill him, drew out the blood from
his veins and put in that of another

Dutton WF: Intravenous therapy: Its application in the modern practice of

medicine. FA Davis, Philadelphia, 1925.

15

Petro de Abano, C13th:

He who drinks of menstrual blood or that of a leper
will be seen to be distracted and lunatic, evil-minded
and forgetful, and his cure is to drink of daisies
powdered and mixed with water of honey, and to
bathe in tepid water and to copulate with girls
according to the law natural, and to play with pretty
girls and young boys; and the antidote is to eat
serpents whose heads and tails have been cut off with
the edge of a palm frond.

[Brown HM: The beginnings of intravenous medication. Ann Med Hist 1:177, 1917]

16

First Transfusion Myth

In 1492, Pope Innocent VIII is said to have
received, at the behest of a Jewish physician, a
transfusion of the blood of three ten year old boys,
each of whom was paid a ducat and all of whom
died. Probably the blood was drawn, but was
intended to be taken orally. Indeed, there is no
reliable evidence that the sickly pope accepted the
blood at all.
Terminally ill with
what was likely
chronic renal disease

This story has been told and retold over the last
half millennium. It is most likely apocryphal and
has the flavor of an early urban legend in its details
and its anti-semitic and anti-Catholic overtones.

[Villari P: The life and times of Giralamo Savanorola. T Fisher Unwin, London, 1888;
Lindeboom GA: The story of a blood transfusion to a pope. J Hist Med 9:455, 1954.
Gottlieb AM: History of the first blood transfusion but a fable agreed upon: The transfusion of blood
17
to a pope. Transfus Med Rev 1991;5:228-235. ]

Circulation
Understanding the concept of circulation was critical to
developing the reality of blood transfusion.
Ancient Greeks believed that blood was formed in the heart,
then consumed as it flowed out to the body in veins, while air was
passed from the lungs to the body in arteries.
Erasistratos (~270 BCE) envisioned the heart as a pump.
Galen (131-201 CE) proved that arteries contain blood, but
thought that blood was formed in the liver, not suspecting that
arteries and veins are attached.

18

Circulation
Andrea Cesalpino (1519-1603) used the term circulation
and believed that the veins and arteries were connected by
a fine vascular network.
William Harvey is generally credited with the discovery in
1613 (published in 1628) of the circulation of blood as we
know it today.

19

WILLIAM HARVEY
1578-1657

Bloods acts above all the powers of the elements and is

endowed with such notable virtues and is also the instrument
of the Omnipotent Creator, no man can sufficiently extol its
admirable and divine faculties. The heart is the mere organ for
its circulation and it clearly appears that the blood is the
generative part, the foundation of life, the first to live, the last
to die and the primary seat of the soul
20

Andreas Libavius, 1615

First to advocate transfusion, though not known to have actually
attempted to perform a transfusion.
Let there be a young man, robust, full of spirituous blood, and
also an old man, thin, emaciated, his strength exhausted, hardly
able to retain his soul. Let the performer of the operation have
two silver tubes fitting into each other. Let him open the artery of
the young man, and put it into one of the tubes, fastening it in.
Let him immediately after open the artery of the old man, and put
the female tube into it, and then the two tubes being joined
together, the hot and spirituous blood of the young man will pour
into the old one as it were from a fountain of life, and all of his
weakness will be dispelled. Now, in order that the young man may
not suffer from weakness, to him is given good care and food,
but to the doctor, hellebore.
21

In 1628, Giovanni Colle (Padua) suggested transfusion as a means

of prolonging life but did not do it.
In the mid seventeenth century, many infusion experiments were
performed.

In 1658, Christopher Wren and William Boyle performed

a series of experiments injecting various medicaments into
the veins of dogs utilizing a bladder with an attached quill
and then observing the effects.
Infusion solutions included wine, beer, opium, emetics,
water, nitric acid, and sulfuric acid.
Willis injected dyes into the blood vessels supplying the brain
in order to trace its vasculature (thus the Circle of Willis).
22

Richard Lower
(1631-1691)

Richard Lower is credited with performing, in

1665, the first authentic blood transfusion
(animal to animal).
He kept exsanguinated dogs alive by connecting
the carotid artery of the donor dog to the jugular
vein of the recipient dog with a quill.

23

During his few, intensely active, years with the Royal Society,
Lower did much of the work that established his reputation as
perhaps the best seventeenth-century English physiologist after
Harvey. He was concerned principally with 2 areas of investigation:
transfusion and cardiopulmonary function. His interest in both can
be traced to his days at Oxford, but the fame of his investigations
and owed a great deal to his association with the Royal Society.
Apparently transfusion was attempted at Oxford in the late 1650s.
Familiar with earlier attempts by Christopher Wren who tried to
convey medicinal liquors directly into the bloodstream using quills
and special bladders, Lower in 1661 expressed interest in using
similar procedures to transmit broth and other nutritive fluids into
the bloodstream. In a letter to Boyle dated 18 January 1661, Lower
expressed, his "fancy to try, how long a dog may live without meat,
by syringing into a vein a due quantity of good broth" and described
his intended procedure as follows: "I shall try it in a dog, and I shall
get a tin pipe made, about two inches long, and about the usual
bigness of a jugular vein, and hollow, which I may put into the vein."
24

By 8 June 1664, Lower was able to write to Boyle in London about

a more daring experiment: he intended to "get two dogs of equal
bigness [and] let both bleed into the others vein. ..." As Lower was
to explain retrospectively in his TRACTATUS DE CORDE (1669),
he was led from the broth experiment to the transfusion attempt by
observing how harmoniously the blood of different animals mixed
with various injected substances.
It was natural to "try if the blood of different animals would not be
much more suitable and would mix together without danger or
conflict." It is quite possible that Lower was influenced as well by
reports of discussions at the Royal Society late in 1663. At one of
these, Timothy Clarke had described his method of infusing certain
medicinal preparations directly into the veins of dogs, and an
unnamed fellow of the society proposed "to let the blood of a lusty
dog into the veins of an old one, by the contrivance of two silver
pipes fastened to the veins of such two dogs."
25

 With his ideas crystallized, it took Lower only a few months to

perfect the requisite experimental technique. He performed the
first successful transfusion at Oxford late in February 1665,
transfusing blood "from an artery of one animal into a vein of
a second." The Royal Society soon heard of these results, and
in early 1666, after several months interruption due to plague
and the London fire, society members were busy making their
own investigations into transfusion.
In June 1666 John Wallis, who had been present at Lower's
successful experiment at Oxford the previous February,
reviewed Lower's success; and the society, through Boyle,
requested a full account from Lower. This was officially
received in September, replicated at the society in November,
and printed in PHILOSOPHICAL TRANSACTIONS
(December 1666). By mid-1667 Lower had joined the society.
26

27

The most probable ufe of this Experiment may be conjectured to be that one animal may live with the blood of
another; and confequently, that thofe animals, that want
bloud, or have corrupt bloud, may be fupplied from other
with a fufficient quantity, and of fuch as is good, provided
the Tranfufion be often repeated, by reafon of the quick
expence that is made of the bloud.
[Lower R: Philosophical Transactions Royal Society London [Biol] 1:353, 1666]

The importance of Lower is that he was the first to define the appropriateness of transfusional replacement of blood in severe hemorrhage.
28

Samuel Pepys, November 14, 1666.

Dr Croone told me that, at the meeting at Gresham
College tonight, there was a pretty experiment of
the blood of one dog let out until 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
but, as Dr Croone says, may if it takes, be of
mighty use to mans health, for the amendment of
bad blood by borrowing from a better body
29

Lowers report of human transfusion, Nov 23rd, 1667

30

Samuel Pepys, November 21, 1667.

they discourse of a man that is a little frantic, that
hath been a kind of ministera poor and debauched
man, that the College have hired for 20s to have
some blood of sheep let into his bodypropose to let
in about twelve ounces, which they compute which is
what will be let in in a minutes time by a watch
differ in the opinion they have of the effects of it;
some think it may have a good effect on him as a
frantic man by cooling his blood; others that it will
not have any effect at all
31

Samuel Pepys, November 30, 1667.

I was very pleased to see the person who had his
blood taken out. He speaks very well and this day
gave 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 the head,
though he speaks very reasonably and very
wellthe first man that ever had it tried upon him
in England, and but one that hear of in France,
which was a porter hired by the Virtuosos
32

Meanwhile, in Paris, Denis -- without proper citation

-- had appropriated Lower's techniques and
applied them to human transfusion. The Royal
Society was outraged and Lower, sensitive to his
colleagues' concerns, tried and succeeded at
human transfusion. On 12 December 1667 the
procedure was firmly established in England with
its second successful trial, this a public one before
a large crowd.

33

Jean Baptiste Denis

Denis was a young physician of Louis XIV. He preferred

animal (rather than human) blood for his experiments, as he
believed it less likely to be rendered impure by passion or vice
Denis and Emmerez performed transfusion of lamb blood into
the carotid artery of a young woman in June 1667.
Denis reported that the woman passed urine as black as soot
following the transfusion, a finding indicative of a hemolytic
transfusion reaction, but she survived.
34

Denis was born in Paris, in the 1640s, son of a hydraulic engineer who was
Louis XIV's chief engineer in charge of the works distributing the water of
the Seine from the pumps at Marly to the fountains at Versailles.
Denis is said to have studied medicine at Montpellier, but no records of this
can be found in the very complete archives of the Faculty of Medicine.
Niceron says that he obtained "un bonnet de Docteur en cette Facult" and
that "il fut aggrg la Chambre Royale". On the other hand, Martin de la
Martinire, who was a physician in ordinary to the king, in a letter to Denis
accuses him of taking the title of "matre" because of a "lettre de Mdecine"
that he obtained in Rheims. Nothing has yet been found in Rheims indicating
that he obtained such a degree. In Paris he taught philosophy & mathematics,
assuming the title of professor, which he placed at the head of his works. No
evidence for a degree in mathematics or philosophy has yet been found.
Beginning in 1664, Denis gave public lectures in physics, mathematics, and
medicine at his home on Quai des Grands-Augustins in Paris, and published
these lectures as conference reports. He also joined the group surrounding
Habert de Montmort, which met to discuss the new philosophy, much like
the groups in London that preceded the Royal Society. When the Acadmie
des Sciences was established in 1666, the Montmort group did not
35
participate and continued its own meetings.

The discovery of the circulation of blood by William Harvey had

stimulated experiments on the circulation. This was followed by the first
trial of transfusion of blood in animals. After discussions at the Royal
Society in England as early as its public meeting of 17 May 1665, an
account of successful transfusion in dogs was given by Richard Lower in a
letter written to Robert Boyle on 6 July 1665 and submitted by Boyle to
the Royal Society. This led to another successful transfusion in November
1666 at the Royal Society.
When reports of the English experiments reached Paris late in 1666 or
early in 1667, the Acadmie des Sciences immediately set about repeating
them, appointing a committee including Louis Gayant, an anatomist;
Claude Perrault, the physician noted for the east facade (the Colonnade) of
the Louvre; and Adrien Auzout, the astronomer. Gayant performed the
first transfusion in Paris on 22 January 1667, using dogs. Transfusion also
attracted the interest of the Montmort Academy, which apparently
appointed Denis and Paul Emmerez, a surgeon from St.-Quentin, to carry
out independent studies. On 3 March 1667 Denis performed a transfusion
experiment on two dogs. On 2 April 1667 various experiments involving
transfusion from three calves to three dogs were made. These were
published in the Royal Society's PHILOSOPHICAL TRANSACTIONS.
36

But it was the transfusion of blood in men which was of the greatest interest
to Denis, gave him his celebrity, and started the greatest medical controversy of that time. In these experiments he was assisted by Paul Emmerez.
The first transfusion of blood in man was made on 15 June 1667, on a
drowsy and feverish young man. From a lamb he received about twelve
ounces of blood, after which he "rapidly recovered from his lethargy, grew
fatter and was an object of surprise and astonishment to all who knew him".
The second transfusion was carried out on a forty-five-year-old chair bearer,
a robust man who received the blood of a sheep. He returned to work the
next day as if nothing had happened to him.
The recipient of the third transfusion was Baron Bonde, a young Swedish
nobleman who fell ill in Paris while making a grand tour of Europe. He was
in such a bad state that he had been abandoned by his physicians; and in
despair, having heard of Denis's new cure, his family asked Denis to attempt
transfusion of blood as a final recourse. After the first transfusion, which
was from a calf, Bonde felt better and began to speak. This improvement
lasted only a short time, however, and he died during a second transfusion.
37

The fourth transfusion patient was a madman, Antoine Mauroy, who died
during a third transfusion. He may have been poisoned by his wife, who,
perhaps to divert suspicion from herself or at the suggestion of the many
Paris physicians antagonistic to Denis, accused Denis of having killed her
husband. Denis brought the case before the court, and a judgment tendered
on 17 April 1668 cleared him of any wrongdoing but forbade the practice
of transfusion of blood in man without permission of the Paris Faculty of
Medicine. Meanwhile, another transfusion had been made by Denis, on 10
February 1668, on a paralyzed woman. After this, however, the practice of
transfusion faded out as suddenly as it had begun.
In 1673 Denis was invited to England by Charles II, who wished to learn
about transfusion and other remedies purportedly discovered by Denis. He
went to England and successfully treated the French ambassador and
several personalities of the court. Despite offers to remain, he became
dissatisfied and returned to Paris, where he continued his interest in
science and mathematics but never practiced medicine or again concerned
himself with transfusion. He died suddenly on 3 October 1704.
38

39

Denis fourth transfusion recipient, suffering from luetic madness, following a

symptom-free first transfusion of calf blood (December 19, SundayGregorian
calendar), developed a hemolytic reaction upon his second transfusion:

Wednesday: As soon as the blood began to enter into his veins, he

felt ...heat along his arm, and under his arm-pitsHis pulse rose
presently, and soon after we observed a plentiful sweat over all his
face. His pulse varied extremely at this instant, and he complained of
a great pain in his kidneys, and that he was not well in the stomach,
and that he was ready to choke unless they gave him his libertyhe
vomited of bacon and fatHe found himself urged to urine and asked
to go to stool When he awakeneda general lassitude he felt in all
his limbsHe made a great glass full of urine, of a color as black as
if it had been mixed with soot of chimneyhe bled at the nose very
plentifully Saturday morninghis urine cleared up and after that
time it resumed little by little its natural color

Seemed improved, so another transfusion done which proved fatal

40

Gregorian calendar
24 Feb 1582; Gregory VIII
(i) Mean year in Julian calendar a little too long and
vernal equinox had drifted back in the calendar year
and (ii) because the lunar year was used to calculate
Easter, there was a compounding error.
Deleted 10 days: Thursday 4 October 1582 was
followed by Friday 15 October 1582.
But European countries took varying times to
implement e.g. Venice in 1582, England only in 1752.
So what date to use???
41

Animal to Human Transfusion

Early lamb blood transfusion

Engraving by Scultetus, 1693, Armamentarium Chirurgicum, Leyden
42

43

44

45

46

47

Prohibitions against Transfusions

Mauroys wife charged Denis with poisoning her husband.
Denis was exonerated (and the wife was charged with
attempting to poison her husband!), but this incident led to
prohibitions against blood transfusions:
1678 prohibition by the French Parliament
The British Royal Society (1678), and
the Vatican (1679).

These prohibitions and the fear of adverse reactions led

to a 150-year near-complete hiatus in transfusion work.

48

The Eighteenth Century

Transfusions done only sporadically; generally animal to human.
Transfusion generally thought of as a cure for mental aberration or
as youth potion for the aged, rather than treatment for blood loss.
Reciprocal transfusions between husband and wife suggested as a
cure for marital discord.
Blood thought to carry characteristics of the donor to the recipient:
sheep blood would make a dog grow wool, hooves and horns;
cat blood would make a girl feline, etc.

[Brown HM: The beginnings of intravenous medication. Ann Med Hist 1:177, 1917]
49

James Blundell
In 1818, James Blundell
(obstetrician, Guys Hospital,
London) attempted human-tohuman transfusion.
He preferred human donors:
What is to be done in such
an emergency? A dog might
come when you whistled,
but the animal is small; a
calf might have appeared
better suited for the purpose,
but then it has not been
taught to walk properly
up the stairs.
50

Report of Blundells first transfusion, in the Lancet

Between 1825 and 1830 he performed 10 transfusions, five beneficial.
51

James Blundell
Although the possibility of transfusing whole blood from human to human
had been discussed in the literature for centuries, Blundell made the
hypothesis a reality. He completed four successful transfusions out of slightly
more than twice this number. As he pursued his experimental trials in dogs,
he performed, with a syringe, the first transfusion in humans in 1818.
Complicated instruments were described subsequently.
One device named an "Impellor" provided blood under pressure to the
recipient; the Gravitator, a gravity feed apparatus, was described in the
LANCET in 1829.
The indications for transfusion included postpartum hemorrhage, extreme
malnutrition, puerperal fever, cancer of the pylorus, ruptured uterus, and
hydrophobia. Since each of his patients was critically ill at the time of
decision, it is impossible to discover from the clinical notes whether a
transfusion reaction appeared as a complication in any. Excerpts from the
52
LANCET report follows:

In the present state of our knowledge respecting the operation, although it has
not been clearly shown to have proved fatal in any one instance, yet not to
mention possible, though unknown risks, inflammation of the arm has certainly
been produced by it on one or two occasions; and therefore seems right, as the
operation now stands, to confine transfusion to the first class of cases only,
namely, those in which there seems to be no hope for the patient, unless blood
can be thrown into the veins.
The object of the Gravitator is, to give help in this last extremity, by transmitting
the blood in a regulated stream from one individual to another, with as little
exposure as may be to air, cold, and inanimate surface; ordinary venesection
being the only operation performed on the person who emits the blood; and the
insertion of a small tube into the vein usually laid open in bleeding, being all the
operation which it is necessary to execute on the person who receives it.
Although the description of the instrument must appear complex, its use is
simple; in truth, when the transfusion is once begun, the operator has little to do;
his principal cares are -- first, to see that the cup never empties itself entirely,
otherwise air might be carried down along with the blood. Secondly, to make
sure that blood which issues by dribbling, from the arm of the person who
supplies it, may not be admitted into the receiver, as its fitness for use is
doubtful. Thirdly, to watch the accumulation of blood in the receiver, and to
prevent its rise above the prescribed level; and, lastly, to observe with attention
the countenance of the patient, and to guard, as before stated, against an
overcharge of the heart. This latter cause is of great importance.
53

James Blundell

Blundells transfusion devices included the impellor (A),

which consisted of a cup, tube , and syringe; and the
gravitator (B), consisting of a receptacle held high above
the patient with an attached tube through which the blood
was injected into the patient.
54

Following transfusion of a woman with postpartum hemorrhage with her husbands blood,
after six ounces had been administered, the
woman, previously semicomatose, suddenly
exclaimed By Jesus, I feel as strong as a bull

Doubleday E: Lancet 1:111, 1825

55

In 1849, Routh reviewed all the transfusion patients to that

date.
48 reported cases, of which 18 had had a fatal outcome,
which he estimated was rather less than that of hernia, or
about the same as the average amputation
Routh C: Med Times 20:114, 1849

Two instances of successful transfusion, both administered

during leg amputation, are documented from the Civil War.
56

1867
Uses antiseptics to
control infection
during transfusions

Joseph Lister, Lord

1827-1912
Founder of aseptic surgery

57

The Nineteenth Century

Transfusions in the 1800s were plagued by the complications
of transfusion reactions.
Panum and Landois showed that same species transfusions
were more efficacious than interspecies transfusions.
Landois noted that in interspecies transfusion red blood cells
were hemolyzed and white blood cells would cease their
amoeboid motion and die.
Nonetheless, animal to human transfusions were performed as
late as 1890.
58

59

Advances in technology

1873

60

61

In 1875, Landois*, in a comprehensive monograph on transfusion, collected 347

cases in which human blood had been used and 129 cases in which animal blood had
been used. By this time, important studies on the physiology of the blood were being
performed by a number of qualified observers, and some physicians, such as
Fordyce Barker, advocated transfusion " ... not exclusively in those desperate cases
where favorable results are hardly looked for but ... before patients have arrived at,
and fallen into, this desperate condition."
Techniques in use included transfusion with defibrinated blood, mediate transfusion
with pure blood, immediate transfusion from vein to vein, and immediate transfusion
from artery to vein.
Although the indications and rationale of blood transfusion were by this time
apparently quite well understood, the indications during the last quarter of the
century again became vague and irrational, the procedure was employed
indiscriminately, and the number of severe reactions and fatalities increased. As a
result, transfusion again began to be considered as a hazardous, and even a
disreputable, procedure, to be employed only as a last resort and in desperation.
*Landois, L.: DIE TRANSFUSION DES BLUTES. Leipzig: F. C. W. Vogel, 1875.
From BLOOD PROGRAM IN WORLD WAR II (SUPPLEMENTED BY EXPERIENCES IN THE KOREAN WAR)
by Douglas Blair Kendrick. Washington, D.C.: Office of the Surgeon General, Department of the Army, 1989. (Provided
by the Office of Medical History, Office of the Surgeon General/US Army Medical Command.)
62

Human blood only should be employedWhen lambs

blood is used, an invariable result seems to be the
escape, through the kidneys, of haemoglobin

Fagge & Pye-Smith, Textbook of Medicine, 1891

63

Anticoagulation:
Bischoff, 1835, proposed using defibrinated blood. Brown-Sequard
also experimented with defibrination in the 1850s. Accomplished by whipping or
twirling the blood, then removing the clot and transfusing the remaining fluid.

Neudorfer, 1860, used sodium bicarbonate

Braxton-Hicks, 1868, used Na phosphate

But transfusion was generally by:

Artery to vein cannulation

Paraffin-coated tubes

64

Direct transfusion (artery to vein for speed) advocated

65

1908:
French surgeon Alexis Carrel devises a way to prevent
clotting by sewing the vein of the recipient directly to the
artery of the donor. This vein-to-vein method practiced
by a number of physicians, but was impractical.
(Did pave the way for organ transplantation, for which
Carrel received the Nobel Prize in 1912)

66

The Kimpton-Brown
transfusion apparatus was
commonly used before
citration. It consisted of a
paraffin-coated gradient glass
cylinder with a horizontal
side tube for suction. It was
in use until approximately 1918.

67

The Nineteenth Century

Saline used as blood substitute in 1884.
Saline infusion was observed to be safer than, and frequently as
effective as, blood transfusion.
Milk was advocated as a potentially effective infusion, because
it was thought that the white corpuscles of milk were capable
of being transformed into red blood corpuscles.
Because of difficulty with coagulation, milk was used extensively
as a blood substitute in the USA in the final quarter of the C19th

68

The complications of transfusion and logistical problems

in obtaining blood led to a search for safer, more readily
available substitutes. For example,
James Bovell & Edwin Hodder (Canadian Journal, 1855)
transfused fresh cows milk for treatment of patients
during the cholera epidemic in Toronto in summer of 1854.

in a few seconds the pulse was distinctly feltalmost

simultaneously, the eyes andthe lungs responded to the
vital tide which now flowed toward themthe voice,
which was unearthly before, was clear

69

Gesellius, 1870s, capillary blood donation

70

Karl Landsteiner
1930 Nobel Prize Laureate

In 1900, Landsteiner showed that serum from some

individuals could agglutinate or hemolyze the red
blood cells of certain, but not all, other individuals.
The serum of the latter would likewise agglutinate the
red blood cells of the former. Still other individuals
red cells were unaffected by the serum from either of
these. He named these three different types A, B, and
C. Today these are types A, B, and O.

71

K. Landsteiner: Zur Kenntnis der antifermentativen, lytischen und

agglutinierenden Wirkungen des Blutserums und der Lymphe. Centralblatt fr
Bakteriologie, Parasitenkunde und Infektionskrankheiten. 1900, 27: 357-362.
This paper contains the perhaps most famous footnote in the history of medicine:

"Das Serum gesunder Menschen wirkt nicht nur auf tierische Blutkrperchen
agglutinierend, sonders fters auch auf menschliche, von anderen Individuen
stammende. Es bleibt zu entscheiden, ob diese Erscheinung durch
ursprngliche
individuelle Verschiedenheiten oder durch die erfolgte Einwirkung von
Schdigungenetwa bakterieller Natur ist."

"The serum of healthy people does not only act on agglutinating animal
blood corpuscles, but often also on blood from other individuals. It
remains to decide whether this is caused by natural, individual
differences or as a consequence of damage of some bacterial nature.
72

73

74

Compatibility testing
Landsteiner pointed out the importance of his findings in
his original paper (1900)
Ottenberg and Schultz were the first to apply this information
in an actual transfusion (1907)
In 1911, Hektoen suggested that blood groups be made the
basis for selection of donors for blood transfusion.
World War I experiences led to the universal adoption of
blood typing to select blood donors.

75

Reuben Ottenberg

Appointed the George Blumenthal, Jr. Fellow in pathology in 1908, Dr.

Reuben Ottenberg served Mount Sinai Hospital with distinction for 50 years
and became one of its most productive physicians in the first half of the 20th
century. Born in New York, Ottenberg received his B.A. from Columbia
University in 1902 and his M.D. degree from the College of Physicians and
Surgeons three years later.
Ottenberg's first paper, "Transfusion and Arterial Anastomosis" (ANNALS
OF SURGERY, 1908), won the prize for the best paper of the year by a
member of the house staff. Ottenberg describes an experimental study of
performing sutureless arterial anastomoses utilizing tiny silver rings held in
place by silver wire, rather than sutures, in animals for use in direct
transfusion and then describes its use in two patients being transfused. He
notes that the blood was tested for compatibility prior to use; the first report
anywhere of the clinical use of compatibility testing. Years later Dr.
Ottenberg was to note, "The subject is only brought in incidentally in a
footnote. I was still an intern and did not realize how important the testing
was to become. I should have made a separate article."
76

In 1923, Ottenberg reported that jaundice and hemolytic anemia of the

newborn might be due to blood incompatibility of mother and child.
Landsteiner's & Levine's discovery of the Rh factor almost 20 years later
proved Ottenberg correct. He was also the first to suggest that human blood
groups are inherited according to Mendel's law, and described a new
method of counting platelets using sodium citrate, a technique that
remained in standard use for decades.
Ottenberg also wrote important papers based on his clinical work, including
on the diagnosis of painless jaundice, the toxic effect of sulfonamides, and
septicemia following trauma. Suffering from stenosis of the internal carotid
artery, Ottenberg reported his own case in 1955, four years before his
death. In a matter of fact manner, he described his TIAs, his episodes of
amaurosis fugax, and the stroke from which he recovered.
In 1954, Ottenberg received the Karl Landsteiner Award of the AABB for
distinguished pioneering contributions to blood banking & hemotherapy.
After noting his many contributions the award went on to state Everyone
of these were milestones in the growth of our knowledge of blood groups
and formed the basis for the subsequent development of blood transfusions
77

 1908
Moreschi: the antiglobulin reaction

78

Blood Typing
Sturli and DeCastello described the fourth blood group,
AB, in 1902.
Levine and Stetson, in 1939, describe a severe reaction in a
Type O woman given a transfusion of her husbands Type O
blood following a stillbirth. Her serum agglutinated 80% of
Type O blood.
Landsteiner and Wiener, in 1940, describe Rh typing. This
leads to dramatic decrease in the incidence of hemolytic
disease of the newborn.
Over 250 different antigens categorized into 23 major discrete
systems are now known.
79

Number of red cell antigens known

240

To Sept 1,
1969 = 249

200

150

100

50

30
20

10
1900

1940

year

1960

80

81

Hangover is more pronounced in persons of group A;

members of group B defecate the most (Warnowsky, 1927)
Increased incidence of group B among criminals (Bohmer
1927)
Persons of group O have the best teeth, followed by AB,
while A and B persons have the worst (Suk, 1930)
Group O individuals have less satisfactory strength of
character and personalitygroup B individuals are
impulsive (Schaer, 1941)
Other associations were made with homosexuality,
lesbianism, platonism, sadism and flat feet.
82

Wood et al, Nature, 1972

Anopheles Gambiae (species A from Nkolmekok,
Cameroon) is selective in its feeding habits: extracted
blood from mosquitos gut and typed it.
Persons who are group O had a mean of 5.045 bites on
their forearms; persons who are group A had a mean of
3.276 bites

Giles et al, Nature, 1973

Group A2 highest IQ, then group O, then A1 phenotype

83

Statistical association of ABO blood groups with disease:

Malignancy:
stomach, colon, rectum, salivary glands, uterus, cervix, ovaries
Other diseases:
pernicious anemia, cholecystitis, rheumatic disease, peptic ulcer

Loss of ABH antigens from malignant cells

Appearance of new and illegitimate ABH/Lewis/Ii antigens on
malignant cells
Association of ABH/Lewis/Ii antigens with CEA
Association of ABO with bleeding and with clotting
Bacterial infections (also other blood group associations)

84

Proven relationships of blood groups with disease:

Hemolytic disease of the newborn/fetus
Autoimmune hemolytic anemia
Hemolytic transfusion reactions
Graft rejection and ABO antibodies
Early abortion and P system antibodies

Neonatal/fetal alloimmune thrombocytopenia

Post-transfusion purpura
85

RBC morphology

Transmembrane protein

Acanthocyte

Kx polypeptide
Lutheran polypeptide

Elliptocyte

glycophorin C and D

Stomatocyte

Rh polypeptides

Urea transport and Jk(a-b-) phenotype

PNH and glycosylphosphatidylinositol (GPI)-anchored proteins
(Cromer, Gya, Hy, Yta, JMH, Doa and Dob
Intestinal disorders and Inab phenotype
SLE and Chido-negative, Rogers-negative phenotype
Malaria resistance with the Fy(a-b-) phenotype

86

In Japan: Toronto Star, 26 June, 1991

Type A:

cautious, eager to please, indecisive,

sympathetic and conformist

Type B:

decisive, known for originality and

versatility, are occasionally obnoxious
and stand out in a crowd

Type O:

produces team leaders, confident and

cool-headed people, who meet
challenges with courage, but may be
domineering and moody

Type AB

blood is said to produce complex,

mysterious folks with tendency to
eccentricity and talent for specialized fields
87

Lewisohn
In 1913, Richard Lewisohn, a surgeon at the Mount Sinai Hospital,
introduced the modern technique of blood transfusion, developed from
his discovery of a method of preventing coagulation of the blood
outside the body. Dr Howard Lilienthal, who performed the first
transfusion on a human using Lewisohn's citrate method, wrote: The
ease and simplicity of this transfusion was most amazing to me, who
had so often suffered more than the patient in performing this lifesaving operation.
Lewisohn was educated in Germany and received his medical degree
from the University of Freiburg in 1899, with a doctors thesis on
"Malignant Tumors of the Kidney." In 1906, he immigrated to New
York, and after obtaining his medical license, joined the staff of the
Mount Sinai Hospital. He retired in 1937.
88

Anticoagulation:
1914, 1915: sodium citrate as anticoagulant:
Belgium, Argentina, New York (Lewisohn)
1915:

refrigeration

1916:

Rous & Turner: salt, citrate, glucose solution

1940s:

minor modifications by DeGowin, Alsever, etc

1943:

Loutit & Mollison: ACD; adopted by the army

in 1945

WWI: O Robertson: creates blood depots: 1st blood bank

89

First World War posters

90

Oswald Robertson
After his house officership he was appointed as an assistant in bacteriology
and pathology at the Rockefeller Institute for Medical Research, where he
planned to continue his studies on the physiology of blood in the
laboratories of Peyton Rous. He moved to New York in the autumn of 1915,
but he had barely started his experiments on reticulocytes when World War
I called for his services on the Harvard team of Dr Harvey Cushing. In
France, his early interests in hematology stood him in good stead as he was
assigned the task of seeking better ways of reducing the risks of excessive
transfusions. At the same time he initiated experiments to learn whether a
fluid devised by Rous in the laboratory to preserve human blood cells "in
vitro" had a practical use for transfusions at the battle front and in military
hospitals. He demonstrated that the preserved cells were indeed an
acceptable substitute, and Robertson now is recognized as the creator of the
first blood bank. For this work he received decorations from both the
American and British governments and was discharged in 1919 from the
U.S. Army after attaining the rank of major.
91

Early transfusions
were a complex affair

First transfusion St. Michaels Hospital, Toronto, 1917

92

Percy Oliver
In October 1921, in his capacity as honorary secretary of the Camberwell Branch
of the Red Cross, he received a telephone call from nearby King's College
Hospital. They were in urgent need of a blood donor and sought his help. He and
a few colleagues went to the hospital, and from them Sister Linstead, a Red Cross
worker, was chosen, becoming the first voluntary blood donor.
The results of this exercise so impressed Oliver that with the help of his wife he
set about devising and organizing a system for a panel of donor volunteers. The
donor's health and blood details were checked by the hospital and kept on record
cards in his home, where there was continuous telephone cover. In the first year
there were 4 members of the panel and they had one call; 5 years later there were
400 members and > 700 calls. Oliver was convinced that organized panels of
volunteer donors were the answer and he worked hard at setting up similar panels,
particularly in London, with the help of groups such as St. John Ambulance and
the Rover Scouts. To cope with the organization and the paper-work it was also
necessary to move to a larger house -- 5 Colyton Road, Camberwell. Much of his
free time was spent travelling around the country, explaining the system, and
encouraging the formation of yet more local groups of volunteers.
93

Although on its inception in 1921 Oliver called it the London Blood

Transfusion Service, it was really a voluntary donor service for local
hospitals. It progressed to the stage where the official support of the British
Red Cross Society was considered essential. This was forthcoming and in
1926 it became the British Red Cross Blood Transfusion Service, later
changed to the Greater London Red Cross B.T. Service and eventually
developed into the National Blood Transfusion Service. General hospitals
were not charged for the service and no payment was ever made to, or
expected by, the donors. The expenses of running the organization from the
house in South London were met by charging private clinics, by grants from
institutions, and by Oliver's own efforts.
Oliver had the support of many eminent surgeons and doctors, but there
were others who resented this intrusion into medical preserves by a layman.
Many donors had to keep their involvement secret from families and
employers, and as recently as 1940 Percy Oliver was still travelling the
country trying to dispel apprehensions and encourage the supply of donors
and the setting up of panels.
94

Oliver's work attracted attention worldwide and many countries sent

representatives who sought and acted upon his advice on setting up similar
organizations. In 1937, an exhibition at a meeting of the Voluntary Blood
Donors Association featured the idea of stored blood which, although
originally used by Canadian doctors in the First World War, had been
brought to the fore in the Spanish Civil War. This was to become the basis
of the war-time blood bank which Oliver helped to create at Luton in 1939.
Surprisingly, Oliver received no official recognition for his work in the
development of voluntary blood donor panels, although in later years he was
invited back to Buckingham Palace to talk with the King about his work.
Percy Lane Oliver died on April 16, 1944, but his achievements are not
forgotten. A memorial consisting of a portrait and a panel with an
appropriate inscription was unveiled in the entrance hall of the hematology
department of King's College Hospital, London, in 1972 by Her Royal
Highness The Duchess of Gloucester. A framed copy of this is in every
Regional Transfusion Centre in Britain, and another is in the Donor Centre
in Rome, bearing a suitable translation. In 1979 the Greater London Council
provided an appropriate plaque on the house in South London where so
much of Oliver's work was undertaken.
95

More advances

96

Alternative sources of blood:

Cadaver blood, Russia, 1938
Placental blood, Lancet, 1939

97

o First Blood Bank formulated in Leningrad in 1932

o First functional blood bank in Barcelona, 1936
o First transfusion service in the field: Spanish Civil
War, 1937-1939 [Norman Bethune] .

..

98

Born: March 3, 1890 in Gravenhurst, Ontario, Canada

Died: November 12, 1939 in Huang Shikou, Heibei, China
Bethune's death received little attention in Canada or in China
until the Cultural Revolution (1966-1976). During that decade of
social and political upheaval the Chinese Communist leadership
used Bethune as a symbol of selflessness, dedication, and
responsibility -- characteristics that they wanted the Chinese
people to adopt. They published hundreds of millions of copies of
an essay written by Mao Zedong called "In Memory of Norman
Bethune." Everyone was expected to read it, and many committed
it to memory. Since the 1960s through books, movies, and study
in the schools, Bethune has become a national hero in China.
In Canada, belated recognition was granted in 1972 when the
federal government declared him "a Canadian of national
historical significance." The Presbyterian manse in which he was
born was restored to period and a portion of it converted into a
museum. It was opened in 1976 as the Bethune Memorial Home.
99

1940: Edwin Cohn at Harvard develops cold ethanol

fractionation, allowing separation of plasma
components e.g. albumin, globulin, fibrinogen.
1940: Charles Drew develops the Plasma for
Britain program in the USA.

100

Overview of Material Flow

Donor
screening

Fractionation Process

Plasma
(1000 kg)

Cold liquid ethanol, varying ionic strenth, pH,

temperature, ethanol concentrations, protein
concentration, chromatography

Cryo
(5.7%)

Fr. I
(7.3%)

Fr.
II+III
(25%)

IgG 7 kg

Fr. IV-1
(13%)

Alpha 1-PI0.6 kg

Fr. IV-4
(10%)

Fr. V
(40%)

Albumin 32 kg

Purification Processes
chromatography, viral inactivation, stabilizers
F. VIII 0.1 g*
IgG 3 kg Alpha 1-PI 0.3 kgAlbumin 24 kg
101
* Numbers are industry average (estimates)

 Charles R. Drew was a renowned surgeon, teacher, and

researcher. He was responsible for founding two of the world's
largest blood banks. Because of his research into the storage and
shipment of blood plasma -- blood without cells -- he is credited
with saving the lives of hundreds of Britons during World War
II. He was director of the first American Red Cross effort to
collect and bank blood on a large scale. In 1942, a year after he
was made a diplomat of surgery by the American Board of
Surgery at Johns Hopkins University, he became the first African
American surgeon to serve as an examiner on the board.

102

In 1928 he was finally able to apply to medical school. However, African

Americans who wished to become doctors at that time did not have many
opportunities. There were two colleges open to them. Drew applied to
Howard University and was rejected because he did not have enough
credits in English. Harvard University accepted him for the following
year, but he did not want to wait so he applied to and was immediately
accepted to McGill University in Montreal, Canada.
At McGill, Drew continued to excel in sports and academics. In 1930 he
won the annual prize in neuroanatomy and was elected to Alpha Phi
Omega, the school's honorary medical society. During this time, under
the influence of Dr. John Beattie, a visiting professor from England, Drew
began his research in blood transfusions. The four different types of blood
-- A, B, AB, and O -- had recently been discovered. Subsequently, doctors
knew what type of blood they were giving to patients and were avoiding
the negative effects of mixing incompatible blood types. However,
because whole blood was highly perishable, the problem of having the
appropriate blood type readily available still existed. In 1930 when Drew
& Beattie began their research, blood could only be stored for seven days.
103

 In 1933 Drew graduated from McGill with his Medical Degree

and Master of Surgery degree. He interned at the Royal Victoria
Hospital and finished his residency at Montreal General. During
this time, he continued researching with Beattie.
Because of his father's death in 1934, Drew decided to return to
Washington, D.C., to take care of his family. In 1935 he accepted
a position to teach pathology at Howard University Medical
School. The next year he obtained a one-year residency at
Freedmen's Hospital in Washington, D.C.

104

 In 1938, having accepted a two-year Rockefeller Fellowship, Drew

continued his work in blood at Columbia University-Presbyterian
Hospital in New York. Under the auspices of the Department of
Surgery, he worked with Drs John Scudder and EHL Corwin on the
problem of blood storage. Drew began to study the use of plasma as
a substitute for whole blood.
In 1939, while supervising a blood bank at Columbia Medical Center,
Drew developed a method to process and preserve blood plasma so
that it could be stored and shipped to great distances. (Dehydrated
plasma could be reconstituted by adding water just before the
transfusion.)

105

Drew graduated from Columbia University in 1940, with a Doctor of Science

degree, the first African American to receive this degree. In his dissertation,
"Banked Blood: A Study in Blood Preservation," Drew showed that liquid
plasma lasted longer than whole blood. He was asked to be the medical
supervisor on the "Blood for Britain" campaign, launched by the Blood
Transfusion Betterment Association. At the height of World War II, Nazi
warplanes were bombing British cities regularly and there was a desperate
shortage of blood to treat the wounded.

To meet the huge demand for plasma, Drew initiated the use of bloodmobiles
-- trucks equipped with refrigerators. In 1941 after the success of "Blood for
Britain," Drew became director of the American Red Cross Blood Bank in
New York. He was asked to organize a massive blood drive for the U.S.
Army and Navy, consisting of 100,000 donors. However, when the military
issued a directive to the Red Cross that blood be typed according to the race
of the donor, and that African American donors be refused, Drew was
incensed. He denounced the policy as unscientific, stating that there was no
evidence to support the claim that blood type differed according to race. His
statements were later confirmed by other scientists, and the government
eventually allowed African American volunteers to donate blood, although it
was still segregated. Ironically, in 1977 the American Red Cross headquarters
in Washington, D.C., was renamed the Charles R. Drew Blood Center.
106

o First blood bank in USA at Cook County in 1937 (actually

recently shown to be at the Mayo Clinic in 1935*)
o First large-scale blood transfusion service: World War II
o National Blood Transfusion Service in England: 1946

*Transfus Med Rev 19:241, 2005

107

Before 1939:
3 blood group systems ABO, MN, P
3 known plasma proteins albumin, euglobulin, pseudoglobulin
Complement was only a vague entity
No Coombs test

108

FIGURE 1-25. [A) Patrick

Mollison. (8) A 1947 photograph
taken at the Lister Institute in
London showing, from left to right:
Louis K. Diamond whose research
clarified the pathogenesis of
hemolytic disease of the fetus and
newborn as well as the optimal
management of that disorder;
Patrick L. Mollison, a pioneer in
the field of blood transfusion and
editor of ten editions of the famous
text, Blood Transfusion in Clinical
Medicine; Robert R. Race, an
eminent immunohematologist who,
along with his long-time
collaborator. Ruth Sanger. made
innumerable contributions to the
field of RBC genetics and serology;
and Sir Ronald A. Fisher. a famous
geneticistjbiostatistician who,
together with Race, devised a
classification of the Rh blood group
system that is still used. [Courtesy
of Professor P. L. Mollison.)
109

In 1939, red cell storage was 7 days (sodium citrate)

Extended to

21 days in ACD (1943)

28 days in CPD (1957)
35 days in CPD-adenine (1965)
49 days in Adsol (increased
glucose, mannitol)

1960s: Cryoprotective agents, e.g. glycerol, provide

the technology to freeze and reclaim cells i.e. longterm storage.

110

In 1939, there was just whole blood and plasma

The extension of blood component therapy was one

of the great advances of the last 50 years

111

Plastic Blood Bags

Blood was collected into reusable glass bottles in the
first half of the twentieth century. Whole blood was
transfused. Pyrogenic reactions from contamination due to
incomplete cleaning were frequent. Air embolism was a common
complication due to the vacuum systems used with glass bottles.
In 1949, trials of plastic bags were conducted by the American
Red Cross [Walter].
Plastic bags were disposable and, because of their flexibility,
facilitated the safe separation of blood components and the
advent of component therapy.
At least 17 different components are available through a blood
bank.

112

Preservation
ACD preservative was supplanted by citrate-phosphatedextrose (CPD) in 1957, CPD with adenine in 1965, and
CPD-A1 in the 1980s.
Effective preservation and refrigeration lead to the ability
to bank blood.
Cryoprotective agents, such as glycerol, gain use in the
1960s, enabling freezing of blood for long-term storage.

113

In less than 30 years, Rh hemolytic disease

of the newborn moved full cycle, from
hypothesis to prevention

114

Mid 1950s: In response to increased demand created by open

heart surgery and advances in trauma care, blood transfusion
enters its most expansive growth period.
1961: Platelet concentrates: reduces mortality in cancer patients
1969: Platelets stored at room temperature
1962: AHF to treat hemophiliacs
1965: cryoprecipitated AHF for hemophilia treatment
1967: Rh immune globulin commercially introduced for HDN
115

Major Innovations in the 20th Century

Compatibility testing
Anticoagulant preservative solutions
(1943: ACD: Loutit & Mollison: allowed reduced volume of anticoagulant, longer
storage and larger volumes of blood to be transfused;
1983: shelf life red cells 42 days)

Refrigeration
1945: Coomb, Mourant & Race: Antiglobulin test
Blood Banks (1947: AABB formed)
Plasmapheresis: for collecting plasma for fractionation (1964)
Plastic blood bags (Walter & Murphy, 1950)
Component administration
Infectious disease testing (1943: Beeson: transfusion-transmitted hepatitis;
1971: HBsAG testing begins)

High-risk donor screening (1985: HIV screening test; 1987: anti-HBc,116ALT)

The Spectrum of Hemotherapy

Progenitor Cells

Stem Cell

Long-term engraftment Short-term engraftment

Gene therapy

Mature Cells
Supportive therapy
Immunotherapy

Marrow
Cellular
components
Liver

Plasma
cells Igs

Plasma components
Blood

Biotechnology

Modified from
James Isbister

Cytokines, Plasma Components, ex vivo expansions 117

Ironically, it was when blood

banking became established and
accepted as the modus operandi for
the quality, safety and supply of
blood components that clinicians
and patients locked out of
transfusion medicine.
This resulted in knowledge,
expertise and research of
transfusion medicine moving away
from the patient and clinical
workface, focusing less on
pathophysiology of disease and
more on supply, safety and cost.
118

ISSUES

ial
c
n
i
v
o
r
$
ederal/P
F
SUPPLY
$
Politics

Administration &
Policy

Adequacy
Quality
Safety

Politics
Cost
effectiveness

Donors
CANADIAN
COMMUNITY

$
PNBC
SABM

Transfusion appropriateness ONTraC

Safety vs Efficacy
Blood Management

DEMAND

Industry
$
CBS/HemaQuebec
Donor & Recombinant
AUSTRALIA Blood
Components
N
Transfusion Alternatives

NATA

Surveillance

$ $

COMMUNIT
Y

Clinical / Laboratory services &

personnel
AUSTRALIA
Diagnosis
Therapy - Apheresis
N

$
$ $

$
hospitals
Professional
associations

CSTM
CHS

Private sector
Public sector Modified; with
COMMUNIT
Patient
health delivery
thanks 119
to James
Y Needs & Rightshealth delivery Isbister

21st century ???

Bloodless medicine/blood conservation/blood management
Artificial blood components and blood products
Pharmacologics
Error prevention
Adverse event prevention (including infectious)
Molecular techniques/nanotechnology
Proteomics/genomics

???

120

A brief history of transfusion

Jean-Baptiste Denis
1640 - 1704
Transfused humans with
Animal blood
June 15, 1667
1600

April 17, 1688

James Blundell*
1770-1878
Transfused humans with
human blood

Karl Landsteiner
Born 6/14/1868; died 6/26/1943
Discovered ABO and (with Levine)
Rh blood systems

1900
1800

TRANSFUSION BAN PERSISTED

FORBIDDEN
For 130 years!
By Paris Faculty of Medicine

1907

2000

First successful
ABO-matched
human-human
transfusion at
Mt Sinai hospital
by Reuben Ottenberg 121

*Relied strongly on Leacocks work in Caribbean