Transfusion Medicine: A History

Blood in the Bible

Leviticus 17:11
“…the life of the flesh is in the blood…”

Genesis 9:4
“Only flesh with the life thereof, which is the blood
thereof, shall ye not eat.”

Matthew 26
“…take drink…this is my blood, which is shed for you
for the remission of sins…”
 Blood in History
China, 1000 BC
The soul was contained in the blood.

Egyptians bathed in blood for their health.

Pliny and Celsus describe Romans drinking the blood of

fallen gladiators to gain strength and vitality and to cure epilepsy.

Taurobolium, the practice of bathing in blood as it cascaded

from a sacrificial bull, was practiced by the Romans.
 “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.

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.
 Pope Innocent VIII
“…a Jewish daring innovator,
whose name has not come
down to us in memory of
his deed, proposed to find
the pontiff a fountain of
jouvenance in the blood of
three youths who died as
martyrs to their own
devotion and the
practitioners zeal.”
Drinkard, 1870
 Andreas Libavius, 1615

He was the first person to advocate transfusion, though he is

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.”
 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 BC) envisioned the heart as a pump.

Galen (131-201 AD) proved that arteries contain blood,

but thought that blood was formed in the liver, not suspecting
that arteries and veins are attached.
 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

1616 (published in 1628) of the circulation of blood as we
know it today.
 Infusion Experiments

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).
 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.
 Jean Baptiste Denis

Denis and Emmerez performed transfusion of lamb blood into

the carotid artery of a young woman in 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.
Animal to Human Transfusion

Early lamb blood transfusion

Denis’s fourth transfusion recipient, suffering from luetic madness,
following a symptom-free first transfusion of calf blood,
developed a hemolytic reaction upon his second transfusion:

“As soon as the blood began to enter into his veins, he felt
...heat along his arm, and under his Arm pits…His pulse rose
presently, and soon after we observ’d 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 choak unless they gave him
his liberty…When he awakened…He made a great glass full of
urine, of a color as black, as if it had been mixed with the soot of
chimneys.”

His madness seemed improved, so another transfusion

was undertaken which unfortunately proved fatal.
 Prohibitions against Transfusions

This man’s 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 a
1678 prohibition by the French Parliament of further
transfusions. The British Royal Society (1668) and the Vatican
(1669) had also laid prohibitions against blood transfusions.

These prohibitions and the fear of adverse reactions led to a 150

year long near complete hiatus in transfusion work.
 The Eighteenth Century
Transfusions were done only sporadically, and were generally
animal to human.

Transfusion was generally thought of as a cure for mental

aberration or as a youth potion for the aged, rather than as a
treatment for blood loss.

Reciprocal transfusions were suggested as a cure for marital

discord.

Blood was thought to carry the 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.
James Blundell
In 1818, James Blundell
attempted human-to human
transfusion of a man
suffering from gastric
carcinoma.

“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.”
 James Blundell

Blundell’s 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.
 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.

However, animal to human transfusions were performed as

late as 1890.
 The Nineteenth Century

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.”

Two instances of successful transfusion, both administered

during leg amputation, are documented from the Civil War.
 Karl Landsteiner In 1900, Landsteiner
1930 Nobel Prize Laureate 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.
 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 husband’s 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.
Major Innovations in the 20th Century

Compatibility testing
Anticoagulant solutions
Preservative solutions
Refrigeration
Blood Banks
Venous access
Plastic blood bags
Component administration
Infectious disease testing
High-risk donor screening
 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.

Coombs described antiglobulin testing in 1945.

 Anti-coagulation
Blundell had observed the need for rapid transfusion in
order to prevent coagulation.

Direct transfusion (artery to vein for speed) was advocated.

 Anti-coagulation

In 1835, Bischoff proposed defibrination. Brown-Sequard

also experimented with defibrination in the 1850s. It was
generally accomplished by whipping or twirling the blood,
then removing the clot and transfusing the remaining fluid.

Neudorfer, in 1860, recommended sodium bicarbonate.

Braxton Hicks unsuccessfully used sodium phosphate.

Lewisohn (1914) used citrate. Weil noted that citrated blood

could be stored in the refrigerator for several days.
 Lewisohn’s Method of Transfusion

Blood is collected in a citrated flask….…...and immediately transfused.

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.
 Preservation

Furthering the work of Lewisohn and Weil, Rous and Turner

developed a solution of salt, isocitrate and dextrose in order to
both anticoagulate and preserve blood.

This mixture made the blood extremely dilute, so it had to

be removed prior to transfusion. (1:1 solution:blood ratio)

This method, with minor variations, was used through most

of World War II.

Loutit and Mollison introduced ACD (acid-citrate-dextrose)

as a preservative in 1943. It was adopted by the Army in 1945.
(1:4 solution:blood ratio)
 Preservation

ACD preservative was supplanted by citrate-phosphate-

dextrose (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.
 Blood Banks

During the Spanish Civil War, the Republican Army banked

9000 liters of blood later administered at casualty stations and
base hospitals.

Bernard Fantus, at Chicago’s Cook County Hospital,

established the first blood bank in the United Stated in 1937.

Blood banks now standard in communities and hospitals, with

regional blood centers collecting approximately 75% of the
blood supply for the United States.

13,588,000 units collected in the US in 1992.

 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 on glass bottles.

In 1949, trials of plastic bags were conducted by the American

Red Cross.

Plastic bags were disposable and, because of their flexibility,

facilitated the separation of blood components and the advent
of component therapy.

At least 17 different components are available through a blood bank.

Plastic Blood Bags and Component Separation
 Component Therapy

Every unit of blood can treat more people.

Revolutionized the treatment of Hemophilia A.

 Changes over Time

In 1943, Beeson described posttransfusion hepatitis.

The donor pool has changed from a frequently paid group

to an mandated voluntary donation system.

The worldwide pandemic of Human Immunodeficiency Virus.

Transition from Blood Banking to Transfusion Medicine.