26/05/24 1

HISTORY OF BLOOD
TRANSFUSION
HAEM VI
MLH 406
Mrs. Sheila Allotey
16TH APRIL, 2024
ATU
 26/05/24 HISTORY 2

Blood in History
China, 1000 BC
The soul was contained in the blood. ( Lev 17:11)

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.
26/05/24 HISTORY 3

“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.
26/05/24 4

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
26/05/24 5

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.”
26/05/24 6

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.
26/05/24 HISTORY 7

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.
26/05/24 HISTORY 8

Animal to Human Transfusion

Early lamb blood transfusion

 9

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.
26/05/24 HISTORY 10

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 (break) in transfusion work.
 11

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.
 12

James Blundell In 1818,

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.”
26/05/24 HISTORY 13

On September 26, 1818, a very historic

date, James Blundell visited a patient
named Brazier, who had carcinoma of the
stomach. He was at the point of death, and
James Blundell tried to revive him with blood
transfusions.
Several members of the family gave twelve
to fourteen ounces of blood to the patient.
Unfortunately, this was a poor case to try it
on.
26/05/24 14

He was almost dead then, and he died within

twenty-four hours after the transfusion-not
because of the transfusion, but nevertheless, he
died.
James Blundell tried transfusions on others,
and out of ten patients transfused, five died and
five lived.
Blundell was a very proud and arrogant man,
and had little respect for other people's ideas.
He was not very well liked.
Later he went to Paris, and when he came back
his hospital appointments had been taken
away.
26/05/24 15

But the last word was this.

“Some day the world would realize that
blood transfusions are use-ful.”

He had a considerable amount of money,

so he retired in a home near London,
where he had a huge library.
He became a recluse and nothing more
was heard of him in the field of research.
 16

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.
 26/05/24 HISTORY 17

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.
26/05/24 HISTORY 18

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.
26/05/24 19

Karl Landsteiner In 1900, Landsteiner

1930 Nobel Prize Laureate showed that serum from
some individuals could
agglutinate or haemolyse
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.
 20

Blood Typing
Sturli and DeCastello described the fourth blood group,
AB, in 1902.

Levine and Stetson, in 1939, described 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, described 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.
26/05/24 21

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
 26/05/24 22

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.

Robert Coombs described antiglobulin testing in 1945.

26/05/24 23

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

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

26/05/24 HISTORY 24

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.
 26/05/24 HISTORY 25

Lewisohn’s Method of Transfusion

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

transfused.
26/05/24 26

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.
 27

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.
1943 It was adopted by the Army in 1945.
(1:4 solution:blood ratio)
26/05/24 28

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.
26/05/24 29

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 States 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 of blood collected in the US in 1992.

26/05/24 30

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.
26/05/24 31

Plastic Blood Bags and Component Separation

26/05/24 32

Component Therapy

Every unit of blood can treat more people.

Revolutionized the treatment of Hemophilia A.

26/05/24 BIBLICAL 33

Changes over Time

In 1943, Beeson described post-transfusion 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.
May 26, 2024 34

Anticoagulant - Preservative Solutions

• To prevent clotting and then to provide nutrients to
maintain red cell viability and functionality during
storage.
• Composition of anticoagulant-preservative:
• - Sodium citrate is a calcium-chelating (binding) agent
that interferes with the calcium-dependent steps in the
clotting cascade and prevents coagulation.
• - Dextrose supports the generation of adenosine
triphosphate (ATP) by glycolysis and in this way
provides nutrients that are required by the red cells.
May 26, 2024 35

Anticoagulant - Preservative Solutions

• - Citric acid is used in conjunction with sodium citrate
and dextrose to make acid citrate dextrose(ACD).

• - Sodium phosphate in CPD/ CPDA -1 maintains pH

and 2,3 DPG (diphosphoglycerate) levels better than
ACD.

• Adenine improves viability of red cells.

 May 26, 2024 36

Anticoagulant - Preservative Solutions

• ACD and CPD are approved anticoagulant preservative solutions
for whole blood and RBC storage at 2 to 6ºC for 21 days
• Because of the lower pH in the ACD preservative, most of the
2,3-DPG is lost early in the first week of storage.
• Therefore, a substitute preservative, CPD, came into widespread
use in the United States in the 1970s because it was superior for
preserving this organic phosphate.
• This effect is the result of a higher pH.
• Even in CPD, RBCs become low in 2,3-DPG by the second week
 May 26, 2024 37

Anticoagulant - Preservative Solutions

• Subsequent studies led to the addition of various chemicals, along
with the currently approved anticoagulant preservative CPD, in an
attempt to stimulate glycolysis so that ATP levels were better
maintained.
• One of the chemicals approved for addition to CPD by the FDA
in August 1978 is adenine. The incorporation of adenine into the
CPD solution(CPDA-1) increases ADP levels, thereby driving
glycolysis toward the synthesis of ATP.
• CPDA-1 contains 0.25 mM of adenine plus 25 percent more
glucose than CPD.
• Adenine-supplemented blood can be stored at 2 to 6ºC for 35
days. The extra glucose was added because of the lengthened
storage period.
 May 26, 2024 38

Anticoagulant - Preservative Solutions

• Stored RBCs do regain the ability to synthesize 2,3-DPG after
transfusion, but levels necessary for optimal hemoglobin oxygen
delivery are not reached immediately.
• Approximately 24 hours are required to restore normal levels of
2,3-DPG after transfusion.
• The 2,3-DPG concentrations after transfusion have been reported
to reach normal levels as early as 6 hours post transfusion in
normal healthy individuals.
May 26, 2024 39

Anticoagulant - Preservative Solutions

• ACD
• CPD
• CPDA
• CPDA 1
• CPDA 2
 May 26, 2024 40

Additive Solutions
• Additive solutions are preserving solutions that are added to
RBCs after removal of the plasma with or without platelets.
• It provides nutrients needed to maintain the RBCs during storage.
• It helps to overcome the problem of high viscosity of RBC
concentrate during transfusion.
• Example – Saline Adenine Glucose Mannitol (SAGM)
• Advantages:
• - Extends storage of RBCs
• - Lowers viscosity of red cell concentrates for ease of transfusion.
• - Maximum amount of fresh plasma is harvested.
May 26, 2024 41

Additive solutions
• PAGGSM: phosphate-adenine-glucose-guanosine-
saline-mannitol;
• PAG3M: phosphate-adenine-glucose-guanosine-
gluconate-mannitol;
• E-Sol: Erythro-Sol;
• AS: additive solution.
 May 26, 2024 42

Composition and Functions of blood

• Blood is a suspension of various types of cells in a highly
complex, aqueous medium known as plasma.
• The volume of blood of an adult is about 5 litres (7.7
% of body mass).
• The pH of blood is 7.3 – 7.4 which means the degree of acidity-
alkalinity is neutral. Acidic fluids have a pH of less than 7.0 and
alkaline fluids have a pH of more than 7.0.
• The specific gravity (SG) of blood is 1.050 – 1.065 indicating that
it is slightly heavier than water which has an SG of 1.000.
• Plasma is approx. 60% of total volume with the blood cells
accounting for 40%.
• About 90% of plasma consists of water.
 May 26, 2024 43

Composition and Functions of blood

• Blood cells are:
• - Red cells or erythrocytes
• - White cells or leucocytes
• - Platelets or thrombocytes
• These cells are suspended in plasma.
• The major function of the red cell cells is:
• - To transport oxygen from the lungs to the tissues for use in
cellular respiration.
• - To remove carbon dioxide from the tissues for excretion via the
lungs during exhalation.
 May 26, 2024 44

Composition and Functions of blood

• The white cells are classified into three major groups:
• - Granulocytes
• - Monocytes
• - Lymphocytes
Functions:
• Responsible for host defence and protecting the body from
infection.
• Granulocytes (Neutrophils, Basophils, Eosinophils):
• Neutrophils – main function is phagocytosis.
• Basophils – capable of phagocytosis and contain histamine.
May 26, 2024 45

Composition and Functions of blood

• Eosinophils – capable of phagocytosis are involved in
allergic responses.

• Platelets or thrombocytes participate in blood coagulation.

• They form a plug to seal damaged blood vessels, thus have

a crucial role in haemostasis or the control of bleeding.
 May 26, 2024 46

Haemostasis
• Haemostasis is a term used to describe the control of bleeding,
formation of a clot, and in the time of healing, the resolution of
the clot and a return to normal.
• The process has 4 major components:
• 1. Vasoconstriction
• 2. Platelet plug
• 3. Clot formation
• 4. Dissolving the clot
• Vasoconstriction: Vascular constriction occurs in a damaged
blood vessel with a mascular wall. This means that the blood
vessel contracts or tightens to minimize further loss of blood.
May 26, 2024 47

Haemostasis
• Platelet plug: When there is an injury, thromboplastin is
released and in the presence of calcium ions, it combines
with prothrombin to thrombin, which in turn activates
platelets.
• Activated platelets amplify the response by activating
more platelets and fibrinogen stimulates their sticking
together as a soft plug that loosely blocks the wound,
dramatically slowing down bleeding.
May 26, 2024 48

Haemostasis
• Clot formation: Each clotting factor has in the meanwhile
been participating in the process, which is why it is called
the coagulation cascade.
• A mesh of insoluble fibrin is finally formed, resulting in a
platelet plug and so reaching the endpoint of the clot
formation.
• As the clot shrinks serum is exuded.

• Dissolving the clot: The last component of the process

is carried out by the enzyme plasmin, which is responsible
for the gradual absorption of the clot by the body, so that
a return to normal is eventually achieved.
 May 26, 2024 49

Clotting factors
• Blood coagulation is the culmination of a series of complex
reactions that bring about a fibrin clot.
• The clotting cascade has two pathways:
• i. the tissue factor pathway
• Ii. The contact activation pathway.
• This is followed by the common pathway, in which clotting
factor X, thrombin and fibrin are activated.
• Clotting factors circulate in the bloodstream in the form of
inactive precursors.
• With the exception of FV, FVIII and platelets, clotting factors
are relatively stable in stored blood.
• FV and FVIII levels in donated blood plasma are stable only
when frozen soon after collection to temperatures below -25ºC
26/05/24 50

Arigato
gozaimashita!
That’s all folks….. Thank you!

Spaciba !

Merci!

MATTHEW 7:7 “ASK, SEEK AND KNOCK….”

ANY QUESTIONS?