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What is immunohematology?

Serologic, genetic, biochemical, and


molecular study of antigens associated with
membrane structures on the cellular
constituents of blood, as well as the
immunologic properties and reactions of
blood component
(Henry, 2011)

Study of blood related antigens and


antibodies as applied to situations in blood
bank and the transfusion service (Whitlock,
2010)
Historical Timeline
1492
Pope Innocent VII
First recorded blood transfusion in
history
1667
Jean Baptiste Denis: first recorded
animal-to-human blood transfusion (calf
blood)
Richard Lower: sheeps blood
1795
Philip Syng Physick: unconfirmed first
human-to-human transfusion
1816
John Henry Leacock: On the
Transfusion of Blood in Extreme Cases
of Hemorrhage
James Blundell: took inspiration from
Leacock in performing transfusions for
women suffering from postpartum
hemorrhages
Late 1800s
Emil Ponfick: RBC lysis in a blood of a
woman who died after sheep blood
transfusion
Leonard Landois: Human RBCs lyse
when mixed in vitro with sera of other
animals
1869
Braxton Hicks: NaPO4 as an
anticoagulant
20th Century
1901: Karl Landsteiner ABO Blood
Group System
1902: Anthony Decastello and Adriano
Sturli AB blood group
20th Century
Edward E. Lindemann: vein-to-vein
transfusion
Unger: syringe-valve apparatus, more
practical
1907
Richard Weil: 1st to perform ABO typing
and began compatibility testing, 1st to
suggest ABO inheritance
Refrigeration of citrated blood prior to
use

1913
Reuben Ottenberg: stressed importance
of compatibility testing
1914
Albert Hustin: sodium citrate as an
anticoagulant solution
1915
Richard Lewisohn: minimum amount of
citrate needed for anticoagulation
1916
Rous and Turner: introduction of citrate
dextrose solution for RBC preservation
1924
Felix Bernstein: proof of inheritance of
blood groups
Issues in race distribution
1927
American Association of Immunologists:
adopted the current ABO terminology
proposed by Landsteiner
1939-1940
Philip Levine (together with Stetson,
Landsteiner and Alex Wiener): 1st
discovery of Rh blood groups
1941
Charles Drew: developing techniques in
blood transfusion and blood
preservation during WWII
1943
Loutit and Mollison: acid-citrate dextrose
formula
1945
Robin Coombs, Rob Race and Arthur
Mourant: (re)discovery of anti-human
globulin (AHG) sera and antiglobulin test
which was first described by Carlo
Moreschi in 1908
1947
Rh immune Globulin for prevention of
Hemolytic Disease of the Fetus and
Newborn
1951
Edwin Cohn: development of cell
separator, paved the way for component
therapy
Carl Walter: blood collection using a
collapsible bag of polyvinyl resin
1957
Gibson: introduction of citratephosphate-dextrose (CPD)
1965
Judith Pool: concentrated factor VIII
found in the cryoprecipitate portion of
plasma
1968
Brinkhous and Shanbrom: pooling of
plasma units to produce factor VIII
concentration
Adverse effects of Transfusion
1970s

Transition to an all-volunteer blood


supply
Availability of commercial testing for
HBV
1980s
The first serologic test to detect HIV was
implemented by blood banks to protect
the blood supply
Opened the possibility of transmission of
blood-borne pathogens other than HBV,
HCV, and HIV through blood transfusion
Non-infectious effects of Transfusion
Transfused leukocytes were found to have a number
of undesirable effects
Graw and colleagues GVHD
prevention by blood component
irradiation
Greenwalt and colleagues first
generation leukocyte filter in the
prevention of febrile transfusion
reactions
Blood Banking in the Modern World
Discovery of West Nile Virus in 2002 as
a new transfusion-transmitted pathogen
Regulation of bacterial contamination on
blood components
Blood substitutes or blood alternatives

Areas of RBC Biology


1. Normal chemical composition and structure
of RBC membrane
2. Hemoglobin structure and function
3. RBC metabolism
RBC Membrane
A semipermeable lipid bilayer supported by a protein
meshlike cytoskeleton structure
1. Phospholipids arranged in bilayer structure
(40%)
2. Proteins integral and peripheral (52%)
3. Carbohydrates 8%
Deformability Factors affecting RBC deformability
1. Loss of ATP levels = decrease in spectrin
phosphorylation
2. Calcium accumulation or increase in
deposition
Permeability

RBC membrane is permeable to water and


anions (Cl- and HCO3-) but impermeable to
cations (Na+ and K+)

To maintain RBC volume and water


homeostasis, intracellular concentrations of
Na+ and K+ are controlled by utilizing ATP
RBC Metabolism

Mainly ANAEROBIC

Glycolysis breakdown of glucose to


generate energy for RBCs

1.
2.
3.
4.

Glycolytic (Embden-Meyerhof) Pathway


Pentose Phosphate Pathway
Methemoglobin Reductase Pathway
Leubering-Rapaport Pathway

Hemoglobin Structure and Function


Hemoglobin Synthesis
1. Adequate iron delivery and supply
2. Adequate synthesis of protoporphyrins
3. Adequate globin synthesis

Types in normal adults


1. HbA (two alpha, two beta chains; 92-95%)
2. HbA2 (two alpha, two delta chains; 2-3%)
3. HbF (two alpha, two gamma chains; 1-2%)
Three functions
1. Transport of O2 from the lungs to tissues
2. Transport of CO2 from tissues to the lungs
3. Buffering of blood

Hemoglobin function
Oxygen delivery to tissues
- 2-3 DPG
- Tense form lower High affinity to
oxygen
- Relaxed form higher High affinity
to oxygen

Loss of RBC viability associated with


various biochemical changes
Decrease in pH, decrease in glucose
consumption, decrease ATP levels,
buildup of lactic acid, loss of RBC
function

Anticoagulant Preservative Solutions


Name
Storage time
Acid-citrate-dextrose (ACD)
21 days
Citrate-phosphate-dextrose (CPD) 21 days
Citrate-phosphate-double dextrose 21 days
Citrate-phosphate-dextrose
-adenine (CPDA-I)
35 days
Hemoglobin-oxygen dissociation curve
Importance: It permits a considerable
amount of oxygen to be delivered to the
tissues with a small drop in oxygen
tension

Additive Solutions
Preserving solutions that are added to
the RBCs after removal of plasma
with/without platelets
Beutler development
Lovric and Hogman implementation
a. Lovric CP2D and additive solution
(saline, adenine, glucose, trisodium
citrate, citric acid, sodium
phosphate)
b. Hogman CPD and additive
solution (saline, adenine, glucose
(SAG), and later with mannitol
(SAGM)

Ligands
1. H+ ions
2. CO2
3. Organic phosphates (2,3 DPG)
Shift to the right
- Increased 2,3 DPG = decrease High
affinity to oxygen = increase oxygen
delivery to tissues

RBC Preservation
RBC viability
Measure of in-vivo RBC survival
following transfusion
75% of cells transfused should remain
viable for 24 hours
Liquid state at 1-6 degrees Celsius for a
specific number of days

RBC freezing
- For autologous units and storage of
rare blood types
- -65 C, 10 years
- Glycerol

Storage lesion

RBC Rejuvenation

Restoration of ATP and 2,3 DPG levels


PIGPA

PIPA
Rejuvesol used to salvage liquidstored RBCs that have reached outdate