Red Blood Cell and Platelet Preservation: Historical Perspectives and Current Trends Flashcards
First blood transfusion recorded in history
In 1492, blood was taken from three young men and given to the stricken Pope Innocent VII
The first example of blood preservation research.
In 1869, when Braxton Hicks recommended sodium phosphate.
Discovered the ABO blood groups and explained the serious reactions that occur in humans as a result of incompatible transfusions
Karl Landsteiner
Carried out vein-to-vein transfusion of blood by using multiple syringes and a special cannula for puncturing the vein through the skin.
Edward E. Lindemann
Designed his syringe-valve apparatus that transfusions from donor to patient by an unassisted physician
Lester J. Unger
Reported the use of sodium citrate as an anticoagulant solution for transfusions.
Albert Hustin
Determined the minimum amount of citrate needed for anticoagulation and demonstrated its nontoxicity in small amounts.
Richard Lewishon
Introduced a citrate-dextrose solution for the preservation of blood.
Frances Payton Rouse & J.R. Turner
Pioneered on developing techniques in blood transfusion and blood preservation which led to the establishment of a widespread system of blood banks.
Dr. Charles Drew
Introduced the formula for the preservative acid-citrate-dextrose (ACD)
J.F. Loutit & Patrick L. Mollison
Introduced an improved preservative solution called citrate-phosphate-dextrose (CPD)
Gibson
Amount of whole blood in a unit
450 mL ± 10% of blood (1 pint)
Minimum hematocrit level required before blood unit collection
38%
Level of anticoagulant required when collecting 500ml of blood
70ml
The donor’s red blood cells are replaced within
1 to 2 months after donation
A volunteer donor can donate whole blood every
8 weeks
Components of whole blood
Packed RBCs
Buffy coat (WBCs & platelets)
Plasma
A unit of whole blood–prepared RBCs may be stored for
21 to 42 days
Process of collecting specific blood components
Apharesis
Average life span red of blood cell
120 days
Three areas of RBC biology that are crucial for normal erythrocyte survival and function:
- Normal chemical composition and structure of the RBC membrane
- Hemoglobin structure and function
- RBC metabolism
A semipermeable lipid bilayer supported by a mesh-like protein cytoskeleton structure
RBC membrane
The main lipid components of the membrane
Phospholipids
Proteins that extend from the outer surface and span the entire membrane to the inner cytoplasmic side of the RBC
Integral membrane protein
Membrane protein located and limited to the cytoplasmic surface of the membrane forming the RBC cytoskeleton.
Peripheral membrane proteins
The biochemical composition of the RBC membrane
Approximately 52% protein, 40% lipid, and 8% carbohydrate.
How does ATP levels affect RBC deformability?
The loss of ATP leads to a decrease in the phosphorylation of spectrin and, in turn, a loss of membrane deformability
How does membrane calcium levels affect RBC deformability?
An accumulation or increase in deposition of membrane calcium also results in an increased membrane rigidity and loss of pliability
Organ that functions in extravascular sequestration, and removal of aged, damaged, or less deformable RBCs or fragments of their membrane
Spleen
Cells with a reduced surface-to-volume ratio
Spherocytes
Cells with a permanent indentation in the remaining cell membrane
Bite cells
Ability of a normal RBCs to remain flexible, deformable, and permeable
Deformability
It prevent colloid hemolysis and control the volume of the RBCs.
The permeability properties of the RBC membrane and the active RBC cation transport
How does RBC volume and water homeostasis are maintained
By controlling the intracellular concentrations of sodium and potassium
The erythrocyte intracellular-to-extracellular ratios for Na+ and K+
1:12 and 25:1
Cytoplasmic calcium-binding protein, that is speculated to control energy-dependent calcium-ATPase pumps.
Calmodulin
Importance of calmodulin
Prevents excessive intracellular Ca2+ buildup
Why does RBCs mainly use anaerobic metabolic pathways to produce ATP?
Because the function of the RBC is to deliver oxygen, not to consume it
RBC metabolism may be divided into
Anaerobic glycolytic pathway and three ancillary pathways
The three ancillary pathways
Pentose phosphate pathway
Methemoglobin reductase pathway
Luebering-Rapoport shunt
It generates about 90% of the ATP needed by the RBC
Glycolysis
Provides approximately 10% of the ATP needed by the RBC
Pentose phosphate pathway
This pathway permits the accumulation of an important RBC organic phosphate, 2,3-diphosphoglycerate (2,3-DPG)
Luebering-Rapoport shunt
Significance of 2,3-DPG found within RBCs
The amount of 2,3-DPG found within RBCs has a significant effect on the affinity of hemoglobin for oxygen and therefore affects how well RBCs function post-transfusion.
Hemoglobin’s primary function
Gas transport: oxygen delivery to the tissues and carbon dioxide (CO2) excretion
One of the most important controls of hemoglobin affinity for oxygen is the RBC
2,3-DPG
Unloading of oxygen by hemoglobin is accompanied by
Widening of a space between β chains
Binding of 2,3-DPG
Formation of anionic salt bridges between the chains
Lower affinity to oxygen
The resulting conformation of the deoxyhemoglobin molecule is known as
Tense (T) form
Loading of oxygen by hemoglobin is accompanied by
Established salt bridges are broken
β chains are pulled together
Expelling 2,3-DPG
Higher affinity for oxygen
The resulting conformation of the oxyhemoglobin molecule is known as
Relaxed (R) form
The allosteric changes that occur as the hemoglobin loads and unloads oxygen are referred to as the
Respiratory movement
Sigmoid curve relationship between the dissociation and binding of oxygen by hemoglobin is known as
Hemoglobin-oxygen dissociation curve
The dissociation and binding of oxygen by hemoglobin are not directly proportional to the partial pressure of oxygen (pO2) in its environment. True or false?
True
The normal position of the oxygen dissociation curve depends on three different ligands normally found within the RBC:
H+ ions
CO2
Organic phosphates
Plays the most important physiological role in oxygen dissociation curve
2,3-DPG
In the hemoglobin-oxygen dissociation curve, how does shift to the right works?
Shift to the right of the hemoglobin-oxygen dissociation curve alleviates the tissue oxygen deficit. This rightward shift of the curve, mediated by increased levels of 2,3-DPG, decreases hemoglobin’s affinity for the oxygen molecule and increases oxygen delivery to the tissues.
In the hemoglobin-oxygen dissociation curve, how does shift to the left works?
It increases the hemoglobin-oxygen affinity and a decreases oxygen delivery to the tissues.
Multiple transfusions of 2,3-DPG–depleted stored blood can shift the oxygen dissociation curve to the:
Left
The goal of blood preservation
To provide viable and functional blood components for patients requiring blood transfusion.
It is a measure of in vivo RBC survival following transfusion
RBC viability
How to maintain optimum viability of RBC
Blood is stored in the liquid state between 1°C and 6°C for a specific number of days, as determined by the preservative solution(s) used
DPG-depleted RBCs indicate
Impaired capacity to deliver oxygen to the tissues
2,3-DPG levels in stored blood
Decreased
Amount of iron contained in one unit of RBC
Approximately 220 to 250 mg of iron
The purpose of the addition of various chemicals, along with the approved anticoagulant preservative CPD
It was incorporated in an attempt to stimulate glycolysis so that ATP levels were better maintained.
Chemical incorporated into the CPD solution (CPDA-1) that increases ADP levels
Adenine
How does CPDA-1 increases ADP levels
It drives glycolysis toward the synthesis of ATP
Composition of CPDA-1
0.25 mM of adenine plus 25% more glucose than CPD
Storage time of adenine-supplemented blood
35 days
Storage time of blood with Acid citrate-dextrose (formula A)*
21 days
Storage time of blood with Citrate-phosphate dextrose
21 days
Storage time of blood with Citrate-phosphate- double-dextrose
21 days
Anticoagulant Preservative Solutions used for apharesis components
Acid citrate-dextrose (formula A)*
The reported pathophysiological effects of the transfusion of RBCs with low 2,3-DPG levels and increased affinity for oxygen include
An increase in cardiac output, a decrease in mixed venous (pO2) tension, or a combination of these
Blood stored in all CPD preservatives becomes depleted of 2,3-DPG during:
The second week of storage
Required time to restore normal levels of 2,3-DPG after transfusion
Approximately 24 hours
Material used to store blood
Polyvinyl chloride (PVC) plastic bags
Functions of Citrate (sodium citrate/citric acid)
Chelates calcium; prevents clotting
Functions of Monobasic sodium phosphate
Maintains pH during storage; necessary for maintenance of adequate levels of 2,3-DPG.
Function of Dextrose
Substrate for ATP production (cellular energy)
Function of Adenine
Production of ATP (extends shelf-life from 21 to 35 days)
Preserving solutions that are added to the RBCs after removal of the plasma with or without platelets
Additive solutions (AS)
Reason for developing Additive solutions (AS)
Because the removal of the plasma component during the preparation of packed RBCs removed much of the nutrients needed to maintain RBCs during storage
Efficiency of additive solution in reducing hematocrit
Additive solutions reduce hematocrits from around 65% to 80% to around 55% to 65% with a volume of approximately 300 to 400 mL
Additive solutions licensed in the United States
Adsol
Nutricel
Optisol
SOLX
Benefits of RBC Additive Solutions
- Extends the shelf-life of RBCs to 42 days by adding nutrients
- Allows for the harvesting of more plasma and platelets from the unit
- Produces a packed RBC of lower viscosity that is easier to infuse
The additive solution is contained in bag called
Satellite bag
Additive solutions AS1 AS3 AS5 AS7 are approved to store pRBCS for
42 days