Blood BANK Chapter 1 - RED Blood CELL AND Platelet Preservation Historical Perspectives & Current Trends PDF

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BLOOD BANK CHAPTER 1 – RED BLOOD CELL AND PLATELET PRESERVATION: HISTORICAL PERSPECTIVES & CURRENT TRENDS – HARMENING

BLOOD TRANSFUSION •

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1942 o Pope Innocent VII o While in a semi-comatose state, he received blood from 3 young boys (who all died) o First time a blood transfusion was recorded in history 1615 o Andreas Libavius o Proposed blood transfusion: taking arterial blood from a young man and infusing into the artery of an old man 1628 o William Harvey o Described the blood circulation in the body 1666 o Richard Lower o First successful animal to animal transfusion using dogs o Also performed sheep to man (Arthur Coga) transfusion – 1667 1667 o Jean-Baptiste Denis o First documented animal to man transfusion o Successfully transfused sheep blood into a 15-year-old with long-standing fever o Transfused calf blood into Antoine Mauroy who has a mental illness ✓ Developed transfusion reaction on second attempt ✓ Died few months later due to arsenic poisoning 1668 o Transfusion experiments were banned unless approved by the Faculty of Medicine in Paris Approximately 150 years of dormancy in the study of the physiology of circulation 1818 o James Blundell (obstetrician) ✓ First human to human transfusion ✓ For treating postpartum hemorrhage

ABO BLOOD GROUP SYSTEM •

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1901 o Karl Landsteiner o Discovered the A, B, C (O) blood groups ✓ No available AB patients 1902 o Decastello and Sturli o Discovered AB blood group 1907 o Jan Jansky o Nomenclature ✓ I – O, II – A, III – B, IV – AB 1928

American Association of Immunologists adopted ABO nomenclature 1907 o Ludvig Hektoen o Select donors by blood group and crossmatching o

HISTORICAL OVERVIEW •

RH BLOOD GROUP SYSTEM •

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1939 o Philip Levine o Case Report: Type O woman received blood from Type O husband but with HTR 1940 o Karl Landsteiner & Alex Wiener o Antibodies from immunization of rabbits and guinea pigs with blood of rhesus monkeys caused RBC agglutination of 85% humans tested ✓ Anti-Rh antibodies caused the reaction o Levine was able to show anti-Rh antibodies are responsible for the HTR but was later disproved 1944 o Ronald Fisher o D, C, c, E, e nomenclature of Rh blood group system ✓ Rh system is composed of numerous alleles

BLOOD COAGULATION, PRESERVATION & STORAGE •

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1869 o John Braxton Hicks o Used Na phosphate solution as anticoagulant 1914 o Albert Hustin o Reported first human transfusion with citrated blood ✓ Calcium chelator 1915 o Richard Lewisohn o Proved 0.2% Na citrate is an effective anticoagulant o Determined the minimum amount of citrate needed as anticoagulant ✓ Proper ratio of anticoagulant: blood 1916 o Rous and Turner o Developed citrate-dextrose/ glucose solution 1943 o Loutit and Mollison o Developed acid citrate dextrose (ACD) solution o Blood can be stored for up to 3-4 weeks 1957 o Gibson o Developed citrate phosphate dextrose (CPD) solution

BLOOD BANK CHAPTER 1 – RED BLOOD CELL AND PLATELET PRESERVATION: HISTORICAL PERSPECTIVES & CURRENT TRENDS – HARMENING o

Up to 28 days storage with better RBC survival than ACD

CURRENT STATUS • • • • •

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Amount of whole blood in a unit was 450 mL ±10% blood Now, 500 mL ±10% blood is being collected Units are collected from donors with minimum hematocrit of 38% Total blood volume of most adults is 10-12 pints Units of whole blood collected can be separated into 3 components: o Packed RBCs o Platelets o Plasma Less whole blood has been used to prepare platelets because of increased utilization of apheresis platelets Plasma can be converted by cryoprecipitation to a clotting factor concentrate that is rich in fibrinogen

RBC BIOLOGY AND PRESERVATION •

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Three areas of RBC biology are crucial for normal erythrocyte survival and function: o Normal chemical composition and structure of the RBC membrane o Hemoglobin structure and function o RBC metabolism Defects in any or all of these areas will result in RBCs surviving fewer than the normal 120 days in circulation

RBC MEMBRANE • •

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Represents a semipermeable lipid bilayer supported by a mesh-like protein cytoskeleton structure Phospholipids, main lipid components of membrane, are arranged in a bilayer structure comprising the framework in which globular proteins transverse and move RBC are termed integral membrane proteins Beneath lipid bilayer, a second class of membrane proteins, peripheral proteins, is located and limited to the cytoplasmic surface of membrane forming RBC cytoskeleton

BLOOD BANK CHAPTER 1 – RED BLOOD CELL AND PLATELET PRESERVATION: HISTORICAL PERSPECTIVES & CURRENT TRENDS – HARMENING

DEFORMABILITY • • •

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Normal RBCs must remain flexible, deformable and permeable Loss of ATP leads to a decrease in phosphorylation of spectrin and loss of membrane deformability Accumulation or increase in deposition of membrane calcium also results, causing increase in membrane rigidity and loss of pliability o Marked disadvantage when they pass through small sinusoidal orifices of the spleen Loss of RBC membrane is exemplified by formation of spherocytes and bite cells

PERMEABILITY •

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Permeability properties and active RBC cation transport prevent colloid hemolysis and control the volume of RBCs Abnormality may decrease RBC survival RBC membrane is freely permeable to water and anions Chloride and bicarbonate can transverse the membrane in less than a second The massive exchange of ions occurs through a large number of exchange channels located in RBC membrane RBC membrane is impermeable to cations (Na and K) When RBCs are ATP-depleted, Ca and Na are allowed to accumulate intracellularly and K and water are lost, resulting in dehydrated rigid cell that is subsequently sequestered by the spleen, resulting in a decrease in RBC survival

ANTICOAGULANT PRESERVATIVE SOLUTIONS •

The addition of carious chemicals, along with the approved anticoagulant preservative CPD, was incorporated in an attempt to stimulate glycolysis so that ATP levels were better maintained o Adenine is incorporated into the CPD solution (CPDA-1) which increases ADP levels, thereby driving glycolysis toward the synthesis of ATP

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Preserving solutions that are added to the RBCs after removal of plasma with or without platelets Additive solutions are now widely used One of the reasons for their development is that removal of plasma component during preparation of packed RBCs removed much of the nutrients needed to maintain RBCs during storage

METABOLIC PATHWAYS •

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Pathways that produce ATP are mainly anaerobic because the function of RBC is to deliver oxygen, not consume it Mature erythrocytes have no nucleus, and no mitochondrial apparatus for oxidative metabolism, energy must be generated almost exclusively through the breakdown of glucose

RBC PRESERVATION •

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Goal of blood preservation is to provide viable and functional blood components for patients requiring blood transfusion RBC viability is a measure of in vivo RBC survival following transfusion To determine post-transfusion RBC survival, RBCs are taken from healthy subjects, stored, and then labeled with radioisotopes, reinfused to original donor and measured 24 hours after transfusion To maintain optimum viability, blood is stored in the liquid state between 1°C and 6 °C

ADDITIVE SOLUTIONS

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BLOOD BANK CHAPTER 1 – RED BLOOD CELL AND PLATELET PRESERVATION: HISTORICAL PERSPECTIVES & CURRENT TRENDS – HARMENING •

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Packed RBCs prepared from whole blood units collected in primary anticoagulant preservative solutions can be relatively void of plasma with high hematocrits, which causes the units to be more viscous and difficult to infuse, especially in emergency situations Additive solutions reduce hematocrits from 65%-80% to 55%-65% with a volume of approximately 300-400 mL Additive solution is contained in a satellite bag o Added to the RBCs after most of the plasma has been expressed All 3 additives contain saline, adenine, and glucose AS-1, AS-5 and AS-7 contain mannitol o Protects against storage-related hemolysis AS-3 contains citrate and phosphate

Benefits of RBC Additive Solutions: o Extends shelf-life of RBCs to 42 days by adding nutrients o Allows for the harvesting of more plasma and platelets from the unit o Produces a packed RBC of lower viscosity that is easier to infuse

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RBC REJUVENATION • •

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FREEZING AND REJUVENATION

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RBC FREEZING Primarily used for autologous units and storage of rare blood types • Autologous transfusion o Allows individuals to donate blood for their own use to meet their needs for blood transfusion Procedure for freezing a unit of packed RBC o Addition of a cryoprotective agent to RBCs that are less than 6 days old o Glycerol is used most commonly and added to the RBCs slowly with vigorous shaking, to enable glycerol to permeate the RBCs

Cells are then rapidly frozen and stored in freezer Usual temperature: below -65°C Two concentrations of glycerol have been used to freeze RBCs o High-concentration glycerol (40% weight in volume) o Low-concentration glycerol (20% wt/vol) Most blood banks that freeze RBCs use the high-concentration glycerol technique Frozen RBCs may be stored up to 10 years before thawing and transfusion Once thawed, RBCs demonstrate function and viability near those of fresh blood o

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Process by which ATP and 2,3-DPG levels are restored or enhanced by metabolic alterations FDA-approved rejuvenation solution contains: o Phosphate o Inosine o Adenine Rejuvenated RBCs may be prepared up to three days after expiration when stored in CPD, CPDA-1 and AS-1 storage solution Rejuvenated RBCs must be washed before infusion to remove inosine and transfused within 24 hours or frozen for long-term storage o Inosine may be toxic Rejuvenation process is expensive and time consuming

CURRENT TRENDS IN RBC PRESERVATION RESEARCH IMPROVED ADDITIVE SOLUTIONS •

Research is being conducted to develop improved additive solutions for RBC preservation

BLOOD BANK CHAPTER 1 – RED BLOOD CELL AND PLATELET PRESERVATION: HISTORICAL PERSPECTIVES & CURRENT TRENDS – HARMENING •

Longer storage periods could improve the logistics of providing RBCs for clinical use

PROCEDURES TO REDUCE AND INACTIVATE PATHOGENS •

Develop procedures that would reduce the level of or inactivate residual viruses, bacteria, and parasites in RBC units

FORMATION OF O TYPE RBCS •

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Inadequate supply of O type RBC units that is periodically encountered can hinder blood centers and hospital blood banks in providing RBCs for specific patients Research on how A and B type RBCs can be converted to O type RBCs

BLOOD PHARMING • • • •

Creating RBCs in the laboratory Has the potential to increase the amount of blood available for transfusion Turn HSCs from umbilical cords into Type O, Rh-negative RBCs Not proven practical for routine transfusion

RBC SUBSTITUTES HEMOGLOBIN-BASED OXYGEN CARRIERS • HBOC commercial development focused on “oxygen therapeutic” indications to provide immediate oxygenation until medical or surgical interventions could be initiated

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PERFLUOROCARBONS Synthetic hydrocarbon structures in which all hydrogen atoms have been replaced with fluorine Chemically inert, excellent gas solvents and carry O2 and CO2 by dissolving them Able to pass through areas of vasoconstriction and deliver oxygen to tissues that are inaccessible to RBCs

PLATELET PRESERVATION •

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Platelets are involved in the blood coagulation process and are given to treat or prevent bleeding Given either therapeutically to stop bleeding or prophylactically to prevent bleeding

BLOOD BANK CHAPTER 1 – RED BLOOD CELL AND PLATELET PRESERVATION: HISTORICAL PERSPECTIVES & CURRENT TRENDS – HARMENING •

increment of platelets measured after transfusion o Calculated measure of patient response to platelet transfusion that adjusts for the number of platelets infused and the size of recipient, based on body surface area

Increasing storage time during platelet preservation is one way to reduce the number of outdated platelet units

PLATELET STORAGE LESION •

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Platelet storage still presents one of the major challenges to the blood bank due to its limitation of storing platelets Platelets are stored at 20°C to 24°C with maintaining continuous gentle agitation throughout the storage period of 5 days Agitations had been shown to facilitate oxygen transfer into the platelet bag and oxygen consumption by the platelets Maintaining pH was determined to be a key parameter for retaining platelet viability in vivo when platelets were stored at 20°C to 24°C Platelet storage lesion o Loss of platelet quality during storage o A varying degree of platelet activation occurs that results in release of some intracellular granules and a decline in ATP & ADP

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CLINICAL USE OF PLATELETS •

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Platelet components are effectively used to treat bleeding associated with thrombocytopenia o Marked decrease in platelet number Platelets are transfused when there is quantitative or qualitative defect with the patient’s platelets Efficacy of platelet transfusion is usually estimated from the corrected count

Usually determined 10-60 minutes after transfusion o Does not evaluate or assess function of transfused platelets One unit of WB-derived platelet concentrate contains ≥5.5x10 10 platelets suspended in 4070 mL of plasma o May be provided as single unit or as pooled units o Pooled units only have a shelf life of 4 hours Apheresis platelets contain ≥3.0x10 11 in one unit which is the therapeutic equivalent of 4-6 units of WB-derived platelets

Additive solutions may be used for storage of apheresis platelets Two platelet additive solutions for storage for 5 days o PAS-C o PAS-F PASs are designed to support platelets during storage in reduced amounts of residual plasma Provides more plasma for fractionation

BLOOD BANK CHAPTER 1 – RED BLOOD CELL AND PLATELET PRESERVATION: HISTORICAL PERSPECTIVES & CURRENT TRENDS – HARMENING

PLATELET TESTING AND QUALITY CONTROL MONITORING

PLATELET STORAGE AND BACTERIAL CONTAMINATION •

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Major concern is the potential for bacterial growth if the prepared platelets contain bacteria because of contamination at phlebotomy site or if donor has an unrecognized bacterial infection Room temperature storage and presence of oxygen provide a good environment for bacterial proliferation Sepsis due to contaminated platelets → most common infectious complication of transfusion

PATHOGEN REDUCTION FOR PLATELETS •

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Pathogen inactivation (PI) o Process of treating the blood component, and the components themselves are referred to as being pathogen reduced (PR) PR/PI o Potentially add an additional level of safety by protecting against unknown and newly emerging pathogens

BLOOD BANK CHAPTER 1 – RED BLOOD CELL AND PLATELET PRESERVATION: HISTORICAL PERSPECTIVES & CURRENT TRENDS – HARMENING...