Blood Banking Chapter 1 (trans) PDF

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CHAPTER 1Historical Overview 1492 – blood was taken from 3 youngmen and given to the stricken Pope Innocent VII; unfortunately, they all died. Clotting – was the principal obstacle toovercome. 1869 – Braxton Hicks recommendedsodium phosphate. First example of blood preservation research. 1901 – ...

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CHAPTER 1 Historical Overview 

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1492 – blood was taken from 3 young men and given to the stricken Pope Innocent VII; unfortunately, they all died. Clotting – was the principal obstacle to overcome. 1869 – Braxton Hicks recommended sodium phosphate. First example of blood preservation research. 1901 – Karl Landsteiner discovered ABO blood groups; explained the serious reactions that occur in humans as a result of incompatibility; won Nobel prize. Edward E. Lindemann – was first to succeed in making devices designed for performing the transfusions; carried out vein-to-vein transfusion of blood by using multiple syringes and a special cannula for puncturing the vein through skin, but time consuming. Unger – designed his syringe-valve apparatus that transfusions from donor to patient by an unassisted physician became practical. 1914 – unprecedented accomplishment in blood transfusion was achieved; Hustin reported the use of sodium citrate as an anticoagulant sol’n for transfusions. 1915 – Lewisohn determined the minimum amount of citrate needed for anticoagulation; demonstrated its nontoxicity in small amounts. Development of preservative sol’ns to enhance the metabolism of the RBCs. 1916 – glucose was evaluated when Rous and Turner introduced a citratedextrose sol’n for preservation of blood; the function of glucose in RBC metabolism was not understood until

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1930s; the use of glucose in preservative sol’n is delayed. World War II – Dr. Charles Drew pioneered his work on developing techniques in blood transfusion and blood preservation led to the establishment of a widespread system of blood banks. February 1941 – Dr. Drew was appointed director of the first American red cross blood bank at Presbyterian Hospital; his pilot program became the model for the national volunteer blood donor program of the American Red Cross. 1943 – Loutit and Mollison of England introduced the formula for the preservative acid-citrate-dextrose (ACD). July 1947 – landmark publication of the issue of the Journal of Clinical Investigation, devoted to the topic of blood preservation. 1947 – blood banks were established in many major cities of U.S; transfusion became commonplace. 1957 – Gibson introduced an improved preservative sol’n called citratephosphate-dextrose (CPD), less acidic and replaced ACD as the standard preservative used for blood storage.

The Donation Process 

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Step 1: Educational materials – contains info on the risks of infectious diseases transmitted by blood transfusion. Step 2: The donor health history questionnaire – designed to ask questions that protect the health of both donor and the recipient, is given to every donor.

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Step 3: The abbreviated physical examination – includes blood pressure, pulse, and temp readings; hgb or hct level; and inspection of the arms for skin lesions.

RBC Biology and Preservation Three areas of RBC biology are crucial for normal erythrocyte survival and function:

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Normal chem’l composition and structure of the RBC membrane Hgb structure and function 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 

Represents a semipermeable lipid bilayer supported by a mesh-like protein cytoskeleton structure (Fig. 1-1).

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Phospholipids – main lipid components of the membrane; arranged in a bilayer structure comprising the framework in w/c globular proteins traverse and move. Integral membrane proteins – proteins that extend from the outer surface and span the entire membrane to the inner cytoplasmic side of the RBC. Peripheral proteins – a second class of membrane proteins; beneath a lipid bilayer; located and limited to the cytoplasmic surface of the membrane forming he RBC cytoskeleton.

Metabolic Pathways 

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RBCs’ metabolic pathways that produce ATP are mainly anaerobic bec. the function of RBC is to deliver O2, not to consume it. Energy must be generated almost exclusively through the breakdown of glucose bec. the mature erythrocyte has no nucleus and there is no mitochondrial apparatus for oxidative metabolism.

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RBC Preservation 

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Goal – to provide viable and functional blood components for patients requiring blood transfusion. RBC viability – a measure of in vivo RBC survival ff. transfusion. Bec. blood must be stored from the tie of donation until the time of transfusion, the viability of RBCs must be maintained during the storage time as well. U.S. FDA requires an ave. 24-hr posttransfusion RBC survival of more than 75%. FDA mandates that RBC integrity be maintained throughout the shelf-life of the stored RBCs. Assessed as free hgb less than 1% of total hgb.

These two criteria are used to evaluate new preservation sol’ns and storage containers. Post-transfusion RBC survival – to determine it, RBCs are taken from healthy subjects, stored, and then labeled with radioisotopes, reinfused to the original donor, and measured 24 hrs after transfusion. To maintain optimum viability, blood is stored in the liquid state bet. 1degC and 6degC for a specific number of days, as determined by the preservative sol’n(s) used. Storage lesion – correlated to the loss of RBC viability, w/c is associated with various biochemical changes (table 1-2).

Additive Solutions Anticoagulant Preservative Solutions 

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Table 1-3 lists the approved anticoagulant preservative sol’ns for whole blood and RBC storage at 1degC to 6degC. Addition of various chem’ls – along w/ the approved anticoagulant preservative CPD, was incorporated in an attempt to stimulate glycolysis so that ATP levels were better maintained. Adenine – incorporated w/ into the CPD sol’n (CPDA-1) increases ADP levels, thereby driving glycolysis toward the synthesis of ATP. CPDA-1 contains 0.25 mM of adenine plus 25% more glucose than CPD. Adenine-supplemented blood can be stored at 1degC to 6degC for 35 days Other anticoagulants are approved for 21 days. Table 1-4 lists the various chem’ls used in anticoagulant sol’ns and their functions during the storage of RBCs.

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Added to RBCs after removal of the plasma with or without platelets. Reasons for development – removal of the plasma component during the preparation of packed RBCs removed much of the nutrients needed to maintain RBCs during storage. Packed RBCs prepared from whole blood units collected in primary anticoagulant preservative sol’ns can be relatively void of plasma with high hematocrits, w/c causes the units to be more viscous and difficult to infuse. Reduce hematocrit from around 65% to 80% to around 55% to 65% with a vol of approximately 300-400 mL. The ability to pack RBCs to fairly high hematocrits before adding additive sol’n also provides a means to harvest greater amts of plasma with or w/o platelets.

Currently, four additive sol’ns are licensed in the U.S:

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Adsol (AS-1; Fenwal Inc.) Nutricel (AS-3; Haemonetics Corp.) Optisol 9AS-5; Terumo Corp.) SOLX (AS-7; Haemonetics Corp.)

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Satellite bag – where additive sol’n is contained and added to the RBCs after most of the plasma has been expressed. All three additives contain saline, adenine, and glucose. Mannitol – AS-1, AS-5, and AS-7; protects against storage-related hemolysis. Citrate and Phosphate – AS-3; same purpose. All of the additive sol’ns approved for 42 days of storage for packed RBCs.

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RBC Freezing  For autologous units; storage of rare  

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blood types; 10 years from the date of freezing. Involves he addition of a cryoprotective agent to RBC that are less than 6 days old. Glycerol – used most commonly; added to the RBCs slowly with vigorous shaking, thereby enabling the glycerol to permeate the RBCs. Usual storage temp is below -65degC. Two conc. of glycerol have been used to freeze RBCs: ↑ conc. glycerol (40% wt/vol) and a ↓ conc. glycerol (20% wt/vol) in the final conc. of cryopreservative.

RBC Rejuvenation  Process by w/c ATP and 2,3-DPG levels are restored or enhanced by metabolic alterations.

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Currently, FDA-approved rejuvenation sol’n contains phosphate, inosine, and adenine. Rejuvenated RBCs may be prepared up to three days after expiration when stored in CPD, CPDA-1, and AS-1 storage sol’ns. Currently, rejuvenated RBCs must be washed before infusion to remove the inosine (w/c may be toxic) and transfused w/in 24 hrs or frozen for long-term storage.

Hemoglobin-Based Oxygen Carriers  Commercial development focused on

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  RBC Substitutes  Box 1-3 lists the potential benefits of  

artificial oxygen carriers. Table 1-9 outlines the different phases of testing. Current research on blood substitutes is focused on two areas: hemoglobinbased oxygen carriers (HBOCs) and perfluorocarbons (PFCs).

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“oxygen therapeutic” indications to provide immediate oxygenation until medical or surgical interventions could be initiated. HemAssist (BAXTER), Hemopure (HbO₂Therapeutics), and PolyHeme (NORTHFIELD Laboratories) - failed due to safety concern of cardiac issues and mortality. Hemopure(HBOC-201) and PolyHeme – still in phase III clinical trials in the U.S and Europe. Hemopure – was approved for clinical use in South Africa in 2001 to treat adult surgical patients who are anemic, and in Russia for acute anemia. Majority have been discontinued due to complications of cardiac toxicity, gastrointestinal distress, neurotoxicity, renal failure, and increased mortality. Table 1-10 summarizes some of the many HBOCs developed.

Platelet Preservation  With the limit of 5 days of storage for platelet concentrates, approximately 20% to 30% of the platelet inventory is discarded either by the blood supplier or the hospital blood bank.

The Platelet Storage Lesion  Loss of platelet quality during storage.  Platelets are stored at 20degC-24degC Perfluorocarbons  Synthetic hydrocarbon structures in w/c 

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all hydrogen atoms have been replaced w/ fluorine. Because of their small size (about 0.2 µm in dm), they are able to pass through areas of vasoconstriction and deliver oxygen to tissues that are inaccessible to RBCs. Fluosol (Green Cross Corps) – was approved by the FDA in 1989 but was removed from the market in 1994 due to clinical shortcomings and poor sales. Perforan West Ltd – is in clinical use in Russia and Mexico. Oxycyte, Oxygen Biotherapeutics Inc. – currently being investigated as an oxygen therapeutic for treatment of traumatic brain injury in Switzerland and Israel.

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w/ maintaining continuous gentle agitation throughout the storage period of 5 days. Agitation has been shown to facilitate oxygen transfer into the platelet bag and oxygen consumption by the platelets. Maintenance of platelet component pH is associated with the positive role for oxygen. Maintaining pH was determined to be a key parameter for retaining platelet viability in vivo when platelets were stored at 20degC to 24degC. During storage, a varying degree of platelet activation occurs that results in release of some intracellular granules and a decline in ATP and ADP. The reduced oxygen tension (pO2) in the plastic platelet storage container results in an increase in the rate of glycolysis by platelets to compensate for the decrease in ATP regeneration from the oxidative (TCA) metabolism. This increase glucose consumption and causes increase in lactic acid that must be buffered. This results in a fall in pH. During the storage of platelet concentrates (PCs) in plasma, the principal buffer is bicarbonate. When bicarbonate buffers are depleted during platelet concentrate storage, the pH rapidly falls to less than 6.2, w/c associated with a loss of platelet viability. In addition, when pH falls below 6.2, the platelets swell and there is a disk-tosphere transformation in morphology

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that is associated with a loss of membrane integrity. The platelets become irreversibly swollen, aggregate together, or lyse, and when infused, will not circulate or function. This change is irreversible when the pH falls to less than 6.2. During storage of platelet concentrates, the pH will remain stable as long as the production of lactic acid does not exceed the buffering capacity of the plasma or other storage solution. Table 1-14 summarizes platelet changes during storage platelet storage lesion). It should be noted that except for the change in pH, the effect of in vitro changes on post-transfusion platelet survival and function is unknown, and some of the changes may be reversible upon transfusion. Quality-control measurements required by various accreditation organizations for platelet conc. are platelet concentrate vol., platelet count, pH of the unit, and residual leukocyte count if claims of leukoreduction are made. Platelet swirl – no visible aggregation; immediately before distribution to hospitals, a visual inspection is made that often includes an assessment of platelet swirl. The absence of platelet swirling is associated w/ the loss of membrane integrity during storage, resulting in the loss of discoid shape w/ irreversible sphering. Box 1-4 lists of in vitro platelet assays hat have been correlated w/ in vivo survival.

Clinical Use of Platelets  Platelet components – effectively used

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to treat bleeding associated w/ thrombocytopenia, a marked decrease in platelet number, or dysfunctional platelets. The efficacy of the platelet transfusion is usually estimated from the corrected count increment (CCI) of platelets measured after transfusion. CCI is a calculated measure of px. response to platelet transfusion that adjusts for the number of platelets infused and the size of the recipient, based upon body surface area (BSA). CCI = (postcount – precount) x BSA/platelets transfused

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Where postcount and precount are platelet counts (/µL) after and before transfusion. BSA is the px. body surface area (meter²). Platelets transfused is the number of administered platelets (x 10¹¹). The CCI is usually determined 10 to 60mins. after transfusion. The CCI does not evaluate or assess function of the transfused platelets. Platelets are prepared as conc. from whole blood (whole blood-derived

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conc.) and by apheresis (apheresis platelets). Currently, greater than 92% of platelet transfusions are fr. apheresed platelets and about 8% are pools of whole bloodderived platelets (WBD). Platelets still remain the primary means of treating thrombocytopenia even though therapeutic responsiveness varies accdg. to px. status and platelet storage conditions. One unit of whole blood-derived platelet conc. contains ≥5.5 x 10¹° platelets suspended in 40 to 70 mL of plasma. These platelets may be provided as a single unit or as pooled units; pooled units only have a shelf life of 4 hrs. Apheresis platelets contain ≥3.0 x 10¹¹ in one unit w/c is the therapeutic equivalent of 4 to 6 units of whole blood-derived platelets. There are number of containers used for 5-day storage of whole bloodderived (WBD) and apheresis platelets. Box 1-5 lists the factors to be considered when using 5-day plastic storage bags. Additive sol. may be used for storage of apheresis platelets. In U.S, platelets are being stored in a 100% plasma medium, unless a platelet additive sol. is used. Two platelet additive sol. (PAS) are FDA approved, PAS_C (Intersol) and PAS-F (Isoplate), fore the storage of apheresis platelets for 5 days. PAS – designed to reduced 35% w/ both InterSol and Isoplate. One advantage of this approach provides more plasma for fractionation. There are data indicating that optimal additive sol. may improve the quality of platelets during storage, reduce adverse effects associated w/ transfusion of plasma, and promote earlier detection of bacteria.

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Box 1-6 lists the advantages of using a platelet additive sol. for platelet storage.

Platelet testing and Quality Control Monitoring  For component testing, the FDA Guidance docx recommends: 1) Actual platelet yield (vol x platelet count) must be determined after each platelet collection. 2) Wt/vol conversion is necessary to determine the vol of each plt collection. 3) Bacterial contamination testing as specified by the storage container manufacturer.

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Quality Control (QC) – FDA recommends the ff as part of your QC: 1.) “define a plan for nonselectively identifying collections to be tested. This should ensure testing of components collected on each individual automated blood cell separator device, each collection type and each location.” 2.) “define sampling schemes for actual plt yield (including vol determination) and pH, and residual WBC.” (The plt yield of the

collection and designation of single, double, or triple PC should be made prior to performing the residual WBC count QC.) 3.) “test actual plt yield (plt count x vol) and pH at the maximum allowable storage time for the container system used (or representing the dating period).” “In addition, actual plt yield and pH testing may be conducted on one storage container of a double or triple collection.” 4.) “include the residual WBC count for leukocyte-reduced collections, if manufacturing leukocyte-reduced products.” 5.) “describe the criteria for investigation of failures during QC, and have a method to document all calculations and test results.”

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Table 1-15 lists the Performance Criteria for Platelet Concentrate Collections.

transfusion plt counts and expressing the difference based on the number of plts transfused (CCI). Observation of the swirling phenomenon (absence of aggregation) caused by discoid plts when placed in front of a light source has been used to obtain a semiqualitative evaluation of the retention of plt viability properties in stored units. Extent of shape change and the hypotonic shock response in in vitro test appears to provide some indication abt the retention of plt viability ppts. Maintenance of pH during storage at 20degC to 24degC has been associated w/ the retention of post transfusion plt viability and has been the key issue that has been addressed to improve conditions for storage at this temp. Function is defined as the ability of viable plts to respond to vascular damage in promoting hemostasis.

Platelet Storage and Bacterial Contamination  Major concern associated w/ storage of

 Measurement of Viability and Functional Properties of Stored Platelets  Viability – indicates the capacity of   

platelets to circulate after infusion w/o premature removal or destruction. Platelets have a life span of 8 to 10 days after release fr. megakaryocytes. Storage causes a reduction in this parameter, even when pH is maintained. Viability of stored plts is determined by measuring pretransfusion and post-

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plts at 20degC to 24degC is the potential for bacterial growth if the prepared plts contain bacteria bec. of contamination at the phlebotomy site or if the donor has an unrecognized bacterial infection. Environ...