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• W1848658613 abstract "Approximately 30 years ago, it was realized that red blood cell (RBC) storage could be extended and viability improved by partial removal of the anticoagulant-preservative and replacement with a RBC crystalloid additive solution (AS).1 In the United States, platelets (PLTs) harvested from whole blood or apheresis donations are currently stored in gas-permeable plastic containers suspended in plasma anticoagulant-preservatives that were originally intended for RBC preservation. Although early investigations in the United States experimented with PLT ASs (PASs),2, 3 more than a decade would pass after the introduction of RBC ASs until European blood centers began to store PLTs in non–glucose-, acetate-based ASs. This trend was accompanied by a manufacturing shift from PLT-rich plasma derived to buffy coat–derived whole blood PLTs, a processing schema that is more amenable to automation. It was quickly realized that such solutions resulted in a decrease in pH after several days of storage4 and it became necessary to ensure adequate plasma retention (35%) to maintain pH. In the United States and Canada, there has been little movement towards PAS until recently, but recognition of some advantages to PAS may well accelerate this trend. Why store PLTs in ASs? The real or potential advantages can be summarized as follows: 1) there is the ability to manipulate the chemical composition of the PAS to optimize viability; 2) removal of plasma may abrogate adverse events attributable to plasma proteins or other molecules in solution, such as transfusion-related acute lung injury (TRALI), ABO-mismatched hemolysis, and allergic reactions; 3) there is a plasma-saving effect that can produce a transfusable product or increase the source plasma supply to fractionators for plasma derivative manufacture; 4) the PAS milieu could be more suitable for application of pathogen reduction technology; and 5) developments in automation in the processing of whole blood donations can be coupled to plasma expression and PAS replacement. These advantages can be separated into “clinical” advantages (enhanced viability and risk reduction by plasma removal) and “manufacturing” advantages; only the clinical advantages will be discussed further in this editorial. PAS can be divided into non–glucose-containing PAS5 and glucose-containing PAS (GC-PAS).6 Because of the difficulties with steam sterilization of glucose at a pH value of greater than 5.8, most PASs in clinical use in Europe are non–glucose-containing PAS and require significant plasma retention as a source of glucose and buffering capacity. Energy metabolism in stored PLTs proceeds through glycolysis and β-oxidation of long-chain fatty acids. Pyruvate generated through glycosis may be reduced to lactic acid or further decarboxylated to acetyl CoA, which is also the end product of β-oxidation and provides an essential fuel for the tricarboxylic acid cycle and oxidative phosphorylation.7 This results in O2 consumption and CO2 generation and, hence, the need for gas-permeable containers and agitation. In non–glucose-containing ASs, the starting concentration of glucose (Day 0) is approximately 5 to 10 mmol per L, which may be insufficient; therefore, sodium acetate (>15 mmol/L) is commonly used as a supplement.8, 9 Sodium acetate supplies a two-carbon substrate for energy metabolism, but also is oxidized to CO2, which generates bicarbonate and, thus, contributes to buffering capacity. Other additions, such as sodium bicarbonate (enhance buffering capacity), phosphate10 (buffer effect and stimulation of glycolysis), magnesium, and potassium11 (activation reduction) improve in vitro functionality and have become incorporated into several proprietary formulations. GC-PASs have also been studied.12-14 This approach allows higher initial glucose concentrations (>20 mmol/L). All such solutions to date also contain sodium acetate (>15 mmol/L) and many of the other chemical ingredients as described above. There is an indication that GC-PASs may maintain pH better beyond Day 513, 14 and, hence, may be preferred to nonglucose PAS if a longer shelf life is required, assuming that the problem of bacterial growth can be overcome. PLT storage under such circumstances retains in vitro functional properties, raising the tantalizing possibility that some day an ideal PLT Shangri-La may be realized! The logistics of steam sterilization of high-glucose-containing solutions require some workarounds, possibly involving two components in separate containers, mixed with the plasma-depleted PLT concentrate immediately before storage. The second clinical advantage for PAS lies in partial plasma removal and, hence, the potential to reduce adverse events attributable to contents in the supernatant. Plasma removal by washing has previously been shown to be effective in reducing transfusion reaction rates15-17 and more recently, the decreased plasma content present in AS-stored PLTs has also shown to be associated with a reduction in transfusion reaction rates.18-20 The relative decrease observed in these reports is of the order of 50 percent (from 5.5% to 2.4%;18 from 12% to 5.3%;19 and from 1% to 0.57%20). In this issue of TRANSFUSION, Azuma and colleagues21 provide clinical experience with M-sol–suspended pheresis PLTs. M-sol is a glucose-containing AS produced by mixing ACD-A, sodium bicarbonate, an acetate ringer solution, and MgSO4, which shows promise as a long-term PLT preservative; the resultant solution is sterilized by microfiltration.14 In this report, 12 patients were studied, each of whom had experienced at least two previous transfusion reactions to leukoreduced apheresis PLTs suspended in plasma, despite prophylactic pretransfusion medication. A total of 113 reactions had occurred in these 12 patients; the vast majority appeared allergic in type (urticaria, vasomotor, respiratory) with only a single report of chills. Two “test” processes were used to replace the plasma: In one schema, ACD-A and M-sol were used before centrifugation, with subsequent plasma expression and resuspension in M-sol. In some cases, centrifugation occurred without the preaddition of ACD-A/M-sol. As much plasma as possible was expressed and residual (carryover) plasma was estimated as less than 10 percent. All modified PLT products were stored for 24 hours and then transfused. A dramatic reduction in reactions was observed from 113 reactions before product modification to a single reaction after modification. This modification resulted in an observed decrease in reaction rates from 42 percent with plasma suspended PLTs to 0.64 percent in the AS-suspended PLTs. Moreover, contrary to previous reports,18, 19 corrected count increments (CCIs) obtained at 1 and 24 hours after transfusion showed CCIs essentially equivalent, if not better, with the M-sol–suspended PLTs. These data are interesting and add supportive clinical data that AS-stored PLTs will abrogate transfusion reactions. Three important aspects of this report merit more attention. The apheresis PLTs had their plasma replaced on Day 2, not on the day of manufacture (Day 0); the PLTs were stored for only 24 hours before transfusion; and the degree of plasma removal (>90%) is much greater than is currently achievable with available PAS. These aspects of the study design may be relevant in explaining the dramatic reduction in observed reactions and may have led to an overestimation of achievable benefits. Nevertheless, this report21 and previous reports,18-20 taken together, are encouraging: it is unclear whether TRALI reactions will be reduced by PAS, but implementation of this approach as a TRALI risk reduction step merits serious consideration. These interesting data add impetus to the move toward the introduction of PAS in the United States." @default.
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• W1848658613 date "2009-02-01" @default.
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• W1848658613 title "Additive solutions for platelets: is it time for North America to go with the flow?" @default.
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