Platelet storage for transfusion in synthetic media: further optimization of ingredients and definition of their roles.
Currently, most platelet concentrates (PC) are stored for transfusion at 20 degrees C to 24 degrees C in autologous plasma. There are potential advantages in replacing some of this plasma with a synthetic medium. In this study, our major goals were to define the optimal ingredients and their concentrations in such a medium and to gain insight into the mechanism by which each ingredient confers benefit. In addition, we wished to validate a new polyvinyl chloride container plasticized with di-n-decyl phthalate (DnDP) for PC storage. PC derived from donations of whole blood were stored for 7 days in autologous plasma or a basic synthetic medium (BSM) containing 15 mmol/L glucose, 21 mmol/L citrate, and physiologic concentrations of salts other than bicarbonate within either the DnDP container or a licensed polyolefin container, PL-732. Metabolic events were characterized and a panel of in vitro tests were used to monitor platelet quality as systematic changes in the BSM were made. Platelet quality was as least as good, if not better, after storage in DnDP in comparison to PL-732. pH consistently decreased to less than 6.0 because of inadequate buffering of lactic acid in BSM alone. However, pH and the in vitro tests were well maintained by either the serial addition of bicarbonate (BSM + B) or the addition of at least 15 mmol/L acetate and 10 mmol/L phosphate (BSM + AP). The benefits of BSM + AP were traced to a decrease in lactic acid production by 33% and 19% relative to plasma and BSM + B, respectively, and the vigorous oxidation of acetate (0.66 +/- 0.09 mmol/d/10(12 platelets). The rates of lactate production and acetate consumption were similar and the pH during storage correlated with difference between the two rates, suggesting that acetate oxidation has an alkalinizing effect equivalent on a molar basis to the acidifying effect of production of lactate and a hydrogen ion. When pyruvate replaced acetate, it was also metabolized vigorously (0.52 +/- 0.06 mmol/d/10(12) platelets). Its presence suppressed lactic acid production by 44% relative to BSM + B and allowed maintenance of pH and platelet quality similar to what is achieved with acetate. The results strongly suggest that the benefit from acetate (or pyruvate) is derived from its oxidation and the use of a hydrogen ion during that oxidation. For reasons that are not yet clear, the omission of phosphate resulted in pH decrease to less than 6.0 in 3 of 9 PC even with acetate present.(ABSTRACT TRUNCATED AT 400 WORDS)
Murphy
S
S
Cardeza Foundation for Hematologic Research, Philadelphia, PA, USA.
Shimizu
T
T
Miripol
J
J
D000085:Acetates / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001793:Blood Preservation / Q000379:methods*; D002470:Cell Survival; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D016895:Culture Media, Serum-Free; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010101:Oxygen Consumption; D010710:Phosphates / Q000494:pharmacology; D010949:Plasma
D000085:Acetates; D002951:Citrates; D016895:Culture Media, Serum-Free; D010710:Phosphates; D019343:Citric Acid; D005947:Glucose