Platelet dysfunction reversal with cold-stored vs. room temperature-stored platelet transfusions

Abstract

ABSTRACTBackgroundPlatelets are stored at room temperature for 5-7 days (RSP). Due to frequent and severe shortages, the FDA recently approved up to 14-day cold-stored platelets in plasma (CSP). However, the post-transfusion function of CSP is unknown and it is unclear which donors are best suited to provide either RSP and/or CSP.ObjectiveTo evaluate thepost-transfusionfunction and predictors ofpost-transfusionfunction for platelets stored for the maximum approved storage times (7-day RSP, 14-day CSP) in healthy volunteers on acetylsalicylic acid (ASA).MethodsWe conducted a randomized cross-over study in ten healthy humans. Subjects donated one platelet unit stored at either RT (RSP) or 4 °C (CSP) based on randomization. Before transfusion, subjects ingested ASA to inhibit endogenous platelets. Transfusion recipients were tested for platelet function and lipid mediators. Platelet units were tested for lipid mediators only. A second round with transfusion of the alternative product and an identical testing sequence followed.ResultsRSP reversed platelet inhibition significantly better in αIIbβ3 integrin activation-dependent assays. In contrast, CSP led to significantly more thrombin generation in recipients, which was not dependent on platelet microparticles, but CSP themselves. Lysophosphatidylcholine-O (Lyso-Platelet Activating Factor) species levels predicted the procoagulant capacity of CSP. In contrast, polyunsaturated fatty acid concentration predicted the aggregation response of RSP.ConclusionWe provide the first efficacy data of extended-stored CSP in plasma. Our results suggest that identifying ideal RSP and CSP donors is possible and pave the way for larger studies in the future.Graphical Abstract 1:Overview of CSP function after 14 days of storage (Created with Biorender)