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

ABSTRACT Background Platelets 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. Objective To evaluate the post-transfusion function and predictors of post-transfusion function for platelets stored for the maximum approved storage times (7-day RSP, 14-day CSP) in healthy volunteers on acetylsalicylic acid (ASA). Methods We 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. Results RSP 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. Conclusion We 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)