Safety and Efficacy of 14-Day Cold Stored Platelets in Reversing Effects of Aspirin

Background: Aspirin is an antiplatelet therapy used to reduce the risk of vascular occlusive events. However, this therapy is associated with an increased risk of bleeding for which there is no antidote currently. Transfusion of 5-day room stored platelets (RSP) at 22°C can reverse the effect of aspirin but surprisingly, the recent randomized PATCH trial showed increased morbidity and mortality for patients who received RSP transfusion for intracranial hemorrhage while on aspirin. Prior studies have shown that cold stored platelets (CSP) at 4°C are mildly activated and may participate in clot formation immediately, thus may have the potential to reduce blood loss more rapidly than RSP in acutely bleeding patients. CSP also have the added advantages of decreased risk of bacterial contamination and longer shelf-life up to 14 days per current FDA variance. However, the function of 14-day CSP in plasma after transfusion is unclear and lacks high quality data. We aimed to evaluate the post-transfusion safety and efficacy of 14-day CSP in reversing the effects of aspirin therapy compared to that of 7-day RSP. Methods: Seven healthy human subjects were included in the analysis of this randomized, controlled, crossover study comparing transfusion of autologous 14-day CSP to 7-day RSP. Each subject participated in two study periods, which crossed over from one storage product to the other (CSP vs. RSP) according to randomization. For each study period, subjects underwent an apheresis platelet collection for autologous transfusion. Platelets were stored for either 14 days for CSP or 7 days for RSP. Subjects received a loading dose of aspirin 24 hours prior to transfusion. Blood was drawn at baseline, immediately pre-transfusion, at 1-hr, 4-hr, and 24-hr post-transfusion for an array of platelet function testing. After a washout period of 10-28 days, second study period commenced with similar sequence of events as the first study period using the other platelet storage product. The primary endpoint is the VerifyNOW Aspirin Reaction Units (ARU) at 1-hr after autologous transfusion. Secondary endpoints include ARU at 4-hr and 24-hr post transfusion, light transmission aggregometry in response to arachidonic acid and collagen, and the corrected count increment. Paired t-tests were used for statistical analysis between the two groups and, where appropriate, the change from pre-transfusion values were analyzed. Results: Transfusion of 14-day CSP and 7-day RSP units were w