Safety and Efficacy of 14-Day Cold Stored Platelets in Reversing Effects of Aspirin
Authors: Li Valery J , Bailey Shawn Lawrence , Bawcom-Randall Morgan , Byrne Daire , Miles Jeffrey , Corson Jill , Stolla Moritz 
Published: November 2021

Abstract
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 well-tolerated by all subjects. Storage of platelets in the cold led to a non-significant trend for decreased platelet count, and the total platelet yield at the end of storage was significantly less in 14-day CSP compared to 7-day RSP (p=0.02). However, the corrected count increment did not differ significantly at 1-hr after transfusion. Platelet aggregation using the agonists, arachidonic acid 0.5mM and collagen 2.5ug/mL, did not reveal any significant difference between the two groups at any time points. The primary endpoint, platelet function testing by VerifyNOW, showed a larger change in platelet responsiveness at 1-hr post-transfusion in RSP than in CSP (p=0.03). Surprisingly, only RSP transfusion resulted in a significant change from the pre-transfusion VerifyNow measurements. Later time points showed a slight trend for improved platelet function as measured by VerifyNow with transfusion of both platelet products, but none were statistically significant.
Conclusion: We report the first safety and efficacy data for 14-day cold stored platelets in in healthy humans. While prior in-vitro studies have demonstrated possible hemostatic superiority of cold stored over room temperature stored platelets, we observed inferior reversal of aspirin at early time points with CSP. This was in contrast to the results from our previous study, where 5 day-stored CSP were equivalent to RSP at early post transfusion time points. Further studies are needed to evaluate the maximal storage that provides functional equivalency between CSP and RSP. In addition, studies in actively bleeding patients are needed.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.