Cold-stored platelets to reverse dual antiplatelet therapy

Project: Research


  • Moritz Stolla (PI)


Dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitors has improved outcomes in patients with acute coronary syndromes. However, major bleeding complications have compromised the benefits of these drugs and there are currently no drug antidotes. Room temperature-stored platelet (RTP) transfusions can reverse the effect of aspirin, however they are not effective at reversing the effects of P2Y12 inhibitors. Up to three-day 4C cold-stored platelet (CSP) transfusions are approved by the FDA for the management of actively bleeding patients, but CSP transfusions have never been investigated for the reversal of DAPT. CSP may have several advantages over RTP in this setting: 1) CSP are pre-activated and therefore, may be hemostatically superior, 2) our preliminary data show better in vitro aggregation responses to ADP (the agonist blocked by P2Y12 inhibitors), 3) in a previous study the dose of CSP required to reverse the aspirinated bleeding time was only of RTP. Furthermore, CSP have a shortened post-transfusion survival of around one day. This could be an advantage, since it would allow for a short-term targeted reversal in bleeding patients who are simultaneously at risk for coronary thrombosis. We propose to conduct a randomized pilot feasibility study of CSP transfusions versus RTP transfusions in patients receiving DAPT who require drug reversal prior to surgery. We will assess feasibility and gather first data on safety and in vivo efficacy via drainage output, and number of RBC transfusions and in vitro platelet activation tests before, and serially during and after surgery. In summary, there is a clear unmet clinical need for reversal of potent antiplatelet drugs. Our study will be the first to investigate the feasibility, safety, and efficacy of CSP vs. RSP transfusions to reverse DAPT and could have a practice-changing impact.
Award amount$228,690.00
Award date04/01/2019
Program typeCareer Development Award
Award ID19CDA34660281
Effective start/end date04/01/201903/31/2022