Potential immune consequences of cold-stored platelet transfusion

The rising interest in using cold-stored platelets (CSP) for improving outcomes in patients with active bleeding has led to multiple clinical trials with the goal of determining the in vivo hemostatic efficacy of CSP compared to standard-of-care room temperature-stored platelets. These trials are concentrated predominantly on safety and hemostatic efficacy measurements in response to therapeutic transfusion with CSP, with safety focused on the usual immune-mediated adverse reactions associated with transfusion, such as allergic and alloimmune reactions. However, given the established relationship between thrombosis and inflammation/immune activation as seen in atherosclerosis, autoimmune disease, and infection (to include the recent COVID-19 pandemic), the goal of this review is to highlight additional mechanisms by which CSP may potentiate or dampen immune activity in the context of therapeutic CSP transfusion in actively bleeding patients, thus highlighting areas of future research.