Characterization of refrigerated platelets to improve storage time and function for transfusion

Platelets are vital for regulating thrombosis and hemostasis. Current blood bank practice dictates platelets are stored at room temperature (RT, 22°C) for no more than 5 days owing to a high risk of bacterial contamination. Refrigeration (4°C) of platelets can mitigate issues of contamination and may even extend shelf life since metabolism is slowed at the lower temperature. However, cold storage of platelets was abolished due to poor recovery and survival upon transfusion. This dissertation demonstrates the feasibility of using cold-stored platelets to improve transfusion efficiency and prolong storage time for the treatment of acute bleeding. Apheresis platelets from healthy donors (n=4-10) were utilized. Platelets were stored at either RT (RT-PLT) or 4°C (4C-PLT) from 5-15 days and characterized in terms of hemostatic function, activation markers, metabolism, safety in response to physiologic inhibitors, and apoptosis status. 4C-PLT showed superior preservation of hemostatic potential, reduced metabolic activity, compared to RT-PLT at Day 5 of storage, but 4C-PLT also exhibited higher levels of activation creating cause of concern for unwanted thrombosis upon transfusion. When treated with endothelial inhibitors 4C-PLT showed similar aggregation, activation, and adhesion profiles as fresh platelets, suggesting 4C-PLT respond to physiologic controls and may truly be safe upon transfusion. Mitochondrial depolarization was increased in 4C-PLT, but caspase activity remained low compared to RT-PLT, suggesting full-fledged apoptosis in RT and only partial initiation of apoptosis in 4°C. Altogether, the data presented in this dissertation strengthens the case to re-evaluate the use of cold-stored platelets for therapeutic transfusion.