Grant: Operating Grant - Priority Announcement: Blood Utilization and Conservation

Platelets play a critical role in the maintenance of hemostasis, and a variety of medical conditions requires transfusion of platelet concentrates (PCs) in order to normalize hemostatic function. The integrity and safety of PCs, however, may be compromised by the presence of pathogens, such as bacteria, viruses and parasites, which prompted the development of pathogen reduction (PR) strategies. Systems for PR of platelets, based on chemically-induced cross-linking and inactivation of nucleic acids, were approved in Europe as early as in 2006 to prevent transfusion transmission of pathogens containing nucleic acids. However, a recent randomized controlled trial (RCT) reported a significant increase in bleeding complications in recipients of pathogen-reduced (versus non-pathogen-reduced) platelets. Here, it is important to consider that PR systems were developed and implemented before platelets were known to contain significant amounts of functionally important nucleic acids, such as mRNAs and mRNA-regulatory microRNAs, which may regulate ~60% of the genes in humans. The effects of PR systems on platelet microRNAs and function may thus explain the increased bleeding observed in recipients of pathogen-reduced platelets, despite the compensatory platelet transfusions given to make up for the cellular losses caused by PR. Therefore, we elaborated this proposal that aims to verify the hypothesis that the deterioration of platelets stored under blood bank conditions is related, at least in part, to an alteration of microRNA/mRNA function, which may be worsened by PR strategies that are being implemented worldwide. Realization of this proposal may (i) bring new knowledge and perspective on the storage of blood platelets and products, (ii) provide key insights into the molecular defects observed in PR-treated platelets, and (iii) lead to significant improvement in stored blood platelets and products management, and have an important impact in transfusion medicine.