Recombinant Prothrombin Therapy for Hemorrhage

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Uncontrolled bleeding remains one of the leading causes of trauma-induced death. Current treatment recommendations focus on fresh frozen plasma and blood cell transfusions which do not seem to be effective. Over the last few years, these is increasing use of prothrombin complex cencentrate to treat hemorrhage-associated coagulapathy which is effective but induces disseminated intravascular coagulation. Recent animal studies demonstarte that different from prothrombin complex cencentrate, recombinant human prothrombin (factor II) from CHO cells as monotherapy effectively reduced blood loss and improved survival without causing thromboembolism. However, CHO cell is not adequate for cost-effective and functional production. Our preliminary sudies indicate that HEK293 is a highly prefered host that enables high expression level and adequate post-translational modifications. We propose to optimize the production of human recombinant prothrombin from HEK293 cells and compare the efficacy and safety with prothrombin complex concentrate in a porcine model of dilutional coagulapthy.