Recombinant haemostatic protein for therapeutic substitution of platelet function via tripartite haemostatic mechanisms in thrombocytopenic male mice

Platelets play a pivotal role in haemostasis during both external trauma and spontaneous vascular injury. Thrombocytopenia, an abnormally low platelet count caused by conditions such as autoimmune disease or chemotherapy, can lead to excessive bleeding and potentially serious medical complications. Although platelet transfusion remains the most direct and conventional treatment for thrombocytopenia, its clinical use is limited by donor scarcity and safety concerns. In this study, we developed a recombinant Fc-fusion protein composed of fibrinogen-, thrombin-, and collagen-binding modules—representing a tripartite haemostatic mechanism—derived from endogenous proteins or single-chain variable fragments. Intravenous administration of this recombinant protein significantly reduced bleeding in thrombocytopenic male mice subjected to liver laceration by targeting the injury site and promoting fibrin network formation. Importantly, the protein did not induce detectable pulmonary microthrombi and suppressed spontaneous intestinal bleeding in a chemotherapy-induced thrombocytopenic male mouse model. Taken together, these findings suggest that the recombinant protein can recruit fibrinogen and thrombin to collagen-exposed wound sites, facilitating fibrin gel formation even in the absence of platelets. Thus, it may serve as a promising alternative to conventional platelet transfusion therapy in thrombocytopenic conditions. The authors developed a recombinant protein mimicking platelet function by binding to injury sites and forming fibrin networks via thrombin capture. It safely reduced bleeding in trauma and chemotherapy mouse models.