Trauma-induced non-compressible hemorrhage is a leading cause of mortality and morbidity in civilian and military settings across multiple age groups. While external compressible hemorrhage can be managed with topical dressings, internal non-compressible wounds are best treated with transfusion or blood products, i.e. red blood cells, plasma, and platelets. Unfortunately, platelets are limited by shelf life, storage, and portability issues, and blood products are subject to donor availability. We have previously developed a synthetic platelet-mimetic nanoparticle that mimics platelet adhesion, aggregation, and procoagulant functions to address the challenges of platelet transfusion. These synthetic platelets can expose phosphatidylserine on their surface upon exposure to plasmin to help colocalize coagulation factors and promote fibrin formation. We evaluated these synthetic platelets in dynamic settings to demonstrate their efficacy in fibrin generation. In conditions that recapitulate trauma-related pathophysiologies, the synthetic platelets increased fibrin generation, showing the potential for these particles in treating hemorrhage.