Bleeding (hemorrhage) after trauma remains a leading cause of death. Traumatic hemorrhage (TH) causes early innate immune response and clotting disorders. An inappropriate innate immune response after TH leads to an abnormal release of inflammatory mediators that contribute to early inflammation-mediated multi-organ failure (MOF) and death. Complement cascade (ComC) as a first line defense and a master alarm system of the innate immunity, represents a key mechanism to prime overzealous cytokine storm and thromboinflammation that contribute to multi-system inflammatory syndrome (MSIS)-mediated MOF after TH. The purpose of this study is to develop and validate anti-ComC therapies aimed at mitigating the MSIS-induced MOF and increasing survival, thereby improving outcomes during prolonged field care and/or prehospital scenario for TH patients.