Mechanisms of Coagulation Abnormalities after Trauma Background. Trauma remains the leading cause of death and disability in patients under 40. Coagulopathy is common following trauma and is associated with poor outcome. Our group has identified an Acute Traumatic Coagulopathy, which this grant seeks to characterize. Objective/Hypothesis. Our preliminary human data indicate that there is a close correlation between the development of coagulopathy and the activation of the protein C pathway. Thus, in this work, we are testing the hypothesis that acute traumatic coagulopathy is primarily caused by tissue hypoperfusion resulting in a complement-mediated activation of the protein C pathway. Study Design. In the first objective, a single center, prospective cohort study is examining the timing and causes coagulation derangements after severe trauma and hypoperfusion. The second and third objectives continue to mechanistically define the role of the protein C pathway and complement in the development of these coagulation abnormalities. Relevance. During the first year of this grant we reported that that activation of the anticoagulant protein C is a critical mechanism driving early posttraumatic coagulopathy. Thus, further research into the mechanisms and treatment of coagulation dysfunction after trauma will continue to prevent early and late deaths in severely injured patients.