Uncontrolled hemorrhage is the primary cause of potentially preventable death in civilian injuries and combat casualties, and derangements of the coagulation system complicate almost all cases of active bleeding and massive transfusion. These patients die because we do not yet understand the causes of these specific alterations, we cannot accurately and rapidly diagnose them, and we cannot supply targeted therapy quickly enough to effect outcome. Current best practice in trauma care involves the blind provision of large amounts of intravenous blood-derived clotting factor replacement for patients with hemorrhagic shock. Our group and others have recently identified a biochemically distinct acute traumatic coagulopathy that occurs nearly immediately after injury, and is associated with increased morbidity (bleeding, infection, and organ failure), and a nearly 4-fold increase in mortality. Further recent work has identified that this is likely mediated by activation of the protein C system, offering a more complete understanding of the perturbations in coagulation after trauma and the hope of a specific target for therapy. Despite this new insight into acute traumatic coagulopathy, the coagulation milieu after injury remains woefully understudied. Because of this, the Cohen lab has undertaken a multi-faceted, translational investigation of coagulation after trauma and its implications for later immune dysregulation and further morbidity.