Mechanisms of Coagulation Abnormalities and Trauma
Annual rept. 1 Jul 2011-30 Jun 2012
CALIFORNIA UNIV REGENTS SAN FRANCISCO
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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. Purpose 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. Major Findings In the first objective, a single center, prospective cohort study examined the timing and causes coagulation derangements after severe trauma and hypoperfusion. We found an activated protein C mediated coagulopathy after injury and shock. The second and third objectives continue to mechanistically define the role of the protein C pathway and complement in a mouse model in the development of these coagulation abnormalities. Relevance During this grant cycle we identified 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.
- Anatomy and Physiology
- Medicine and Medical Research