Background: Recent studies have shown that acute traumatic coagulopathy is associated with hypoperfusion, increased plasma levels of soluble thrombomodulin, and decreased levels of protein C but with no change in factor VII activity. These findings led to the hypothesis that acute traumatic coagulopathy is primarily due to systemic anticoagulation, by activated protein C, rather than decreases in serine protease activity. This study was designed to examine the effect of hypoperfusion secondary to traumatic injury on the activity of coagulation factors. Methods: Post hoc analysis of prospectively collected data on severely injured adult trauma patients presenting to a single trauma center within 120 minutes of injury. Venous blood was analyzed for activity of factors II, V, VII, VIII, IX, X, and XI. Base deficit from arterial blood samples was used as a marker of hypoperfusion. Results: Seventy-one patients were identified. The activity of factors II, V, VII, IX, X, and XI correlated negatively with base deficit, and after stratification into three groups, based on the severity of hypoperfusion, a statistically significant dose-related reduction in the activity of factors II, VII, IX, X, and XI was observed. Hypoperfusion is also associated with marked reductions in factor V activity levels, but these appear to be relatively independent of the degree of hypoperfusion. The activity of factor VIII did not correlate with base deficit. Conclusions: Hypoperfusion in trauma patients is associated with a moderate, dose-dependent reduction in the activity of coagulation factors II, VII, IX, X, and XI, and a more marked reduction in factor V activity, which is relatively independent of the severity of shock. These findings suggest that the mechanisms underlying decreased factor V activity-which could be due to activated protein C mediated cleavage, thus providing a possible link between the proposed thrombomodulin/thrombin-APC pathway and the serine proteases of the coagulation cascade-and the reductions in factors II, VII, IX, X, and XI may differ. Preservation of coagulation factor activity in the majority of normally and moderately hypoperfused patients suggests that aggressive administration of plasma is probably only indicated in severely hypoperfused patients. Markers of hypoperfusion, such as base deficit, might be better and more readily available predictors of who require coagulation support than international normalized ratio or activated partial thromboplastin time. Copyright © 2011 by Lippincott Williams & Wilkins.