THBD and Sepsis: While overexpression of pro-inflammatory cytokines enhances the activation of clotting cascades in sepsis, there is also good evidence to indicate associated impairment of pathways for essential natural anticoagulant activity, such as the antithrombin system, which is an important inhibitor of thrombin formation and FXa activation; the protein C system including protein S, which is an essential co-factor for the activity of protein C; and for thrombomodulin expression on endothelial cells (reviewed by [28]).