 In cases of severe sepsis, there is widespread activation of the acute systemic inflammatory response, including activation of the coagulation and complement pathways, as well as endothelial dysfunction.Activated protein C helps regulate the systemic inflammatory response.During sepsis, signalling by the inflammatory cytokines, interleukin-1 and tumour necrosis factor, mediate altered protein transcription in the systemic inflammatory response, resulting in decreased synthesis of the regulatory proteins antithrombin, protein C and protein S, with increased synthesis of prothrombotic proteins Factor VIII, von Willebrand factor, and fibrinogen.