The normal role of Activated Protein C in maintaining homeostasis and its relevance to critical illness

Thrombin is a multifunctional protein, with procoagulant, inflammatory and anticoagulant effects. Binding of thrombin to thrombomodulin results in act ivation of Protein C and initiation of the Activated Protein C anticoagulan t pathway, a process that is augmented by the endothelial cell Protein C re ceptor (EPCR). Activated Protein C has demonstrated antithrombotic, anti-in flammatory, and profibrinolytic properties. Its antithrombotic activity is particularly important in the microcirculation, and Protein C deficiency is associated with microvascular thrombosis. Activated Protein C has also bee n shown to modulate inflammation. When the level of thrombomodulin or Prote in C is reduced in sepsis there is a vicious cycle of coagulation and infla mmation, with potentially lethal consequences. In vitro studies and animal models have shown that Activated Protein C blunts the inflammatory and coag ulant response to sepsis through a variety of mechanisms.