title: Natural anticoagulant inhibitors: activated Protein C.
abstract: Protein C is a vitamin-K-dependent zymogen, whose congenital deficiency state leads to increased risk for venous thrombosis. Activated Protein C (aPC) exerts its anticoagulant function by inhibiting the cofactors in the clotting cascade, Factors Va and VIIIa. In addition, aPC displays anti-inflammatory, anti-apoptotic and profibrinolytic activities. A recombinant form of human aPC (rhAPC) is the first drug reported to improve survival in patients with severe sepsis. The major toxicity associated with treatment is bleeding. Appropriate use of rhAPC depends on an understanding of its mechanisms of action and risk:benefit profile. The goals of this review are: to describe the Protein C pathway; to discuss the definitions, epidemiology and pathophysiology of severe sepsis; to provide a conceptual framework for understanding the role of rhAPC in this syndrome; and to address frequently asked questions about the day-to-day use of this agent.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RW-663, Boston, MA 02215, USA. waird@bidmc.harvard.edu
authors.forename: William C
authors.initials: WC
authors.lastname: Aird
mesh_terms: D000925:Anticoagulants / Q000378:metabolism / Q000627:therapeutic use; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D017410:Practice Guidelines as Topic; D011486:Protein C / Q000378:metabolism / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D000925:Anticoagulants; D011486:Protein C