Recombinant human activated protein C: current insights into its mechanism of action.
Impairment of the protein C pathway plays a central role in the pathogenesis of sepsis. Administration of recombinant human activated protein C (rhAPC) may correct the dysregulated anticoagulant mechanism and prevent propagation of thrombin generation and formation of microvascular thrombosis. Furthermore, it may simultaneously modulate the inflammatory response. It is likely that the beneficial effect of rhAPC observed in experimental and clinical studies of severe sepsis results from a combination of mechanisms that modulate the entangled processes of coagulation and inflammation. This review presents an analysis of the various mechanisms of action of rhAPC in sepsis.
Levi
Marcel
M
Department of Medicine, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands. m.m.levi@amc.uva.nl
van der Poll
Tom
T
D000818:Animals; D001778:Blood Coagulation Disorders / Q000188:drug therapy / Q000209:etiology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D011486:Protein C / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism
D005343:Fibrinolytic Agents; D018836:Inflammation Mediators; D011486:Protein C; D011994:Recombinant Proteins; D013917:Thrombin; C421124:drotrecogin alfa activated