This article is part of the supplement: Severe sepsis and drotrecogin alfa (activated)

Review

Recombinant human activated protein C: current insights into its mechanism of action

Marcel Levi¹ and Tom van der Poll^1,2,3

¹Department of Medicine, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands

²Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands

³Center for Experimental and Molecular Medicine, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands

author email corresponding author email

Critical Care 2007, 11(Suppl 5):S3doi:10.1186/cc6154

Published:	19 December 2007

Abstract

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.