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Protective effects of activated protein C in sepsis

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Topic:

New vitamin K-dependent proteins

DOI: http://dx.doi.org/10.1160/TH08-03-0159
Issue: 2008: 100/4 (Oct) pp. 517-726
Pages: 582-592

Protective effects of activated protein C in sepsis

Lisa J. Toltl1,3, Laura L. Swystun1,3, Laura Pepler1,3, Patricia C. Liaw2,3

1Department of Medical Sciences, McMaster University, Hamilton, Ontario, Canada; 2Department of Medicine, McMaster University, Hamilton, Ontario, Canada; 3Henderson Research Centre, Hamilton, Ontario, Canada

Keywords

sepsis, acquired coagulation disorders, protein C/S pathway

Summary

Sepsis remains a complex syndrome associated with significant morbidity and mortality. It is now widely accepted that the pathways of inflammation, coagulation, apoptosis, and endothelial permeability are intimately linked in sepsis pathophysiology.The clinical success of activated protein C (APC), a natural anticoagulant, in reducing mortality in patients with severe sepsis has fuelled basic and preclinical research on the protective effects of this molecule. Over the past 15 years, impressive research advances have provided novel insights into the multifunctional activities of APC.APC is now viewed not only as an anticoagulant, but also as a cell signaling molecule that dampens the excessive or insufficiently controlled host response during sepsis. This review attempts to summarize the pleiotropic activities of APC with focus on its ability to inhibit coagulation, inflammation, apoptosis, and endothelial barrier breakdown. A comprehensive PUBMED literature review up to May 2008 was conducted.

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