The Coagulation Cascade in Sepsis

Author(s): Ling Wang, Julie A. Bastarache, Lorraine B. Ware

Journal Name: Current Pharmaceutical Design

Volume 14 , Issue 19 , 2008

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Intravascular and extravascular fibrin formation are characteristic findings in patients with sepsis, suggesting that the activation of coagulation and the inhibiton of fibrinolysis are important in the pathogenesis of sepsis. Activation of coagulation during sepsis is primarily driven by the tissue factor (TF) pathway, while inhibition of fibrinolysis is primarily due to increases in plasminogen activator inhibitor -1(PAI-1). Downregulation of the anticoagulant Protein C pathway also plays an important role in the modulation of coagulation and inflammation in sepsis. Recent advances in the understanding of pathogenetic mechanisms of coagulation and fibrinolysis in sepsis may have therapeutic implications. Recombinant human activated protein C (rhAPC) is currently the only pharmacologic therapy that has been shown to reduce mortality in adults with severe sepsis, highlighting the importance of coagulation and fibrinolysis as a therapeutic target in sepsis. This review summarizes recent basic and clinical findings with regard to the role of the coagulation cascade in sepsis and explores potential therapeutic targets in the coagulation and fibrinolytic pathways in the management of sepsis.

Keywords: Coagulation, Sepsis, pathogenesis, tissue factor (TF), inflammation, activated protein C, fibrinolysis

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Article Details

Year: 2008
Page: [1860 - 1869]
Pages: 10
DOI: 10.2174/138161208784980581
Price: $65

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