Abstract
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
Current Pharmaceutical Design
Title: The Coagulation Cascade in Sepsis
Volume: 14 Issue: 19
Author(s): Ling Wang, Julie A. Bastarache and Lorraine B. Ware
Affiliation:
Keywords: Coagulation, Sepsis, pathogenesis, tissue factor (TF), inflammation, activated protein C, fibrinolysis
Abstract: 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.
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Cite this article as:
Wang Ling, Bastarache A. Julie and Ware B. Lorraine, The Coagulation Cascade in Sepsis, Current Pharmaceutical Design 2008; 14 (19) . https://dx.doi.org/10.2174/138161208784980581
DOI https://dx.doi.org/10.2174/138161208784980581 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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