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Semin Thromb Hemost 2010; 36(5): 550-557
DOI: 10.1055/s-0030-1255449
© Thieme Medical Publishers

Recombinant Anticoagulant Factors for Adjunctive Treatment of Sepsis

Marcel Levi1 , 2 , Ester Lowenberg1 , 2 , Joost C.  Meijers1 , 3
  • 1Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  • 2Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  • 3Laboratory of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Further Information

Publication History

Publication Date:
14 July 2010 (online)

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ABSTRACT

Inflammation and coagulation play a pivotal role in the pathogenesis of sepsis. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory activity. The intricate relationship between inflammation and coagulation has major consequences for the pathogenesis of microvascular failure and subsequent multiple organ failure, as a result of severe infection and the associated systemic inflammatory response. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Important factors include endothelial-bound anticoagulant mechanisms, such as the antithrombin system, the (activated) protein C/thrombomodulin system, and tissue factor pathway inhibitor, which are all impaired during sepsis. Restoration of these anticoagulant pathways is currently evaluated in several clinical studies. Production of these physiological anticoagulants by recombinant technology greatly facilitates this adjunctive treatment strategy.

KEYWORDS

Sepsis - disseminated intravascular coagulation - antithrombin - activated protein C - thrombomodulin - tissue factor pathway inhibitor

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Marcel LeviM.D. 

Department Internal Medicine, Academic Medical Centre F-4

Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

Email: m.m.levi@amc.uva.nl