Recombinant anticoagulant factors for adjunctive treatment of sepsis

Seminars in Thrombosis and Hemostasis
Marcel LeviJoost C Meijers

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.

Citations

Aug 4, 2011·Seminars in Immunopathology·Katerina OikonomopoulouJohn D Lambris
May 7, 2011·Archives of Pharmacal Research·Dong-Soon Im
Feb 19, 2011·Current Opinion in Infectious Diseases·Tom van der PollMarcel Levi
Nov 14, 2012·Resuscitation·Markus Skrifvars, Ville Pettilä
Jun 19, 2013·Virulence·Willem Joost WiersingaTom van der Poll
Oct 19, 2010·Blood Reviews·Marcel Levi, Joost C Meijers
Aug 21, 2012·Critical Care Medicine·Marcel Levi

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