Recombinant Anticoagulant Factors for Adjunctive Treatment of Sepsis

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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