Hypoxia/hypoxemia-induced activation of the procoagulant pathways and the pathogenesis of ischemia-associated thrombosis

Although oxygen deprivation has long been associated with triggering of the procoagulant pathway and venous thrombosis, blood hypoxemia and stasis by themselves do not lead to fibrin formation. A pathway is outlined through w hich diminished levels of oxygen activate the transcription factor early gr owth response-1 (Egr-1) leading to de never transcription/translation of ti ssue factor in mononuclear phagocytes and smooth muscle cells, which eventu ates in vascular fibrin deposition. The procoagulant response is magnified by concomitant suppression of fibrinolysis by hypoxia-mediated upregulation of plasminogen activator inhibitor-1. These data add a new facet to the bi ology of thrombosis associated with hypoxemia/stasis and imply that interfe rence with mechanisms causing Egr-1 activation in response to oxygen depriv ation might prevent vascular fibrin deposition occurring in ischemia withou t directly interfering with other pro/anticoagulant pathways.