Active site-inactivated factor VIIa prevents thrombosis without increased surgical bleeding: topical and intravenous administration in a rat model of deep arterial injury

Journal of Vascular Surgery
T SöderströmB Arnljots

Abstract

The primary event in the procoagulant response after vascular interventions is the tissue factor (TF)-factor VIIa complex formation, which occurs when TF is exposed to the circulating blood by the inflicted trauma. Human recombinant active site-inhibited coagulation factor VIIa (FFR-rFVIIa) binds well to TF but cannot initiate blood coagulation, and should thereby block thrombus formation. This hypothesis was tested with a rat model of arterial thrombosis. In a blinded randomized study, the antithrombotic and antihemostatic effects of FFR-rFVIIa and heparin were evaluated in a rat model of mechanical deep arterial injury. In one arm of the study, FFR-rFVIIa (0.2 mg in 150 microL) or vehicle alone was applied topically at the site of vascular injury. In the other arm, FFR-rFVIIa (4 mg/kg), heparin (1 mg/kg), or vehicle alone was injected intravenously. FFR-rFVIIa produced a powerful antithrombotic effect after both topical and intravenous administrations (P =.02 and P =.005, respectively) without increasing the surgical bleeding. Heparin prevented thrombosis equally well as FFR-rFVIIa (P =.0007), but doubled the surgical bleeding compared with FFR-rFVIIa (P =.03) and controls (P =.008). In the topical study, the antithrombotic e...Continue Reading

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Citations

Oct 30, 2008·Thrombosis Journal·Karl MalmBjörn Dahlbäck
Oct 28, 2004·Thrombosis Research·Alisa S Wolberg, Robert A S Roubey
Dec 2, 2006·European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery·K Björses, J Holst
Jul 21, 2009·Seminars in Cardiothoracic and Vascular Anesthesia·R Clive Landis
Jul 19, 2002·Seminars in Hematology·Stephan Moll, Harold R Roberts

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