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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1036.)
© 2002 American Heart Association, Inc.

Thrombosis

Antithrombotic Effect of Tissue Factor Inhibition by Inactivated Factor VIIa

An Ex Vivo Human Study

Eli I. Lev; Jonathan D. Marmur; Milan Zdravkovic; Julio I. Osende; Jonathan Robbins; Jenny A. Delfin; Merwin Richard; Elisabeth Erhardtsen; Mikael S. Thomsen; A. Michael Lincoff; Juan J. Badimon

From the Cardiology Department (E.I.L.), Rabin Medical Center, Petach-Tikva, Israel; The Zena and Michael A. Wiener Cardiovascular Institute (E.I.L., J.D.M., M.R.), Mount Sinai Medical Center, New York, NY; the Cardiovascular Biology Research Laboratory (J.I.O., J.R., J.A.D., J.J.B.), Cardiovascular Institute, Mount Sinai Medical Center, New York, NY; Novo Nordisk A/S (M.Z., E.E., M.S.T.), Copenhagen, Denmark; and the Cleveland Clinic Foundation (A.M.L.), Cleveland, Ohio.

Reprint requests to Dr Juan J. Badimon, Professor of Medicine, Cardiovascular Biology Research Laboratory, Cardiovascular Institute (Box 1030), The Mount Sinai Medical Center, One Gustave L. Levy Pace, New York, NY 10029. E-mail Juan.Badimon{at}mssm.edu

Abstract— FFR-rFVIIa is an inactivated recombinant factor VIIa (rFVIIa) that inhibits the binding of factor VIIa to tissue factor (TF). It has been shown to prevent TF-induced thrombosis in animals. The present study is a substudy of the Active Site Inhibited Seven (ASIS) trial and examines the antithrombotic effect of 3 doses of FFR-rFVIIa in 24 patients undergoing percutaneous coronary intervention (PCI). Group 1 (n=9) received 400 µg/kg FFR-rFVIIa and 40 to 50 U/kg heparin, group 2 (n=7) received 200 µg/kg FFR-rFVIIa and 100 U/kg heparin, and group 3 (n=8) received 50 µg/kg FFR-rFVIIa and 100 U/kg heparin. Blood thrombogenicity was assessed as total thrombus area and fibrin deposition on the perfusion chamber at shear rate conditions typical of mild-moderate coronary stenosis. Baseline blood thrombogenicity was evaluated a day before PCI, after heparin administration. A second perfusion chamber study was performed just before PCI, 15 minutes after the administration of heparin and FFR-rFVIIa. Thrombus formation at a high shear rate was markedly reduced in groups 1 and 2 after drug administration, by 79% to 84% and 76% to 87%, respectively (P<0.004 [group 1], P<0.04 [group 2]). In group 3, moderate thrombus reduction of 46% to 48% was achieved (P<0.04). Fibrin deposition in all 3 groups was nearly eliminated after drug administration. Our data demonstrate that FFR-rFVIIa has a potent antithrombotic effect at different shear rates and severe arterial injury conditions.

Key Words: tissue factor • thrombus formation • factor VIIa • fibrin • platelets