title: Antithrombotic effect of tissue factor inhibition by inactivated factor VIIa: an ex vivo human study.
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 microg/kg FFR-rFVIIa and 40 to 50 U/kg heparin, group 2 (n=7) received 200 microg/kg FFR-rFVIIa and 100 U/kg heparin, and group 3 (n=8) received 50 microg/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.
authors.affiliation: Cardiology Department, Rabin Medical Center, Petach-Tikva, Israel.
authors.forename: Eli I
authors.initials: EI
authors.lastname: Lev
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Marmur
authors.forename: Milan
authors.initials: M
authors.lastname: Zdravkovic
authors.forename: Julio I
authors.initials: JI
authors.lastname: Osende
authors.forename: Jonathan
authors.initials: J
authors.lastname: Robbins
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Delfin
authors.forename: Merwin
authors.initials: M
authors.lastname: Richard
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Erhardtsen
authors.forename: Mikael S
authors.initials: MS
authors.lastname: Thomsen
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Badimon
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000379:methods; D000818:Animals; D001780:Blood Coagulation Tests / Q000379:methods; D023921:Coronary Stenosis / Q000628:therapy; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D015942:Factor VIIa / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010477:Perfusion / Q000295:instrumentation / Q000379:methods; D010979:Platelet Function Tests / Q000379:methods; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013552:Swine; D013925:Thromboplastin / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: D005343:Fibrinolytic Agents; D011993:Recombinant Fusion Proteins; D005337:Fibrin; D013925:Thromboplastin; D015942:Factor VIIa