title: Antithrombotic effect of a monoclonal antibody against tissue factor in a rabbit model of platelet-mediated arterial thrombosis.
abstract: Activation of the coagulation system by contact of circulating blood with tissue factor, a component of the extrinsic blood coagulation pathway that is produced in the vessel wall, may represent a pathway for the initiation of thrombosis in atherosclerotic vessels. This hypothesis was tested in vivo in a rabbit femoral artery eversion (inside-out) graft model, in which the adventitia, with its tissue factor, was exposed to circulating blood. Intra-arterial infusion of a neutralizing monoclonal antibody against tissue factor (D3) at a rate of 12 mg/kg over 15 minutes prevented thrombosis of a 7-8-mm eversion graft within a 2-hour observation period in four of five rabbits, whereas with a control antibody infusion (MA-15C5), occlusion occurred within 2 hours in five of six rabbits. In vitro immersion before reinsertion of the arterial segment in a solution containing 2 mg/ml of the control antibody for 30 minutes was associated with occlusion in all six rabbits, whereas pretreatment with D3 was associated with persistent patency in three of nine rabbits. Stepwise logistic-regression analysis of the results with perfusion status as the dependent variable and type of antibody (D3 or MA-15C5), application method (infusion versus immersion), and graft segment length as independent variables yielded a significant difference in frequency of occlusion with the two antibodies (p = 0.016). It is concluded that exposure of tissue factor to flowing blood may constitute a trigger mechanism for platelet-mediated arterial thrombosis.
authors.affiliation: Cardiac Unit, Massachusetts General Hospital, Boston 02114.
authors.forename: I K
authors.initials: IK
authors.lastname: Jang
authors.forename: H K
authors.initials: HK
authors.lastname: Gold
authors.forename: R C
authors.initials: RC
authors.lastname: Leinbach
authors.forename: J T
authors.initials: JT
authors.lastname: Fallon
authors.forename: D
authors.initials: D
authors.lastname: Collen
authors.forename: J N
authors.initials: JN
authors.lastname: Wilcox
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001792:Blood Platelets / Q000502:physiology*; D011817:Rabbits; D013925:Thromboplastin / Q000276:immunology / Q000502:physiology*; D013927:Thrombosis / Q000209:etiology / Q000473:pathology / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D013925:Thromboplastin