[Inhibition of thrombus formation by anti-Willebrand monoclonal antibodies in the guinea pig].

To experimentally evaluate the role of von Willebrand factor in thrombosis, a monoclonal antibody-712-, directed against the binding domain of von Willebrand factor to the platelet glycoprotein Ib and a control antibody D4H1, directed against the light chain of Factor VII C, were injected into guinea pigs. A model of experimental thrombosis induced by laser in guinea pig mesenteric arteries was used. The antibody 712 induced a dose-dependent reduction of the thrombus formation without affecting the bleeding time and the platelet number. Ex vivo, the ristocetin-induced platelet aggregation was inhibited by the antibody 712 in a dose-dependent manner while the adenosine diphosphate-induced platelet aggregation was not modified. In conclusion, this study showed that antibody-712- has a significant antithrombotic activity without inducing a hemorrhagic state, suggesting that the von Willebrand factor--glycoprotein Ib axis was a promising target for the strategy of a new antithrombotic therapy.