[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.
Cissé-Thiam
M
M
Département de Biologie Animale-Faculté des Sciences et Techniques, UCAD Dakar, Sénégal.
Girma
J P
JP
Meyer
D
D
Drouet
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001665:Binding Sites; D005343:Fibrinolytic Agents; D006168:Guinea Pigs; D007834:Lasers; D008638:Mesenteric Arteries; D010974:Platelet Aggregation / Q000187:drug effects; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology; D012310:Ristocetin / Q000494:pharmacology; D013927:Thrombosis / Q000517:prevention & control*; D014841:von Willebrand Factor / Q000276:immunology* / Q000502:physiology
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D012310:Ristocetin