Prevention of occlusive coronary artery thrombosis by a murine monoclonal antibody to porcine von Willebrand factor.
A murine monoclonal antibody (mAb) against porcine von Willebrand factor (vWF) induced an antithrombotic state in normal pigs. Thrombosis was induced by a standard procedure of stenosis and mechanical injury of the artery. The mAb was an IgG1 kappa that inhibited vWF-induced platelet aggregation at a titer of 1:6250 and bound to immobilized vWF at a maximal dilution of 1:512,000. The antibody did not affect two other vWF functions, platelet adhesion and binding of coagulant factor VIII (factor VIII:C). The antithrombotic state was characterized by a prolonged bleeding time and lack of plasma vWF activity, but with near-normal levels of factor VIII:C and von Willebrand antigen. The circulating Ag.mAb complex demonstrated a multimeric distribution comparable to that of native plasma vWF. Three groups of pigs were studied: group A consisted of nine untreated animals, eight of which developed occlusive coronary thrombosis; group B, four treated animals with a long bleeding time, none of which developed occlusive thrombosis; and group C, two animals with preexisting thrombosis treated with mAb, in which stable blood flow was reestablished. Morphologically, the group B animals showed adherent platelets covering the injured intima but no thrombosis. This mAb is an antithrombotic agent that prevents platelet thrombosis without affecting intrinsic platelet function.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001760:Bleeding Time; D003326:Coronary Circulation; D003327:Coronary Disease / Q000517:prevention & control*; D003328:Coronary Thrombosis / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000627:therapeutic use; D007145:Immunoglobulin kappa-Chains / Q000627:therapeutic use; D051379:Mice; D010974:Platelet Aggregation; D013552:Swine; D014841:von Willebrand Factor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D014841:von Willebrand Factor