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. 1987 Nov;84(22):8100–8104. doi: 10.1073/pnas.84.22.8100

Prevention of occlusive coronary artery thrombosis by a murine monoclonal antibody to porcine von Willebrand factor.

D A Bellinger 1, T C Nichols 1, M S Read 1, R L Reddick 1, M A Lamb 1, K M Brinkhous 1, B L Evatt 1, T R Griggs 1
PMCID: PMC299486  PMID: 3120185

Abstract

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.

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Selected References

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