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

D. A. Bellinger, T. C. Nichols, M. S. Read, R. L. Reddick, M. A. Lamb, K. M. Brinkhous, B. L. Evatt, T. R. Griggs

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69 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)8100-8104
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume84
Issue number22
DOIs
StatePublished - Nov 1987
Externally publishedYes

ASJC Scopus subject areas

  • General

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