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

  • D A Bellinger
    Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27514.
  • T C Nichols
    Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27514.
  • M S Read
    Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27514.
  • R L Reddick
    Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27514.
  • M A Lamb
    Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27514.
  • K M Brinkhous
    Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27514.
  • B L Evatt
    Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27514.
  • T R Griggs
    Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27514.

書誌事項

公開日
1987-11
DOI
  • 10.1073/pnas.84.22.8100
公開者
Proceedings of the National Academy of Sciences

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説明

<jats:p>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.</jats:p>

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