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Enhancement of rabbit jugular vein thrombolysis by neutralization of factor xi - in vivo evidence for a role of factor xi as an anti-fibrinolytic factor

Academic Article
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Overview

authors

  • Minnema, M. C.
  • Friederich, P. W.
  • Levi, M.
  • von dem Borne, P. A. K.
  • Mosnier, Laurent
  • Meijers, J. C. M.
  • Biemond, B. J.
  • Hack, C. E.
  • Bouma, B. N.
  • ten Cate, H.

publication date

  • January 1998

journal

  • Journal of Clinical Investigation  Journal

abstract

  • Recent in vitro studies have shown that fibrinolytic activity may be attenuated by a thrombin-activatable fibrinolysis inhibitor (TAFI), which is activated by thrombin, generated via the intrinsic pathway of coagulation in a factor XI-dependent way. Thus factor XI may play a role in the regulation of endogenous fibrinolysis. The aim of this study was to investigate the effect of in vivo inhibition of factor XI and TAFI in an experimental thrombosis model in rabbits. Incorporation of anti-factor XI antibodies in jugular vein thrombi resulted in an almost twofold increase in endogenous thrombolysis compared with a control antibody. A similar effect was observed when the anti-factor XI antibody was administered systemically. Inhibition of TAFI activity also resulted in a twofold increase in clot lysis whereas inhibition of both factor XI and TAFI activity had no additional effect. Thus, we provide the first in vivo evidence for enhanced thrombolysis through inhibition of clotting factor XI, demonstrating a novel role for the intrinsic pathway of coagulation. Furthermore we demonstrate that inhibition of TAFI had a similar effect on thrombolysis. We postulate that inhibition of factor XI activity enhances thrombolysis because of diminished indirect activation of TAFI.

subject areas

  • Animals
  • Antibodies
  • Carboxypeptidase B2
  • Carboxypeptidases
  • Factor XI
  • Fibrinolysis
  • Jugular Veins
  • Neutralization Tests
  • Plant Proteins
  • Rabbits
  • Solanum tuberosum
  • Thrombosis
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Research

keywords

  • TAFI
  • factor XI
  • factor XI deficiency
  • fibrinolysis
  • rabbits
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Identity

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci781

PubMed ID

  • 9421460
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Additional Document Info

start page

  • 10

end page

  • 14

volume

  • 101

issue

  • 1

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