Procoagulant activity on injured arteries and associated thrombi is mediated primarily by the complex of tissue factor and factor VIIa

Christopher M. Speidel, J. Daryl Thornton, Yuan Yuan Meng, Paul R. Eisenberg, Thomas S. Edgington, Dana R. Abendschein

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Background: Rethrombosis limits the efficacy of coronary thrombolysis and may result from surface-associated thrombin, de-novo prothrombin activation, or both. This study was designed to determine the relative roles of thrombin, factor Xa, and the complex of tissue factor and factor VIIa in the procoagulant activity on injured arteries with evolving thrombi. Methods: Extensive vascular injury and platelet-rich thrombi were induced in the abdominal aorta of 25 anesthetized rabbits by applying anodal current through a transluminal electrode for 3 h. Injured vessel segments were excised and placed in a chamber permitting perfusion over the luminal surface and associated thrombus. Results: Vessel segments perfused with recalcified, citrated human plasma induced marked increases in the concentration of fibrinopeptide A, a marker of thrombin-induced fibrin formation, in the effluent plasma after 10 min (4636 ± 18940% of fibrinopeptide A in the nonperfused plasma, n = 5). Perfusion with plasma depleted of vitamin K- dependent coagulation factors prevented the increase in fibrinopeptide A (122 ± 30%, n = 4), indicating the lack of preformed functional thrombin. Furthermore, appearance of fibrinopeptide A was attenuated by perfusion with plasma containing 0.1 μmol/l recombinant tick anticoagulant peptide, a specific inhibitor of factor Xa (594 ± 3200%, n = 3), and by preincubation of vessel segments with a monoclonal antibody to rabbit tissue factor (438 ± 220%, n = 3). Conclusions: Procoagulant activity on injured vessels and associated thrombi is mediated by factor Xa, a product of the functional initiation of coagulation by factor VIIa associated with tissue factor. Accordingly, inhibition of tissue factor-mediated coagulation may be effective for attenuation of active thrombogenesis on injured vessels and during thrombolysis.

Original languageEnglish
Pages (from-to)57-62
Number of pages6
JournalCoronary Artery Disease
Volume7
Issue number1
StatePublished - Jun 19 1996

Keywords

  • coagulation
  • thrombin
  • thrombolysis
  • tissue factor

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