title: Procoagulant activity on injured arteries and associated thrombi is mediated primarily by the complex of tissue factor and factor VIIa.
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 +/- 1894% 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 mumol/l recombinant tick anticoagulant peptide, a specific inhibitor of factor Xa (594 +/- 320%, 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.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Speidel
authors.forename: J D
authors.initials: JD
authors.lastname: Thornton
authors.forename: Y Y
authors.initials: YY
authors.lastname: Meng
authors.forename: P R
authors.initials: PR
authors.lastname: Eisenberg
authors.forename: T S
authors.initials: TS
authors.lastname: Edgington
authors.forename: D R
authors.initials: DR
authors.lastname: Abendschein
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000293:injuries / Q000473:pathology; D001777:Blood Coagulation / Q000502:physiology*; D003328:Coronary Thrombosis / Q000097:blood; D004195:Disease Models, Animal; D015942:Factor VIIa / Q000502:physiology*; D015951:Factor Xa / Q000502:physiology*; D005344:Fibrinopeptide A / Q000502:physiology; D006801:Humans; D008855:Microscopy, Electron, Scanning; D011516:Prothrombin / Q000502:physiology*; D011817:Rabbits; D013917:Thrombin / Q000502:physiology*; D015912:Thrombolytic Therapy; D013925:Thromboplastin / Q000502:physiology*; D013927:Thrombosis / Q000097:blood* / Q000473:pathology
chemical_list: D005344:Fibrinopeptide A; D011516:Prothrombin; D013925:Thromboplastin; D015942:Factor VIIa; D013917:Thrombin; D015951:Factor Xa