title: Recombinant human factor VIIa-induced alterations in tissue factor and thrombomodulin in patients with advanced liver cirrhosis.
abstract: BACKGROUND
  Recombinant human factor VIIa (rhFVIIa) is used to treat hemophilia and occasionally individuals with liver disease. The aim of the present study was to investigate the consequences of rhFVIIa in individuals with advanced liver disease in an attempt to understand the mechanism of action of rhFVIIa in this unique population.
  
  
  METHODS
  Levels of plasma tissue factor, plasminogen activator inhibitor-1, tissue factor pathway inhibitor, fibrin split products, D-dimers and free thrombomodulin were measured following the administration of rhFVIIa in 17 subjects. The results were compared to normal controls.
  
  
  RESULTS
  The prothrombin time declined from 20.2 +/- 2.8 s to 14.3 +/- 3.9 s (P < 0.01). No change in the activated partial thromboplastin time occurred. A 15.6% reduction in thrombomodulin was observed (P < 0.05). A mean 75.2% reduction in plasma tissue factor occurred (P < 0.01). Tissue factor pathway inhibitor levels declined to less than the control value (P < 0.05). No changes in plasminogen activator inhibitor-1, fibrin split products or D-dimer levels occurred.
  
  
  CONCLUSIONS
  These data demonstrate that rhFVIIa administration to individuals with liver disease results in (i) a transient improvement in the prothrombin time; (ii) no change in the activated partial thromboplastin time; and (iii) a marked reduction in the levels of thrombomodulin and tissue factor. These data suggest that rhFVIIa binds tissue factor and enhances tissue factor and thrombomodulin clearance from the circulation.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, Illinois, USA. david.vanthiel@aurora.org
authors.forename: David H
authors.initials: DH
authors.lastname: Van Thiel
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Farr
authors.forename: Ayse L
authors.initials: AL
authors.lastname: Mindikoglu
authors.forename: Akira
authors.initials: A
authors.lastname: Todo
authors.forename: Magdalene M
authors.initials: MM
authors.lastname: George
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005167:Factor VII / Q000627:therapeutic use*; D015942:Factor VIIa; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D018180:Thrombomodulin / Q000097:blood* / Q000187:drug effects; D013925:Thromboplastin / Q000187:drug effects / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D011994:Recombinant Proteins; D018180:Thrombomodulin; D005167:Factor VII; D013925:Thromboplastin; C103587:recombinant FVIIa; D015942:Factor VIIa