Recombinant human factor VIIa-induced alterations in tissue factor and thrombomodulin in patients with advanced liver cirrhosis

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.