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.
Van Thiel
David H
DH
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, Illinois, USA. david.vanthiel@aurora.org
Farr
Deborah E
DE
Mindikoglu
Ayse L
AL
Todo
Akira
A
George
Magdalene M
MM
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
D015415:Biomarkers; D011994:Recombinant Proteins; D018180:Thrombomodulin; D005167:Factor VII; D013925:Thromboplastin; C103587:recombinant FVIIa; D015942:Factor VIIa