Van Thiel David H, Farr Deborah E, Mindikoglu Ayse L, Todo Akira, George Magdalene M
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, Illinois, USA.
J Gastroenterol Hepatol. 2005 Jun;20(6):882-9. doi: 10.1111/j.1440-1746.2005.03761.x.
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.
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.
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.
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.
重组人凝血因子VIIa（rhFVIIa）用于治疗血友病，偶尔也用于治疗肝病患者。本研究的目的是调查rhFVIIa对晚期肝病患者的影响，以试图了解rhFVIIa在这一特殊人群中的作用机制。
对17名受试者给予rhFVIIa后，检测血浆组织因子、纤溶酶原激活物抑制剂-1、组织因子途径抑制剂、纤维蛋白降解产物、D-二聚体和游离血栓调节蛋白的水平。将结果与正常对照组进行比较。
凝血酶原时间从20.2±2.8秒降至14.3±3.9秒（P<0.01）。活化部分凝血活酶时间无变化。观察到血栓调节蛋白减少了15.6%（P<0.05）。血浆组织因子平均减少75.2%（P<0.01）。组织因子途径抑制剂水平降至低于对照值（P<0.05）。纤溶酶原激活物抑制剂-1、纤维蛋白降解产物或D-二聚体水平无变化。
这些数据表明，对肝病患者给予rhFVIIa会导致：（i）凝血酶原时间短暂改善；（ii）活化部分凝血活酶时间无变化；（iii）血栓调节蛋白和组织因子水平显著降低。这些数据表明，rhFVIIa与组织因子结合，并增强组织因子和血栓调节蛋白从循环中的清除。
