Van Thiel D H, Anantharaju A, Mindikoglu A L, Shah N, Leone N, Bejna J, Tarasuk G, Todo A, Mobarhan S, George M
Loyola University (Chicago), Stritch School of Medicine, Maywood, IL 60153, USA.
J Viral Hepat. 2003 Jul;10(4):310-7. doi: 10.1046/j.1365-2893.2003.00429.x.
Individuals with chronic hepatitis C (CHC) progress to cirrhosis and hepatic cancer. Individuals with advanced CHC are coagulopathic and can manifest fibrinolysis. The coagulopathy is a consequence of hepatocytic dysfunction. The fibrinolysis represents a response to local endothelial cell injury, and is of a low-grade. Based upon this hypothesis, the effect of the infusion of recombinant human factor VIIa (rh-FVIIa) on endothelial cell inflammatory integrins and measures of endothelial stress were determined in 17 individuals with advanced CHC. Immediately prior to the infusion of rh-FVIIa, the plasma levels of tissue factor (TF), Thrombomodulin (TM), human soluble ICAM-1 (hs-ICAM-1), human soluble VCAM-1 (hs-VCAM-1), human soluble L-Selectin (hs-L-Selectin), the prothrombin time and the activated partial thromboplastin time were determined. The same parameters were assayed at 5, 10, 30, 120, 240 and 360 min after infusion. TF and TM levels were very high at baseline consistent with a vascular endothelial stress response. Similarly hs-ICAM-1, hs-VCAM-1 as well as L-Selectin levels were increased. Thirty minutes after the infusion, a marked reduction in ICAM-1 and VCAM-1 and to a lesser degree L-Selectin levels was observed. This reduction persisted for 360 min. No change in measures of fibrinolysis [plasminogen activator inhibitor-1 (PAI-1), total tissue factor pathway inhibitor (t-TFPI), activated tissue factor pathway inhibitor (TFPIa), d-dimers (DD), FSP and fibrinogen levels] occurred. In addition, no change in plasma Annexin-V was observed. Based upon these data it can be concluded that: (1) rh-FVIIa corrects the coagulopathy seen in advanced CHC; (2) reduces endothelial cell injury and/or stress as evidenced by the TF, TM, hs-ICAM-1 and hs-VCAM-1 levels in plasma; (3) these changes in coagulation occurred without inducing a propagated vascular thrombosis.
慢性丙型肝炎（CHC）患者会发展为肝硬化和肝癌。晚期CHC患者存在凝血功能障碍，并可出现纤维蛋白溶解。凝血功能障碍是肝细胞功能障碍的结果。纤维蛋白溶解是对局部内皮细胞损伤的一种反应，程度较轻。基于这一假设，在17例晚期CHC患者中，测定了重组人凝血因子VIIa（rh-FVIIa）输注对内皮细胞炎性整合素和内皮应激指标的影响。在输注rh-FVIIa之前，测定血浆组织因子（TF）、血栓调节蛋白（TM）、人可溶性细胞间黏附分子-1（hs-ICAM-1）、人可溶性血管细胞黏附分子-1（hs-VCAM-1）、人可溶性L-选择素（hs-L-Selectin）、凝血酶原时间和活化部分凝血活酶时间。在输注后5、10、30、120、240和360分钟测定相同参数。TF和TM水平在基线时非常高，与血管内皮应激反应一致。同样，hs-ICAM-1、hs-VCAM-1以及L-选择素水平也升高。输注后30分钟，观察到ICAM-1和VCAM-1明显降低，L-选择素水平降低程度较小。这种降低持续360分钟。纤维蛋白溶解指标[纤溶酶原激活物抑制剂-1（PAI-1）、总组织因子途径抑制剂（t-TFPI）、活化组织因子途径抑制剂（TFPIa）、D-二聚体（DD）、FSP和纤维蛋白原水平]无变化。此外，血浆膜联蛋白-V未观察到变化。基于这些数据，可以得出以下结论：（1）rh-FVIIa可纠正晚期CHC患者出现的凝血功能障碍；（2）降低内皮细胞损伤和/或应激，血浆中TF、TM、hs-ICAM-1和hs-VCAM-1水平可证明这一点；（3）这些凝血变化未诱发血管内血栓形成。
