Ferro D, Basili S, Lattuada A, Mantovani B, Bellomo A, Mannucci P M, Violi F
Institute of Clinical Medicine I, University of Rome La Sapienza, Italy.
Ital J Gastroenterol Hepatol. 1997 Oct;29(5):434-40.
The pathophysiologic mechanism underlying the association between endotoxaemia and clotting activation in liver cirrhosis is still to be explained.
To investigate the relationship between endotoxaemia, endothelial perturbation and clotting system activation in liver cirrhosis patients.
The study was carried out in 30 consecutive patients (17 males, 13 females, age range 42 to 71 years) with liver cirrhosis.
Prothrombin fragment F1 + 2, endotoxaemia, von Willebrand factor and ristocetin cofactor activity were studied in all patients. Von Willebrand factor antigen release and tissue factor expression were also evaluated in cultured endothelial cells incubated with low endotoxin concentrations (125-500 pg/ml).
Thirteen (43%) out of 30 liver cirrhosis patients showing von Willebrand factor antigen levels > 157 IU/dl (mean +/- 2SD of controls) were considered to have signs of endothelial perturbation; they had more severe liver failure (p = 0.0001), higher ristocetin cofactor activity (p = 0.0001), endotoxin (p = 0.0001) and prothrombin fragment F1 + 2 (p = 0.0001) plasma values than liver cirrhosis with normal von Willebrand factor antigen. A strong correlation (r = 0.97; p = 0.0001) was found between prothrombin fragment F1 + 2 and von Willebrand factor antigen. In in vitro experiments endotoxin induced a concentration-dependent release of von Willebrand factor antigen (p = 0.0001) and expression of tissue factor activity (p = 0.0001) and antigen (p = 0.0001) from cultured endothelial cells.
This study suggests that the endothelial procoagulant activation induced by low-grade endotoxaemia may represent a trigger for systemic clotting activation in liver cirrhosis patients.
肝硬化患者内毒素血症与凝血激活之间关联的病理生理机制仍有待阐明。
研究肝硬化患者内毒素血症、内皮功能紊乱与凝血系统激活之间的关系。
本研究纳入了30例连续的肝硬化患者（17例男性，13例女性，年龄范围42至71岁）。
对所有患者检测凝血酶原片段F1 + 2、内毒素血症、血管性血友病因子及瑞斯托霉素辅因子活性。还用低内毒素浓度（125 - 500 pg/ml）孵育培养的内皮细胞，评估血管性血友病因子抗原释放及组织因子表达。
30例肝硬化患者中，13例（43%）血管性血友病因子抗原水平>157 IU/dl（对照组均值±2SD）被认为有内皮功能紊乱迹象；与血管性血友病因子抗原正常的肝硬化患者相比，他们有更严重的肝功能衰竭（p = 0.0001）、更高的瑞斯托霉素辅因子活性（p = 0.0001）、内毒素（p = 0.0001）及凝血酶原片段F1 + 2（p = 0.
