Hart J E
Department of Biochemistry, University of Surrey, Guildford, UK.
Thromb Haemost. 1987 Jun 3;57(3):273-7.
Hexoestrol, diethylstilboestrol and ethinyloestradiol administered orally at a dose of 60 mg/kg/day to groups of five rats caused decreases in vitamin K-dependent blood clotting as measured by the Thrombotest reaction. These changes were self-limiting over a twenty-day study period and were not associated with external signs of bleeding. Pretreatment with testosterone and vitamin K1 did not significantly affect the clotting changes, but the antioestrogen clomiphene citrate exacerbated these, in several cases to lethal effect. Death was associated with haemorrhage. Hexoestrol-treated rats receiving clomiphene citrate in a sub-experiment did not show the increase in liver weight seen in animals given hexoestrol alone. In another sub-experiment, the level of clotting factor VII activity in the plasma of rats receiving hexoestrol at 60 mg/kg/day for four days was shown to be about half that of controls. There was probably no abnormal clotting inhibitor activity. It was deduced that the reduction in factor VII activity was more likely to be due to a decrease in synthesis as a result of liver dysfunction than changes in vitamin K availability. Clomiphene citrate may exacerbate the liver-dependent clotting disorders induced by oestrogens by preventing an adaptive increase in liver mass. It is concluded that the rat is a poor model species for investigating the blood clotting disorders seen in humans treated with oestrogens.
己烷雌酚、己烯雌酚和炔雌醇以60毫克/千克/天的剂量口服给予每组五只大鼠，通过凝血酶检测反应测定，可导致维生素K依赖的血液凝固性降低。在为期20天的研究期间，这些变化是自限性的，且与出血的外部体征无关。用睾酮和维生素K1进行预处理对凝血变化没有显著影响，但抗雌激素克罗米芬柠檬酸盐会加剧这些变化，在某些情况下会导致致命后果。死亡与出血有关。在一项子实验中，接受己烷雌酚治疗的大鼠同时接受克罗米芬柠檬酸盐，未出现单独给予己烷雌酚的动物所出现的肝脏重量增加。在另一项子实验中，接受60毫克/千克/天己烷雌酚治疗四天的大鼠血浆中凝血因子VII活性水平约为对照组的一半。可能不存在异常的凝血抑制活性。据推断，因子VII活性降低更可能是由于肝功能障碍导致合成减少，而非维生素K可用性的变化。克罗米芬柠檬酸盐可能通过阻止肝脏质量的适应性增加而加剧雌激素诱导的依赖肝脏的凝血障碍。得出的结论是，大鼠是研究接受雌激素治疗的人类所出现的血液凝固障碍的不良模型物种。
