Bloemenkamp K W, Rosendaal F R, Helmerhorst F M, Koster T, Bertina R M, Vandenbroucke J P
Department of Obstetrics, Gynaecology and Reproductive Medicine, University Hospital Leiden, The Netherlands.
Thromb Haemost. 1998 Sep;80(3):382-7.
Comparison of the effect of oral contraceptives on hemostatic variables in venous thrombosis patients (thrombosis while using oral contraceptives) with the effect in healthy control subjects. Our aim was to assess whether some of these effects were more pronounced in women who had suffered thrombosis, i.e., whether these were "hemostatic hyperresponders".
A population-based case-control study, the Leiden Thrombophilia Study.
We investigated 99 pre-menopausal women, age 15-49 years, who had used oral contraceptives at the time of a first, objectively confirmed episode of deep-vein thrombosis. They were not pregnant, nor in puerperium, nor had had a recent miscarriage, and were not using injectable progestogens, nor suffering from inherited coagulation defects. The median time between occurrence of deep-vein thrombosis and venepuncture was 18 months, and 30 of the 99 women were still using oral contraceptives, while 69 had discontinued oral contraceptive use. In addition, a group of 153 control women (54 of them were oral contraceptive users and 99 were non-users) were studied. The following hemostatic variables were measured: APTT, factor VII, factor VIII, factor XII, fibrinogen, prothrombin, total antithrombin, normalised activated protein C sensitivity ratio (n-APC-sr), protein C, protein S and free protein S.
We found marked and significant effects of oral contraceptive use on the levels of several clotting factors, with an increase in factor VII, factor XII, protein C and a decrease in antithrombin, n-APC-sr and protein S. Less marked effects that were non-significant or only significant in either patients or controls, were an increase in factor VIII, fibrinogen and prothrombin and a decrease in the APTT and free protein S. In the former thrombosis patients several of these effects of oral contraceptives were more pronounced than in healthy women: specifically on factor VII, antithrombin, n-APC-sr and protein C.
Our results of the effects of oral contraceptives generally confirm previous reports in healthy volunteers. Our data also show that in former deep-vein thrombosis patients these effects are more pronounced. Apparently some women become "high hemostatic responders" when exposed to oral contraceptives, and they may be the women most vulnerable to its thrombogenic effects.
比较口服避孕药对静脉血栓形成患者（使用口服避孕药时发生血栓形成）止血变量的影响与对健康对照者的影响。我们的目的是评估这些影响在曾患血栓形成的女性中是否更显著，即她们是否为“高止血反应者”。
一项基于人群的病例对照研究，即莱顿血栓形成倾向研究。
我们调查了99名年龄在15至49岁之间的绝经前女性，她们在首次经客观确认的深静脉血栓形成发作时使用了口服避孕药。她们未怀孕，不在产褥期，近期也未流产，未使用注射用孕激素，也未患有遗传性凝血缺陷。深静脉血栓形成与静脉穿刺之间的中位时间为18个月，99名女性中有30名仍在使用口服避孕药，而69名已停止使用。此外，还研究了一组153名对照女性（其中54名是口服避孕药使用者，99名是非使用者）。测量了以下止血变量：活化部分凝血活酶时间（APTT）、凝血因子VII、凝血因子VIII、凝血因子XII、纤维蛋白原、凝血酶原、总抗凝血酶、标准化活化蛋白C敏感率（n-APC-sr）、蛋白C、蛋白S和游离蛋白S。
我们发现使用口服避孕药对几种凝血因子水平有显著影响，凝血因子VII、凝血因子XII、蛋白C升高，抗凝血酶、n-APC-sr和蛋白S降低。不太显著的影响（在患者或对照中不显著或仅在一方显著）包括凝血因子VIII、纤维蛋白原和凝血酶原升高，APTT和游离蛋白S降低。在既往血栓形成患者中，口服避孕药的这些影响中有几种比健康女性更显著：特别是对凝血因子VII、抗凝血酶、n-APC-sr和蛋白C。
我们关于口服避孕药影响的结果总体上证实了先前在健康志愿者中的报道。我们的数据还表明，在既往深静脉血栓形成患者中这些影响更显著。显然，一些女性在接触口服避孕药时会成为“高止血反应者”，她们可能是最易受其血栓形成作用影响的女性。
