Middeldorp S, Rosing J, Bouma B N, Büller H R
Academisch Medisch Centrum, afd. Vasculaire Geneeskunde, Postbus 22.660, 1100 DD Amsterdam.
Ned Tijdschr Geneeskd. 2001 Feb 10;145(6):252-6.
Use of oral contraceptives induce changes in haemostatic parameters: changes occur in the procoagulant, anticoagulant, and fibrinolytic systems. The increased risk of venous thromboembolism with use of third, as compared with second generation oral contraceptives, found in epidemiological studies, has stimulated new research in haemostatic changes induced by both generations of oral contraceptives. A randomized crossover study showed that use of the third generation pill caused a greater increase of factor VII and prothrombin and a more pronounced decrease of factor V than the second generation pill. Acquired resistance to activated protein C (APC) was induced more strongly by preparations of the third than by those of the second generation. The concentration of protein S decreased markedly exclusively during use of the third generation pill, while it did not change during use of the second generation pill. The oral contraception-related effects on the anticoagulant system strongly resemble those of some forms of hereditary thrombophilia. If a woman with hereditary APC resistance (caused by factor V Leiden) uses oral contraceptives as well, and especially when she uses those of the third generation, she is subject to a considerable increase of the risk of venous thrombosis and becomes even more resistant to the anticoagulant action of protein C. In view of the epidemiological backgrounds of the difference in risk of thrombosis between second and third generation contraceptives, the second generation pill is recommended as the first choice for oral contraception.
促凝、抗凝和纤溶系统均会出现改变。流行病学研究发现，与第二代口服避孕药相比，第三代口服避孕药使用者发生静脉血栓栓塞的风险增加，这激发了对两代口服避孕药引起的止血变化的新研究。一项随机交叉研究表明，与第二代避孕药相比，第三代避孕药会使因子VII和凝血酶原增加更多，因子V降低更显著。第三代制剂比第二代制剂更强烈地诱导获得性活化蛋白C（APC）抵抗。仅在使用第三代避孕药期间，蛋白S的浓度会显著降低，而在使用第二代避孕药期间则没有变化。口服避孕药对抗凝系统的影响与某些遗传性血栓形成倾向的影响非常相似。如果一名患有遗传性APC抵抗（由因子V莱顿突变引起）的女性也使用口服避孕药，尤其是使用第三代避孕药时，她发生静脉血栓形成的风险会大幅增加，并且对蛋白C的抗凝作用更具抵抗性。鉴于第二代和第三代避孕药在血栓形成风险上存在差异的流行病学背景，推荐第二代避孕药作为口服避孕的首选。
