Marjolein Raps, Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
Thromb Haemost. 2013 Apr;109(4):606-13. doi: 10.1160/TH12-10-0771. Epub 2013 Feb 14.
Use of combined oral contraceptives is associated with a three- to six-fold increased risk of venous thrombosis. Hormonal contraceptives induce acquired resistance to activated protein C (APC), which predicts the risk of venous thrombosis. The biological basis of the acquired APC resistance is unknown. Free protein S (PS) and free tissue factor pathway inhibitor (TFPI) are the two main determinants of APC. Our objective was to assess the effect of both hormonal and non-hormonal contraceptives with different routes of administration on free TFPI and free PS levels. We conducted an observational study in 243 users of different contraceptives and measured APC sensitivity ratios (nAPCsr), free TFPI and free PS levels. Users of contraceptives with the highest risk of venous thrombosis as reported in recent literature, had the lowest free TFPI and free PS levels, and vice versa, women who used contraceptives with the lowest risk of venous thrombosis had the highest free TFPI and free PS levels. An association was observed between levels of free TFPI and nAPCsr, and between free PS and nAPCsr. The effect of oral contraceptives on TFPI and PS is a possible explanation for the increased risk of venous thrombosis associated with oral contraceptives.
联合使用口服避孕药会使静脉血栓形成的风险增加三到六倍。荷尔蒙避孕药会导致激活蛋白 C（APC）的获得性抵抗，而 APC 可以预测静脉血栓形成的风险。获得性 APC 抵抗的生物学基础尚不清楚。游离蛋白 S（PS）和游离组织因子途径抑制剂（TFPI）是 APC 的两个主要决定因素。我们的目的是评估不同给药途径的激素和非激素避孕药对游离 TFPI 和游离 PS 水平的影响。我们在 243 名不同避孕药使用者中进行了一项观察性研究，并测量了 APC 敏感性比（nAPCsr）、游离 TFPI 和游离 PS 水平。根据最近文献报道，静脉血栓形成风险最高的避孕药使用者的游离 TFPI 和游离 PS 水平最低，反之，静脉血栓形成风险最低的避孕药使用者的游离 TFPI 和游离 PS 水平最高。游离 TFPI 水平与 nAPCsr 之间以及游离 PS 与 nAPCsr 之间存在相关性。口服避孕药对 TFPI 和 PS 的影响可能是口服避孕药与静脉血栓形成风险增加相关的原因之一。
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