Decreased plasma tissue factor pathway inhibitor in women taking combined oral contraceptives
Decreased plasma tissue factor pathway inhibitor in women taking combined oral contraceptives
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DOI：
10.1002/(sici)1096-8652(199903)60:3
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发表时间：
1999-03-01
影响因子：
12.8
通讯作者：
Tipping, PG
中科院分区：
文献类型：
--
作者：
Harris, GM;Stendt, CL;Tipping, PG
使用复方口服避孕药（OC）与血栓形成的显着风险相关。这种效应的机制尚不清楚。组织因子途径抑制剂 (TFPI) 是一种循环抗凝剂，可抑制外源性凝血途径激活的最早步骤，它在凝血控制中发挥核心作用，但其对 OC 相关血栓形成风险的贡献尚未评估。通过标准测定法测量血浆 TFPI 抗原和活性、因子 VIIa、凝血酶原片段 1&2、血管性血友病抗原、纤维蛋白原和低密度脂蛋白胆固醇。服用 OC 的女性（年龄 16 至 45 岁，n = 40）和年龄匹配的未服用 OC 的女性（对照组，n = 40）。对照组的血浆 TFPI 抗原在整个月经周期中没有显着变化。服用 OC 的女性血浆 TFPI 抗原降低 25%（中位数 51.0 ng/ml；95% 置信区间 [CI] 37.5 至 85.5；对照 68.0 ng/ml，CI 61.0 至 95.0；P < 0.001），TFPI 活性降低 29%（78.5 U/ml，CI 57.5 至107.5；对照 111.0 U/ml，CI 79.5 至 171.0；与对照相比，P < 0.001。在使用 OC 的女性中，血浆因子 VIIa 活性和凝血酶原片段 1 和 2 也显着增加（均 P < 0.001），表明外源性凝血途径的激活。这些结果表明，雌激素和/或孕激素的正常周期性变化不会显着改变血浆 TFPI 水平。然而，OC 中的雌激素和/或孕激素会激活外源性凝血途径，并显着降低血浆 TFPI（其主要循环抑制剂）。血浆 TFPI 水平降低可能是 OC 血栓形成作用的基础。是。 J.赫马托尔。 60:175-180, 1999。(C) 1999 Wiley-Liss, Inc.
Use of combined oral contraceptives (OC) is associated with a significant risk of thrombosis. The mechanisms of this effect are not clearly defined. Tissue factor pathway inhibitor (TFPI) is a circulating anti-coagulant that inhibits the earliest steps in activation of the extrinsic coagulation pathway, It plays a central role in control of coagulation but its contribution to the thrombotic risk associated with OC has not been assessed, Plasma TFPI antigen and activity, factor VIIa, prothrombin fragments 1&2, von Willebrand antigen, fibrinogen, and low density lipoprotein cholesterol were measured by standard assays in women taking OC (aged 16 to 45 years, n = 40) and age-matched women not taking OC (controls, n = 40). Plasma TFPI antigen did not vary significantly across the menstrual cycle in controls. Women on OC had a 25% reduction in plasma TFPI antigen (median 51.0 ng/ml; 95% confidence intervals [CI] 37.5 to 85.5; control 68.0 ng/ml, CI 61.0 to 95.0; P < 0.001) and a 29% reduction in TFPI activity (78.5 U/ml, CI 57.5 to 107.5; control 111.0 U/ml, CI 79.5 to 171.0; P < 0.001) compared to controls. Plasma factor VIIa activity and prothrombin fragments 1&2 were also significantly increased in women using OC (both P < 0.001), indicating activation of the extrinsic coagulation pathway, These results demonstrate that normal cyclic variations in estrogen and/or progesterone do not significantly alter plasma TFPI levels. However, estrogens and/or progestogens in OC result in activation of the extrinsic coagulation pathway and significantly reduce plasma TFPI, its major circulating inhibitor. Reduced plasma TFPI levels may underlie the thrombotic effects of OC. Am. J. Hematol. 60:175-180, 1999. (C) 1999 Wiley-Liss, Inc.