This study aimed to identify specific haemostatic changes that might account for previous observations of higher venous thromboembolic risk among users of combined oral contraceptives (COCs) containing desogestrel (DSG) than levonorgestrel (LNG). Sixty-three current users of monophasic 30 microg oestrogen COCs containing either LNG or DSG omitted one pill-free interval (PFI), switching immediately either to the opposite formulation for one cycle or continuing with the same pill. Venesection followed the initial PFI after one cycle (21 tablets) and two cycles (42 tablets) of continuous pill taking, and after the following PFI. Protein S was lower in users of DSG than LNG formulations after the first PFI (mean +/- SD, 0.67 +/- 0.09 vs 0.76 +/- 0.10, P < 0.001) and after one cycle (0.61 +/- 0.09 vs 0.76 +/- 0.09, P < 0.0001). Protein S decreased when switching from LNG to DSG pills (0.77 +/- 0.07-0.65 +/- 0.06, P < 0.0001), mirrored by an increase at switching from DSG to LNG formulations (0.61 +/- 0.08-0.73 +/- 0.10, P < 0.005). Mean protein S levels remained within the normal range. Three different markers of thrombin generation remained unaltered. Potential explanations for COC-related thrombotic events are 'acquired resistance to activated protein C' or inhibition of fibrinolysis. A potential role has been described for protein S deficiency in both. A further triggering factor is a probable prerequisite for actual thrombosis, but pill-takers whose levels of protein S were in the lowest percentiles may be at greatest risk.

译文

:本研究旨在确定特定的止血变化,这些变化可能解释了先前观察到的患者中,使用去氧孕烯(DSG)联合左炔诺孕酮(LNG)的联合口服避孕药(COC)使用者的静脉血栓栓塞风险更高。目前有63位使用LNG或DSG的单相30微克雌激素COC使用者省略了一个无丸间隔(PFI),立即切换到相反的配方进行一个周期或继续使用同一丸。在连续服药一个周期(21片)和两个周期(42片)之后,以及随后的PFI之后,Venesection遵循最初的PFI。 DSG使用者在第一次PFI之后的蛋白S低于LNG制剂(平均值/-SD,0.67 /-0.09 vs 0.76 /-0.10,P <0.001),并且在一个周期后(0.61 // 0.09 vs 0.76 /-0.09, P <0.0001)。从LNG换成DSG药丸时,蛋白质S减少(0.77 /-0.07-0.65 /-0.06,P <0.0001),这反映了从DSG换成LNG制剂时的增加(0.61 /-0.08-0.73 /-0.10,P < 0.005)。平均蛋白S水平保持在正常范围内。凝血酶生成的三个不同标记保持不变。 COC相关血栓形成事件的潜在解释是“获得的对活化蛋白C的抗性”或纤维蛋白溶解的抑制。已经描述了两者中蛋白质S缺乏症的潜在作用。另一个触发因素是实际血栓形成的可能先决条件,但蛋白质S水平最低的服用避孕药者风险最高。

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