Rosing J, Tans G, Nicolaes G A, Thomassen M C, van Oerle R, van der Ploeg P M, Heijnen P, Hamulyak K, Hemker H C
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
Br J Haematol. 1997 Apr;97(1):233-8. doi: 10.1046/j.1365-2141.1997.192707.x.
Epidemiological studies have shown that women who use third-generation oral contraceptives (OC) containing desogestrel, gestodene or norgestimate have a higher risk of venous thrombosis than women who use second-generation OC containing levonorgestrel. It is also known that a mutation in factor V (factor V(Leiden)), which results in resistance to activated protein C (APC) and which is the most common cause of hereditary thrombophilia, potentiates the prothrombotic effect of OC. Effects of APC on thrombin generation in the plasma of women using OC were compared to the response to APC in non-OC users and in individuals that were heterozygous or homozygous for factor V(Leiden). The response towards APC was evaluated on basis of the ratio (APC-sr) of the time integrals of thrombin formation determined in the presence and absence of APC. Compared with women not using OC, women who used OC exhibited a significantly decreased sensitivity to APC (P<0.001), independent of the kind of OC used. Women who used third-generation monophasic OC were significantly less sensitive to APC than women using second-generation OC (P<0.001) and had APC-sr that did not significantly differ from heterozygous female carriers of factor V(Leiden) who did not use OC. Women who were heterozygous for factor V(Leiden) and used OC had APC-sr in the range of homozygous carriers of factor V(Leiden). Two women who started OC therapy had significantly elevated APC-sr within 3 d. Acquired APC resistance may explain the epidemiological observation of increased risk for venous thrombosis in OC users, especially in women using third-generation OC.
流行病学研究表明，使用含去氧孕烯、孕二烯酮或诺孕酯的第三代口服避孕药（OC）的女性比使用含左炔诺孕酮的第二代OC的女性发生静脉血栓形成的风险更高。还已知，因子V（因子V（莱顿））的突变导致对活化蛋白C（APC）的抵抗，这是遗传性血栓形成倾向的最常见原因，会增强OC的促血栓形成作用。将使用OC的女性血浆中APC对凝血酶生成的影响与未使用OC的女性以及因子V（莱顿）杂合或纯合个体对APC的反应进行了比较。根据在有和没有APC的情况下测定的凝血酶形成时间积分的比率（APC-sr）来评估对APC的反应。与未使用OC的女性相比，使用OC的女性对APC的敏感性显著降低（P<0.001），与所使用的OC类型无关。使用第三代单相OC的女性对APC的敏感性明显低于使用第二代OC的女性（P<0.001），其APC-sr与未使用OC的因子V（莱顿）杂合女性携带者没有显著差异。因子V（莱顿）杂合且使用OC的女性的APC-sr在因子V（莱顿）纯合携带者范围内。两名开始OC治疗的女性在3天内APC-sr显著升高。获得性APC抵抗可能解释了OC使用者，尤其是使用第三代OC的女性静脉血栓形成风险增加的流行病学观察结果。
