Spannagl M, Dick A, Assmann A, Heinemann L, Schramm W
Ludwig Maximilians University Munich, Klinikum Innenstadt, Dept. of Hemostasis and Angiology, Germany.
Semin Thromb Hemost. 1998;24(5):423-30. doi: 10.1055/s-2007-996034.
Resistance to activated protein C (APC resistance) is an important and common risk factor for deep vein thrombosis. The majority of patients with APC resistance carry a mutation on the factor V gene at nucleotide position 1691 (G/A), called factor V Leiden mutation. Besides the factor V Leiden mutation several acquired risk factors like lupus anticoagulant, elevated levels of acute phase proteins (increased plasma levels of factor VIII and fibrinogen), pregnancy, or the use of oral contraceptives are known to induce APC resistance in plasma. We studied the effect of oral contraceptives (OC) on hemostasis variables known to be risk factors for venous thromboembolism, especially looking for acquired APC resistance and the plasmatic factors of the protein C system. We studied 821 women, who were randomly selected and enrolled in the BATER- cohort study (Bavarian Thromboembolic Risk Study), which was carried out in Bavaria (Germany) from 1996 to 1997. Current use of any OC type compared with noncurrent use showed a significantly impaired response to APC. There was no difference in APC response among women currently using OCs of different generations. Coagulation factor VIII was the only factor of the protein C pathway that was not altered under OC use. All other plasmatic factors of the protein C system changed in the expected range as described before. On the other hand, coagulation factor VIII was the only factor of the protein C system which negatively correlated with the APC response in the assays applied. Thus, APC resistance is significantly lower in OC users than in nonusers but cannot be attributed to increased factor VIII levels. Whether a decreased response to APC in OC users is of clinical relevance has to be proven in further studies.
对活化蛋白C的抵抗（APC抵抗）是深静脉血栓形成的一个重要且常见的危险因素。大多数APC抵抗患者在凝血因子V基因的核苷酸位置1691（G/A）处携带一种突变，称为凝血因子V莱顿突变。除了凝血因子V莱顿突变外，一些获得性危险因素，如狼疮抗凝物、急性期蛋白水平升高（血浆中凝血因子VIII和纤维蛋白原水平升高）、妊娠或使用口服避孕药，已知可在血浆中诱导APC抵抗。我们研究了口服避孕药（OC）对已知为静脉血栓栓塞危险因素的止血变量的影响，尤其关注获得性APC抵抗和蛋白C系统的血浆因子。我们研究了821名女性，她们是从1996年至1997年在德国巴伐利亚进行的BATER队列研究（巴伐利亚血栓栓塞风险研究）中随机选取并纳入的。与未使用任何OC的情况相比，当前使用任何类型OC的女性对APC的反应明显受损。当前使用不同代OC的女性之间在APC反应方面没有差异。凝血因子VIII是蛋白C途径中唯一在使用OC时未发生改变的因子。蛋白C系统的所有其他血浆因子如之前所描述的那样在预期范围内发生了变化。另一方面，在应用的检测中，凝血因子VIII是蛋白C系统中唯一与APC反应呈负相关的因子。因此，OC使用者的APC抵抗明显低于未使用者，但不能归因于凝血因子VIII水平的升高。OC使用者对APC反应降低是否具有临床相关性还需在进一步研究中得到证实。
