Increased Fibrinolytic Activity during Use of Oral Contraceptives Is Counteracted by an Enhanced Factor XI-independent down Regulation of Fibrinolysis
Increased Fibrinolytic Activity during Use of Oral Contraceptives Is Counteracted by an Enhanced Factor XI-independent down Regulation of Fibrinolysis
复制标题
使用口服避孕药期间增加的纤溶活性被增强的 XI 因子独立的纤溶下调所抵消
DOI：
10.1055/s-0037-1613959
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发表时间：
2000
影响因子：
6.7
通讯作者：
B. Bouma
中科院分区：
文献类型：
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作者：
J. Meijers;S. Middeldorp;W. Tekelenburg;A. van den Ende;G. Tans;M. Prins;J. Rosing;H. Büller;B. Bouma
在一项周期对照交叉研究中，研究人员调查了口服避孕药（OC）对纤溶参数的影响。在这项研究中，28名未服用口服避孕药的女性随机服用第二代口服避孕药（30µg炔雌醇，150µg左炔诺孕酮）或第三代口服避孕药（30µg炔雌醇，150µg去吉奥孕酮），并在两个月的洗脱期后更换口服避孕药。在使用OC期间，组织型纤溶酶原激活物（tPA）活性、纤溶酶原、纤溶酶-α2-抗纤溶酶复合物和d -二聚体水平显著升高（30% ~ 80%），而纤溶酶原激活物抑制剂-1 （PAI-1）抗原、PAI-1活性和tPA抗原水平显著降低（25% ~ 50%），提示内源性纤溶活性升高。这些oc引起的变化在两种避孕药之间没有区别。TAFI（凝血酶激活纤溶抑制剂）水平在左炔诺孕酮组升高，在去索孕酮组甚至进一步升高。一项检测纤溶活性和凝血系统产生凝血酶（通过TAFI下调纤溶所需的凝血酶）功效的凝血溶解试验显示，在使用OC期间，凝血溶解时间没有变化。这一发现表明，oc诱导的内源性纤溶活性的增加被凝血系统通过TAFI下调纤溶能力的增加所抵消。事实上，我们观察到，在使用OC期间，凝块形成过程中F1+2的产生显著增加。当这些试验在抗因子XI抗体存在的情况下进行时，我们观察到在使用OC期间凝块溶解时间显着增加，并且在OC治疗期间F1+2生成的增加是由于因子XI不相关的过程，去索孕酮明显高于左炔诺孕酮。这些数据表明OC诱导的内源性纤维蛋白溶解的抑制以一种不依赖于因子xi的方式发生，并且在去索孕酮上比在含左炔诺孕酮的OC上更明显。
Summary The effect of oral contraceptives (OC) on fibrinolytic parameters was investigated in a cycle-controlled cross-over study in which 28 non-OC using women were randomly prescribed either a representative of the so-called second (30 µg ethinylestradiol, 150 µg levonorgestrel) or third generation OC (30 µg ethinylestradiol, 150 µg desogestrel) and who switched OC after a two month wash out period. During the use of OC, the levels of tissue-type plasminogen activator (tPA) activity, plasminogen, plasmin-α2-antiplasmin complexes and D-dimer significantly increased (by 30 to 80%), while the levels of plasminogen activator inhibitor-1 (PAI-1) antigen, PAI-1 activity and tPA antigen significantly decreased (25 to 50%), suggesting an increase in endogenous fibrinolytic activity. These OC-induced changes were not different between the two contraceptive pills. TAFI (thrombin-activatable fibrinolysis inhibitor) levels increased on levonorgestrel, and even further increased on desogestrel. A clot lysis assay that probes both fibrinolytic activity and the efficacy of the coagulation system to generate thrombin necessary to down regulate fibrinolysis via TAFI showed no change of the clot lysis time during OC use. This finding suggests that the OC-induced increase in endogenous fibrinolytic activity is counteracted by an increased capacity of the coagulation system to down regulate fibrinolysis via TAFI. Indeed we observed that during OC use there was a significant increase of F1+2 generation during clot formation. When these assays were performed in the presence of an antibody against factor XI, we observed that the clot lysis time was significantly increased during OC use and that the increase in F1+2 generation during OC therapy was due to a factor XI-independent process, which was significantly higher on desogestrel than on levonorgestrel. These data indicate that the OC-induced inhibition of endogenous fibrinolysis takes place in a factor XI-independent way and is more pronounced on desogestrel than on levonorgestrel-containing OC.
缺血性中风和复方口服避孕药：一项国际多中心病例对照研究的结果。
DOI：
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发表时间：
1996
期刊：
Lancet (London, England)
影响因子：
--
作者：
通讯作者：
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