Koh Kwang Kon
Gil Heart Center, Gachon Medical School, Incheon, Korea.
Int J Hematol. 2002 Aug;76 Suppl 2:44-6. doi: 10.1007/BF03165085.
It has been speculated that hormone replacement therapy (HRT) containing relatively low dose of estrogen would be different from oral contraceptive pills in causing thromboembolism because activation of coagulation depends on the amount of estrogen. In contrast to this knowledge, activation of coagulation pathways has been detected in postmenopausal women treated with HRT in the observational and clinical studies. In this regard, recent studies have reported a 2 to approximately 4 fold risk of venous thromboembolism or pulmonary embolism in postmenopausal women receiving HRT than in non-users of estrogen. On the other hands, HRT has shown to enhance systemic fibrinolysis with decreased plasma plasminogen activator inhibitor-1 (PAI-1) levels. In addition, levels of D-dimer exhibited a significant inverse correlation with PAI-1 levels, suggesting enhanced fibrinolysis potential. However, small doses of estrogen/progestogen induce increases in fibrinolytic capacity via a marked reduction of PAI-1. In other words, HRT at conventional dosages may affect fibrinolytic activity to a greater extent than coagulation activity, whereas the converse trend holds at higher estrogen doses. The increase in fibrinolytic potential was independent of any effect on coagulation of CEE at conventional dosages. However, in contrast to healthy postmenopausal women, we recently reported that HRT did not significantly decrease PAI-1 antigen levels and rather, increased tissue factor activity and prothrombin fragment F(1+2) levels from baseline in hypertensive and/or overweight postmenopausal women. Activation of coagulation following HRT may not be balanced by activation of fibrinolysis in some postmenopausal women. Thrombogenic events are considered more likely in patients with certain heritable conditions, such as platelet antigen-2 (PIA-2) polymorphisms. Further, Factor V Leiden mutation increases the risk of primary and recurrent venous thromboembolic events by three to sixfold and the risk of myocardial infarction. Indeed, HRT may decrease or increase atherothrombosis risk depending on the presence of Factor V Leiden mutation. Thus, HRT should not be initiated in women with established coronary artery disease or the coexistence of other risk factors for hypercoagulability-malignancy, immobility, obesity, diabetes, advanced age, or inherited traits. However, HRT at conventional dosages improves fibrinolysis potential in healthy postmenopausal women.
据推测，含相对低剂量雌激素的激素替代疗法（HRT）在引发血栓栓塞方面可能与口服避孕药不同，因为凝血激活取决于雌激素的量。与这一认知相反，在观察性研究和临床研究中，已在接受HRT治疗的绝经后女性中检测到凝血途径的激活。在这方面，最近的研究报告称，接受HRT的绝经后女性发生静脉血栓栓塞或肺栓塞的风险比未使用雌激素的女性高2至约4倍。另一方面，HRT已显示可增强全身纤维蛋白溶解，同时血浆纤溶酶原激活物抑制剂-1（PAI-1）水平降低。此外，D-二聚体水平与PAI-1水平呈显著负相关，表明纤维蛋白溶解潜力增强。然而，小剂量雌激素/孕激素通过显著降低PAI-1诱导纤维蛋白溶解能力增加。换句话说，常规剂量的HRT对纤维蛋白溶解活性的影响可能比对凝血活性的影响更大，而在更高雌激素剂量下则呈现相反趋势。常规剂量的结合雌激素（CEE）对纤维蛋白溶解潜力的增加与对凝血的任何影响无关。然而，与健康的绝经后女性不同，我们最近报告称，在高血压和/或超重的绝经后女性中，HRT并没有显著降低PAI-1抗原水平，反而使组织因子活性和凝血酶原片段F(1+2)水平较基线升高。在一些绝经后女性中，HRT后的凝血激活可能无法通过纤维蛋白溶解激活来平衡。在患有某些遗传性疾病的患者中，如血小板抗原-2（PIA-2）多态性，血栓形成事件被认为更有可能发生。此外，凝血因子V莱顿突变使原发性和复发性静脉血栓栓塞事件的风险增加三至六倍，并增加心肌梗死风险。事实上，根据凝血因子V莱顿突变的存在情况，HRT可能会降低或增加动脉粥样硬化血栓形成风险。因此，对于已患有冠状动脉疾病或同时存在其他高凝风险因素（恶性肿瘤、活动减少、肥胖、糖尿病、高龄或遗传特征）的女性，不应开始使用HRT。然而，常规剂量的HRT可改善健康绝经后女性的纤维蛋白溶解潜力。
