Department of Hemostaseology, Institute of Transfusion Medicine, Charité University Hospital Berlin, Berlin, Germany.
Clin Appl Thromb Hemost. 2009 Dec;15(6):636-44. doi: 10.1177/1076029609335501. Epub 2009 Aug 9.
In women with a history of recurrent miscarriage, the risk of miscarriage in a subsequent pregnancy is about 30% to 40%. In patients with thrombophilia, the risk is even higher. Placental thrombosis has been found in women with unexplained recurrent miscarriage independent of thrombophilia. In addition, proinflammatory changes, for example, altered Th1 to Th2 cytokine ratio and complement activation, have been repeatedly demonstrated in these women. Because of the fact that heparin has both anticoagulative and anti-inflammatory effects, the current study evaluated the efficacy of low-molecular-weight heparin (LMWH) in unexplained abortions.
A total of 164 women with unexplained early and late miscarriages presented in our hemostaseological clinic for thrombophilia screening. For these 164 women, 82 subsequent pregnancies in 79 patients were treated with subcutaneous LMWH independently of thrombophilia. In 54/82 unselected pregnancies, 100 mg aspirin was administered in addition to LMWH. Two patients were excluded due to termination of pregnancy.
Overall, 83.8% (67/80) of pregnancies resulted in live births. In 22/79 women (27.8%), thrombophilia markers were positive. Most noteworthy, patients with thrombophilia markers had live births at a similar frequency as patients without those parameters. No severe side effects of LMWH were seen.
Our data support the notion that LMWH is efficacious in patients with recurrent abortions and thrombophilia. We demonstrated the same effect of LMWH in women with unexplained abortions without thrombophilia. The potential mechanism of action of LMWH in early and late abortions warrants further study.
在有反复流产史的女性中，随后妊娠的流产风险约为 30%至 40%。在血栓形成倾向的患者中，风险甚至更高。在与血栓形成倾向无关的不明原因反复流产的女性中，已经发现胎盘血栓形成。此外，这些女性中反复出现促炎变化，例如改变的 Th1 至 Th2 细胞因子比值和补体激活。由于肝素具有抗凝和抗炎作用，因此本研究评估了低分子量肝素（LMWH）在不明原因流产中的疗效。
共有 164 名患有不明原因早期和晚期流产的女性在我们的止血诊所就诊进行血栓形成倾向筛查。对于这 164 名女性，79 名患者中的 82 次后续妊娠在未考虑血栓形成倾向的情况下接受皮下 LMWH 治疗。在 54/82 例未经选择的妊娠中，除 LMWH 外还给予 100mg 阿司匹林。由于终止妊娠，有 2 名患者被排除在外。
总体而言，83.8%（67/80）的妊娠导致活产。在 79 名女性中的 22 名（27.8%）中，血栓形成倾向标志物呈阳性。最值得注意的是，有血栓形成倾向标志物的患者与没有这些参数的患者的活产率相似。未观察到 LMWH 的严重副作用。
我们的数据支持 LMWH 对反复流产和血栓形成倾向患者有效的观点。我们证明了 LMWH 在无血栓形成倾向的不明原因流产女性中同样有效。LMWH 在早期和晚期流产中的潜在作用机制值得进一步研究。
