荷兰拉德布大学医学中心Saskia Middeldorp团队研究了肝素治疗复发性流产和遗传性血栓病的疗效。2023年6月1日出版的《柳叶刀》杂志发表了这项成果。

抗凝治疗可以减少复发性流产和遗传性血栓形成倾向妇女的流产次数和不良妊娠结局。该研究旨在评估低分子肝素（LMWH）与标准治疗在该人群中的使用情况。

ALIFE2试验是一项国际开放标签随机对照试验，在英国（n=26）、荷兰（n=10）、美国（n=2）、比利时（n=1）和斯洛文尼亚（n=1）的医院进行。年龄在18-42岁之间，如果有两次或两次以上的妊娠丢失并确认遗传性血栓形成倾向，并且正在尝试怀孕或已经怀孕（≤7周妊娠）的女性，则有资格入组。

一旦尿液妊娠测试呈阳性，女性则被随机分配（1:1）使用或不使用低剂量低分子肝素（与两组的标准护理一起）。低分子肝素在妊娠7周或之前开始，一直持续到妊娠结束。主要结局指标是活产率，根据现有数据对所有女性进行评估。安全性结局包括出血、血小板减少和皮肤反应，并在所有报告安全性事件的随机分配女性中进行了评估。

2012年8月1日至2021年1月30日，10625名妇女接受了资格评估，428人进行了登记，326人怀孕并被随机分配（164人接受低分子肝素治疗，162人接受标准护理）。低分子肝素组162名有主要结局数据的妇女中有116名（72%）活产，标准护理组158名妇女中有112名（71%）（校正后的比值比为1.08；绝对风险差0.7%）。低分子肝素组164名女性中有39名（24%）和标准护理组162名女性中的37名（23%）报告了不良事件。

研究结果表明，在两次及以上流产并证实遗传性血栓形成倾向的妇女中，低分子肝素并没有导致更高的活产率。研究组不建议在复发性流产和遗传性血栓形成倾向的妇女中使用低分子肝素，并建议不要在复发性妊娠流产的妇女中筛查遗传性血栓生成倾向。

附：英文原文

Title: Heparin for women with recurrent miscarriage and inherited thrombophilia (ALIFE2): an international open-label, randomised controlled trial

Author: Siobhan Quenby, Katie Booth, Louise Hiller, Arri Coomarasamy, Paulien G de Jong, Eva N Hamulyák, Luuk J Scheres, Thijs F van Haaps, Lauren Ewington, Shreeya Tewary, Maritte Goddijn, Saskia Middeldorp

Issue&Volume: 2023-06-01

Abstract:

Background

Anticoagulant therapy might reduce the number of miscarriages and adverse pregnancy outcomes in women with recurrent pregnancy loss and inherited thrombophilia. We aimed to assess use of low-molecular-weight heparin (LMWH) versus standard care in this population.

Methods

The ALIFE2 trial was an international open-label, randomised controlled trial undertaken in hospitals in the UK (n=26), the Netherlands (n=10), the USA (n=2), Belgium (n=1), and Slovenia (n=1). Women aged 18–42 years who had two or more pregnancy losses and confirmed inherited thrombophilia, and who were trying to conceive or were already pregnant (≤7 weeks' gestation), were eligible for inclusion. Women were randomly assigned (1:1) to use low-dose LMWH or not (alongside standard care in both groups) once they had a positive urine pregnancy test. LMWH was started at or before 7 weeks' gestation and continued until the end of pregnancy. The primary outcome measure was livebirth rate, assessed in all women with available data. Safety outcomes included bleeding episodes, thrombocytopenia, and skin reactions, and were assessed in all randomly assigned women who reported a safety event. The trial was registered within the Dutch Trial Register (NTR3361) and EudraCT (UK: 2015-002357-35).

Findings

Between Aug 1, 2012, and Jan 30, 2021, 10625 women were assessed for eligibility, 428 were registered, and 326 conceived and were randomly assigned (164 to LMWH and 162 to standard care). 116 (72%) of 162 women with primary outcome data in the LMWH group and 112 (71%) of 158 in the standard care group had livebirths (adjusted odds ratio 1·08, 95% CI 0·65 to 1·78; absolute risk difference, 0·7%, 95% CI –9·2% to 10·6%). 39 (24%) of 164 women in the LMWH group and 37 (23%) of 162 women in the standard care group reported adverse events.

Interpretation

LMWH did not result in higher livebirth rates in women who had two or more pregnancy losses and confirmed inherited thrombophilia. We do not advise use of LMWH in women with recurrent pregnancy loss and inherited thrombophilia, and we advise against screening for inherited thrombophilia in women with recurrent pregnancy loss.

DOI: 10.1016/S0140-6736(23)00693-1

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00693-1/fulltext