Pasquier Elisabeth, de Saint Martin Luc, Bohec Caroline, Chauleur Céline, Bretelle Florence, Marhic Gisèle, Le Gal Grégoire, Debarge Véronique, Lecomte Frédéric, Denoual-Ziad Christine, Lejeune-Saada Véronique, Douvier Serge, Heisert Michel, Mottier Dominique
EA 3878 Groupe d'Etude de la Thrombose de Bretagne Occidentale, Department of Internal Medicine and Chest Diseases, Brest University Hospital, La Cavale Blanche Hospital, Brest, France;
Division of Gynaecology, François Mitterand Hospital, Pau, France;
Blood. 2015 Apr 2;125(14):2200-5. doi: 10.1182/blood-2014-11-610857. Epub 2015 Jan 30.
It is common practice in many centers to offer antithrombotic medications to women with unexplained recurrent miscarriage, in the presence or absence of inherited thrombophilia. Although no benefit of aspirin vs placebo has been clearly demonstrated, a double-blind placebo-controlled trial on the effect of low-molecular-weight heparin is lacking. We enrolled 258 pregnant women with a history of unexplained recurrent miscarriage (≥2 consecutive miscarriages before 15 weeks' gestation) and a negative thrombophilia workup. They were randomly assigned to receive one daily subcutaneous injection of enoxaparin 40 mg or placebo until 35 weeks' gestation. We included 256 women (mean age 32 years, ≥3 miscarriages: 72%; mean gestational age 39 days of amenorrhea) in the intention-to-treat analysis; 66.6% of 138 who received enoxaparin had a live birth vs 72.9% of 118 who received placebo. The absolute difference was -6% (95% CI, -17.1 to 5.1), excluding a 10% increase in the rate of live-birth on enoxaparin (P = .34). In this first randomized, double-blind, placebo-controlled trial, enoxaparin (40 mg once daily) did not improve the chance of a live birth in nonthrombophilic women with unexplained recurrent miscarriage. This trial is registered at www.ClinicalTrials.gov as #NCT00740545 and the French National Health and Drug Safety Agency (EudraCT #2006-003350-18).
在许多医疗中心，对患有不明原因复发性流产的女性，无论其是否存在遗传性易栓症，给予抗血栓药物治疗都是常见的做法。尽管阿司匹林与安慰剂相比的益处尚未得到明确证实，但关于低分子量肝素作用的双盲安慰剂对照试验仍属欠缺。我们招募了258名有不明原因复发性流产病史（妊娠15周前连续≥2次流产）且血栓形成倾向检查结果为阴性的孕妇。她们被随机分配，每天皮下注射一次40毫克依诺肝素或安慰剂，直至妊娠35周。在意向性分析中，我们纳入了256名女性（平均年龄32岁，≥3次流产：72%；平均停经孕周39天）；接受依诺肝素治疗的138名女性中，66.6%活产，而接受安慰剂治疗的118名女性中这一比例为72.9%。绝对差异为-6%（95%CI，-17.1至5.1），排除依诺肝素使活产率增加10%的情况（P = 0.34）。在这项首个随机、双盲、安慰剂对照试验中，依诺肝素（每日一次40毫克）并未提高非血栓形成倾向的不明原因复发性流产女性的活产几率。该试验已在www.ClinicalTrials.gov上注册，编号为#NCT00740545，同时也在法国国家卫生与药品安全局注册（EudraCT编号#2006-003350-18）。
