探讨复发性流产(RSA)后再次妊娠早孕期孕妇血栓标志物，并评估低分子肝素(LMWH)干预对血栓标志物水平异常RSA孕妇妊娠结局的影响。

选择2018年1月至2019年10月在苏州大学附属第二医院妇产科就诊的174例RSA早孕期孕妇(孕龄为7~10孕周)为研究对象，并纳入研究组。将同期在本院就诊并定期进行产前检查的78例健康孕妇纳入对照组。研究组174例孕妇中，血栓5项标志物[血栓弹力图(TEG)、抗凝血酶(AT)-Ⅲ、同型半胱氨酸(Hcy)、血小板最大聚集率(MAR)、D-二聚体(DD)]任意一项升高为139例，根据是否采取LMWH干预治疗，将其分为干预亚组(n＝91，采取LMWH干预治疗措施)和未干预亚组(n＝48，未采取LMWH干预治疗措施)。采用回顾性分析法，对研究组与对照组孕妇年龄、人体质量指数(BMI)和孕龄等一般临床资料进行分析，并对其血栓5项标志物水平进行比较。绘制Hcy、TEG最大振幅(MA)值和MAR诊断RSA孕妇血栓前状态(PTS)受试者工作特征(ROC)曲线，并计算ROC曲线下面积(ROC-AUC)，根据约登指数最大原则，确定Hcy、MA值和MAR诊断RSA孕妇PTS的最佳临界值，并计算其诊断PTS的敏感度、特异度。本研究遵循的程序符合苏州大学附属第二医院伦理委员会规定，并获得该伦理委员会批准(审批文号：JD-LK-2018-030-03)，与所有参与本研究的受试者签署临床研究知情同意书。

①研究组与对照组孕妇年龄、BMI及孕龄比较，差异均无统计学意义(P>0.05)。②研究组和对照组孕妇MA值、Hcy和MAR分别比较[(65.3±5.4) mm vs (62.3±5.2) mm、(8.3±3.2) g/L vs (7.4±1.9) g/L及(73.8±7.7)% vs (69.9±9.3)%]，差异均有统计学意义(t＝5.135、3.512、4.724，P＝0.036、0.012、0.014)。③Hcy、MA值和MAR诊断RSA孕妇PTS的ROC-AUC分别为0.681(95%CI：0.611~0.750，P<0.001)，0.712(95%CI：0.651~0.773，P<0.001)，0.877(95%CI：0.838~0.916，P<0.001)。根据约登指数最大原则，Hcy、MA值和MAR诊断RSA孕妇PTS的最佳临界值分别为7.05 g/L、59.1 mm、70.5%，并且诊断RSA孕妇PTS的敏感度分别为73.3%、80.1%及70.1%，特异度分别为65.2%、55.0%、92.1%。④干预亚组、未干预亚组和对照组孕妇活产率、流产率、妊娠随访率、剖宫产率比较，差异均有统计学意义(P<0.05)。⑤随访期内干预亚组孕妇无一例出现血小板减少、严重变态反应及肝、肾功能受损等情况。

Hcy、MA值、MAR血栓3项标志物，对RSA孕妇的PTS诊断具有一定预警作用。建议对血栓标志物水平异常的RSA患者，应及时采取LMWH治疗措施，对于改善其妊娠结局有一定作用。

To investigate thrombus markers of pregnant women in first trimester with recurrent spontaneous abortion (RSA), and to evaluate treatment effects of low molecular weight heparin (LMWH) on pregnancy outcomes of those with abnormal thrombus markers.

A total of 174 pregnant women in first trimester with RSA history who were admitted into the Department of Gynecology and Obstetrics of the Second Affiliated Hospital of Soochow University from January 2018 to October 2019 were selected into this study (study group). Meanwhile 78 healthy pregnant women in first trimester who underwent prenatal examination in the same hospital were included into control group. Of the 174 pregnant women in study group, 139 cases whose levels of any one in 5 indexes of thrombotic markers [thromboelastography (TEG), antithrombin (AT)-Ⅲ, homocysteine (Hcy), maximum platelet aggregation rate (MAR), and D-dimer (DD)] increased remarkably were divided into intervention subgroup (n=91, treated by LMWH) and non-intervention subgroup (n=48, treated without LMWH) according to whether by LMWH or not. The general clinical data, such as age, body mass index (BMI) and gestational age between study group and control group were retrospectively analyzed, and thrombus markers were compared. The receiver operating characteristics (ROC) curves of different indexes (Hcy, MA of TEG and MAR) to diagnose prethrombotic state (PTS) of pregnant women were drawn, and area under the curve (AUC) was calculated. According to principle of maximum Youden index, the best critical values of different indexes for diagnosing RSA pregnant women with PTS were determined. The procedure followed in this study met the standards formulated by the Ethics Review Committee of Second Affiliated Hospital of Soochow University and has been approved by it (Approval No. JD-LK-2018-030-03). Informed consent was obtained from each participate.

① There were no significant differences in age, BMI and gestational age between study group and control group (P>0.05). ②There were significant difference in MA of TEG value [(65.3±5.4) mm vs (62.3±5.2) mm], Hcy [(8.3±3.2) g/L vs (7.4±1.9) g/L], and MAR [(73.8±7.7)% vs (69.9±9.3)%] between study group and control group (t=5.135, 3.512, 4.724; P=0.036, 0.012, 0.014). ③The AUC of Hcy, MA of TEG value and MAR in diagnosing PTS of RSA gravidae were 0.681 (95%CI: 0.611-0.750, P<0.001), 0.712 (95%CI: 0.651-0.773, P<0.001), 0.877 (95%CI: 0.838-0.916, P<0.001), respectively. According to the principle of maximum Youden index, the best critical value of Hcy, MA of TEG value and MAR in diagnosing RSA pregnant women with PTS were 7.05 g/L, 59.1 mm, and 70.5%, and the sensitivities were 73.3%, 80.1% and 70.1%, and specificities were 65.2%, 55.0%, and 92.1%, respectively. ④There were significant differences in live birth rate, abortion rate, pregnancy follow-up rate and cesarean section rate among intervention group, non-intervention group and control group (P<0.05). ⑤ None of pregnant women in intervention subgroup showed thrombocytopenia, severe allergic reactions, or impaired liver or kidney function during the follow-up period.

Three thrombotic markers, Hcy, MA of TEG value, and MAR, have early warning effects on the diagnosis of PTS of RSA pregnant women. The promotion of LMWH therapy is recommended for RSA re-pregnancy patients with abnormal levels of thrombotic markers, which may improve their pregnancy outcomes.