Research and Therapeutic Advances in Recurrent Spontaneous Abortion Complicated with Hereditary Thrombophilia

doi:10.12280/gjfckx.20251278

Abstract

Abstract:

Recurrent spontaneous abortion (RSA) combined with hereditary thrombophilia is a significant cause of adverse pregnancy outcomes. Hereditary thrombophilia mainly involves deficiencies of anticoagulant proteins (protein C, protein S, antithrombin Ⅲ), factor Ⅴ Leiden (FⅤL) mutation, prothrombin G20210A gene mutation (PGM), methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, and plasminogen activator inhibitor-1 (PAI-1) 5G/4G gene mutations. Western medical treatment primarily employs low molecular weight heparin (LMWH) anticoagulation to improve hypercoagulability and promote placental blood perfusion, thereby reducing abortion risk. However, there is currently a lack of high-quality evidence-based medical data supporting its efficacy, and its clinical application remains controversial. Traditional Chinese Medicine (TCM) follows the pathogenesis of "kidney deficiency and blood stagnation", adopting the therapeutic principle of "tonifying kidney and activating blood circulation". Under holistic syndrome differentiation, TCM seeks etiological treatment, using classic formulas such as Shoutai Pill to tonify kidney and stabilize the Chong Mai, combined with low-dose promoting blood circulation and removing blood stasis drugs like Salvia miltiorrhiza and Angelica sinensis. Clinical practice has demonstrated considerable efficacy. In recent years, integrated Chinese-Western medicine therapy has shown favorable synergistic effects, improving pregnancy success rate while reducing the dosage and adverse effects of Western medications, thereby providing novel therapeutic strategies for RSA complicated with hereditary thrombophilia.

Key words: Abortion, habitual, Hereditary thrombophilia, Polymorphism, genetic, Heparin, low-molecular-weight, Kidney deficiency and blood stagnation, Tonifying kidney and activating blood circulation

WANG Cheng-xia, ZHAO Jia-run, ZHENG Shu-chang, WANG Yi-di, HE Jun-qin. Research and Therapeutic Advances in Recurrent Spontaneous Abortion Complicated with Hereditary Thrombophilia[J]. Journal of International Obstetrics and Gynecology, 2026, 53(2): 159-164.

References 42

[1]	中华医学会妇产科学分会产科学组, 复发性流产诊治专家共识编写组. 复发性流产诊治专家共识(2022)[J]. 中华妇产科杂志, 2022, 57(9):653-667. doi: 10.3760/cma.j.cn112141-20220421-00259.
[2]	周凤高, 苏瑜, 王雪娟, 等. PAI-1基因杂合突变合并MTHFR基因纯合突变致遗传性易栓症1例分析[J]. 重庆医学, 2024, 53(8):1278-1280. doi: 10.3969/j.issn.1671-8348.2024.08.030.
[3]	广东省精准医学会血液分会出凝血青年专委会, 广东省易栓症多学科专家共识编写组. 广东省易栓症诊治多学科专家共识[J]. 岭南现代临床外科, 2023, 23(5):367-378. doi: 10.3969/j.issn.1009-976X.2023.05.001.
[4]	朱铁楠, 赵永强, 丁秋兰, 等. 汉族人群蛋白 C、蛋白S和抗凝血酶活性水平及活性缺乏发生率的研究[J]. 中华血液学杂志, 2012, 33(2):127-130. doi: 10.3760/cma.j.issn.0253-2727.2012.02.015.
[5]	刘志兰, 康晓敏, 张晓欣, 等. 复发性自然流产1101例病因分析[J]. 上海交通大学学报(医学版) 2015, 35(3):396-401. doi: 11.3969/j.issn.1674-8115.2015.03.018.
[6]	Delis M, Emmanouilidou-Fotoulaki E, Chatzakis C, et al. Inherited thrombophilias and stillbirth: a systematic review and meta- analysis[J]. Arch Gynecol Obstet, 2025, 312(1):37-50. doi:10.1007/s00404-025-07989-60. pmid: 40087172
[7]	颜伟, 朱韵怡, 吴效科, 等. 亚甲基四氢叶酸还原酶(MTHFR)基因多态性与复发性流产相关性的研究进展[J]. 中国计划生育学杂志, 2025, 33(1):242-248. doi: 10.3969/j.issn.1004-8189.2025.01.049.
[8]	何婷, 王英兰, 陆成娴. PAI-1基因多态性与不明原因复发性流产易感性关联的Meta分析[J]. 中国计划生育和妇产科, 2025, 17(4):69-74. doi: 10.3969/j.issn.1674-4020.2025.04.16.
[9]	Hussein A, Solouki A, Pilehvari N, et al. "Unraveling the Clot-Miscarriage Nexus: Mechanisms, Management, and Future Directions in Thrombosis-Related Recurrent Pregnancy Loss"[J]. Clin Appl Thromb Hemost, 2025, 31:10760296251339421. doi:10.1177/10760296251339421.
[10]	Al-Sanabra OM, Al-Eitan LN, Jarrar Y, et al. Novel Association of Thrombophilic PROS1, PROC and CPB2 Genes Polymorphisms with Recurrent Spontaneous Miscarriage Women in Jordan[J]. Clin Appl Thromb Hemost, 2025, 31:1076029625133378. doi: 10.1177/107602962513337833.
[11]	Liu X, Chen Y, Ye C, et al. Hereditary thrombophilia and recurrent pregnancy loss: a systematic review and meta-analysis[J]. Hum Reprod, 2021, 36(5):1213-1229. doi: 10.1093/humrep/deab010.
[12]	Xu Z, Zhang Y, Liu W, et al. Polymorphisms of F2, PROC, PROZ, and F13A1 genes are associated with recurrent spontaneous abortion in Chinese han women[J]. Clin Appl Thromb Hemost, 2018, 24(6):894-900. doi: 10.1177/1076029617750487.
[13]	James AH, Bates SM, Bauer KA, et al. Management of hereditary antithrombin deficiency in pregnancy[J]. Thromb Res, 2017, 157:41-45. doi: 10.1016/j.thromres.2017.05.017. pmid: 28689083
[14]	吴剑锋. 复发性自然流产患者血浆D-二聚体、抗凝血酶Ⅲ和蛋白C检测的临床意义[J]. 现代检验医学杂志, 2018, 33(4):112-114. doi: 10.3969/j.issn.1671-7414.2018.04.030.
[15]	杨旭虎, 徐伍, 刘建成, 等. 易栓症分子遗传学研究进展[J]. 陕西医学杂志, 2023, 52(10):1442-1445. doi: 10.3969/j.issn.1000-7377.2023.10.037.
[16]	国家妇幼健康研究会生殖免疫学专业委员会专家共识编写组. 复发性流产合并血栓前状态诊治中国专家共识[J]. 中华生殖与避孕杂志, 2021, 41(10):861-875. doi: 10.3760/cma.j.cn101441-20210715-00310.
[17]	Kammawal Y. Persistent Anticoagulation and Severe Upper Gastrointestinal Bleeding in a Patient With Factor V Leiden: A Case of the Warfarin Reservoir Phenomenon[J]. Cureus, 2025, 17(9):e91638. doi: 10.7759/cureus.91638.
[18]	Sedano-Balbas S, Lyons M, Cleary B, et al. Acquired activated protein C resistance, thrombophilia and adverse pregnancy outcomes: A study performed in an Irish cohort of pregnant women[J]. J Pregnancy, 2011, 2011(1): 232840. doi:10.1155/2011/232840.
[19]	Ahmed Abd Elhameed Z, Shaaban OM, Abd Elazeem HG, et al. Role of Prothrombin and Methylenetetrahydrofolate Reductase Gene Polymorphisms as well as Thrombophilia Markers, as Risk Factors for Unexplained Recurrent Miscarriage: A Case-Control Study[J]. Int J Fertil Steril, 2025, 19(1):36-43. doi: 10.22074/ijfs.2023.1986225.1418. pmid: 39827389
[20]	Wen Y, He H, Zhao K. Thrombophilic gene polymorphisms and recurrent pregnancy loss: a systematic review and meta-analysis[J]. J Assist Reprod Genet, 2023, 40(7):1533-1558. doi: 10.1007/s10815-023-02823-x.
[21]	薛慧琴, 蒋劲嵩, 武坚锐, 等. 血栓前状态基因多态性与复发性流产的相关性[J]. 医药论坛杂志, 2023, 44(16):1-5.
[22]	Maghsudlu M, Noroozi Z, Zokaei E, et al. Systematic review and meta-analysis of association between plasminogen activator inhibitor-1 4G/5G polymorphism and recurrent pregnancy loss: an update[J]. Thromb J, 2024, 22(1):44. doi: 10.1186/s12959-024-00612-9. pmid: 38807142
[23]	Scarrone M, Salmeri N, Buzzaccarini G, et al. Low-molecular-weight heparin in the prevention of unexplained recurrent miscarriage: a systematic review and meta-analysis[J]. Sci Rep, 2024, 14(1):14168. doi: 10.1038/s41598-024-62949-5. pmid: 38898143
[24]	Chen M, Chen YT, Chen CM, et al. Benefits and risks of low molecular weight heparin use on reproductive outcomes: A retrospective cohort study[J]. Taiwan J Obstet Gynecol, 2022, 61(5):812-817. doi: 10.1016/j.tjog.2022.05.015. pmid: 36088049
[25]	Grandone E, Tiscia GL, Mastroianno M, et al. Findings from a multicentre, observational study on reproductive outcomes in women with unexplained recurrent pregnancy loss: the OTTILIA registry[J]. Hum Reprod, 2021, 36(8):2083-2090. doi: 10.1093/humrep/deab153.
[26]	Chen Y, Wang T, Liu X, et al. Low molecular weight heparin and pregnancy outcomes in women with inherited thrombophilia: a systematic review and meta-analysis[J]. J Obstet Gynaecol Res, 2022, 48(8):2134-2150. doi: 10.1111/jog.15319.
[27]	Maglic D, Mandic-Markovic V, Mikovic Z, et al. Impact of Inherited Thrombophilia on Pregnancy Complications and the Role of Low-Molecular-Weight Heparin Therapy: A Case-Control Study[J]. Medicina(Kaunas), 2025, 61(7):1131. doi: 10.3390/medicina61071131.
[28]	Quenby S, Booth K, Hiller L, et al. Heparin for women with recurrent miscarriage and inherited thrombophilia (ALIFE2): an international open-label, randomised controlled trial[J]. Lancet, 2023, 402(10395):54-61. doi: 10.1016/S0140-6736(23)00693-1. pmid: 37271152
[29]	中国中西医结合学会活血化瘀专业委员会. 血瘀证中西医结合诊疗共识[J]. 中国中西医结合杂志, 2011, 31(6):839-844.
[30]	党雪, 刘飞祥, 封俨宸, 等. 寿胎丸治疗复发性流产的作用机制研究进展[J]. 中国实验方剂学杂志, 2025, 31(6):283-291. doi: 10.13422/j.cnki.syfjx.20241621.
[31]	姜晓杰, 谈勇. 谈勇教授“通因通用”法治疗复发性流产血栓前状态临证经验[J]. 亚太传统医药, 2024, 20(11):98-102. doi: 10.11954/ytctyy.202411017.
[32]	丘维钰, 高飞霞, 巫海旺, 等. 罗颂平从肾虚血瘀论治复发性流产经验介绍[J]. 新中医, 2018, 50(3):217-220. doi: 10.13457/j.cnki.jncm.2018.03.062.
[33]	马旭, 李淑萍. 李淑萍教授治疗复发性流产血栓前状态的临床经验[J]. 浙江中医药大学学报, 2016, 40(1):44-46. doi: 10.16466/j.issn1005-5509.2016.01.013.
[34]	彭丽, 李佩瑶, 胡小芳. 胡小芳教授治疗易栓症致复发性流产经验浅探[J]. 中国中医药现代远程教育, 2023, 21(8):146-148. doi: 10.3969/j.issn.1672-2779.2023.08.055.
[35]	吴花, 李伟莉. 李伟莉从瘀论治复发性流产血栓前状态[J]. 中医学报, 2020, 35(6):1226-1229. doi: 10.16368/j.issn.1674-8999.2020.06.276.
[36]	倪爽, 李佶. 王大增分阶段辨治复发性流产经验[J]. 上海中医药杂志, 2016, 50(5):17-18. doi: 10.16305/j.1007-1334.2016.05.005.
[37]	王洋, 王春霞, 姜玉婷, 等. 王春霞教授治疗血栓前状态复发性流产临证经验[J]. 中国中医药现代远程教育, 2025, 23(7):62-65. doi: 10.3969/j.issn.1672-2779.2025.07.021.
[38]	章恒端, 林奕岑, 温晓文. 当归芍药保胎散联合低分子肝素钠治疗肾虚血瘀型复发性流产伴血栓前状态临床研究[J]. 新中医, 2024, 56(22):95-100. doi: 10.13457/j.cnki.jncm.2024.22.019.
[39]	付淼, 刘蓬, 田文, 等. 参茸保胎丸联合西医常规治疗用于复发性流产合并血栓前状态患者的疗效及对凝血纤溶系统、血清炎症因子的影响[J]. 中国医院用药评价与分析, 2023, 23(6):682-685. doi: 10.14009/j.issn.1672-2124.2023.06.010.
[40]	李晖, 褚玉霞, 孙红. 加味褚氏安胎方联合常规治疗对肾虚血瘀型血栓前状态致复发性流产患者的临床疗效[J]. 中成药, 2022, 44(10):3170-3174. doi: 10.3969/j.issn.1001-1528.2022.10.015.
[41]	孙利利, 孙自学, 李鹏超. 热敏灸联合西药孕前干预肾虚血瘀型复发性流产血栓前状态疗效观察[J]. 中国针灸, 2025, 45(9):1253-1258. doi: 10.13703/j.0255-2930.20240617-0001.
[42]	姜朵生, 桂雨涵, 严江天, 等. 针药联合对复发性流产患者血栓前状态子宫内膜容受性及妊娠结局的影响[J]. 时珍国医国药, 2023, 34(3):635-638. doi: 10.3969/j.issn.1008-0805.2023.03.33.