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山东大学学报 (医学版) ›› 2021, Vol. 59 ›› Issue (8): 14-19.doi: 10.6040/j.issn.1671-7554.0.2021.0825

• 生殖免疫的基础与临床研究进展专题 • 上一篇    下一篇

抗凝药物在反复不良妊娠治疗中的应用进展

张建平,罗莺儿   

  1. 中山大学孙逸仙纪念医院围产专科, 广东 广州 510120
  • 发布日期:2021-09-16
  • 通讯作者: 张建平. E-mail:zjp2570@126.com
  • 基金资助:
    国家重点研发计划(2019YFA0801403)

Application progress of anticoagulant drugs in the treatment of recurrent adverse pregnancy

ZHANG Jianping, LUO Yinger   

  1. Department of Obstetrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, China
  • Published:2021-09-16

摘要: 不良妊娠主要包括自然流产、胎儿生长受限、子痫前期、早产以及羊水过少等。抗磷脂抗体综合征以及其他血栓前状态均可导致机体病理性血液高凝状态,引起以上各种妊娠并发症。抗凝药物以及抗血小板药物不仅可以抗凝,改善胎盘血流,还存在抗炎、抑制补体等调节滋养细胞功能的作用。因此,根据病因采取单独或联合的抗凝或抗血小板药物,在反复不良妊娠患者中应用广泛。论文对抗凝药物在反复不良妊娠中的应用进展进行综述。

关键词: 抗凝, 抗血小板, 不良妊娠, 胎盘介导, 妊娠并发症

Abstract: Adverse pregnancy includes spontaneous abortion, fetal growth restriction, preeclampsia, premature delivery, oligohydramnios, and so on. Antiphospholipid antibody syndrome and other prethrombotic states can lead to the bodys pathological hypercoagulable state, causing the above-mentioned complications. Anticoagulant and antiplatelet drugs can not only anticoagulate and improve placental blood flow, but also have anti-inflammatory and complement inhibition effects to regulate the function of trophoblasts. Therefore, single or combined anticoagulant or antiplatelet drugs are widely used in patients with recurrent adverse pregnancy. This article will review the application progress of anticoagulant drugs in recurrent adverse pregnancy.

Key words: Anticoagulant, Antiplatelet, Adverse pregnancy, Placenta-mediated, Pregnancy complications

中图分类号: 

  • R714.2
[1] 杨小风, 张颖, 刘芳, 等. 血栓前状态与复发性流产[J]. 中国医刊, 2020, 55(3): 248-251.
[2] 王统菲, 贺立颖, 刘志兰, 等. 重视复发性流产患者的血栓前状态诊断[J]. 妇产与遗传(电子版), 2015, 5(3): 37-43.
[3] 游文强, 杨孜. 抗磷脂综合征合并妊娠及产科并发症的预防及处理[J]. 中国计划生育和妇产科, 2020, 12(5): 9-13.
[4] Schreiber K, Sciascia S, Philip G de Groot, et al. Antiphospholipid syndrome[J]. Nat Rev Dis Primers, 2018, 4: 17103. doi: 10.1038/nrdp.2017.103.
[5] Arslan E, Branch DW. Antiphospholipid syndrome: diagnosis and management in the obstetric patient[J]. Best Pract Res Clin Obstet Gynaecol, 2020, 64: 31-40. doi: 10.1016/j.bpobgyn.2019.10.001.
[6] Xi F, Cai Y, Lv M, et al. Anticardiolipin positivity is highly associated with intrauterine growth restriction in women with antiphospholipid syndrome[J]. Clin Appl Thromb Hemost, 2020, 26: 1-7. doi: 10.1177/1076029620974455.
[7] 杜向阳, 何丽梅, 龚波. 血栓前状态与流产的相关性研究[J]. 血栓与止血学, 2020, 26(6): 911-912. DU Xiangyang, HE Limei, GONG Bo. Correlation between prethrombotic state and miscarriage[J]. Chinese Journal of Thrombosis and Hemostasis, 2020, 26(6): 911-912.
[8] Simcox LE, Ormesher L, Tower C, et al. Thrombophilia and pregnancy complications[J]. Int J Mol Sc, 2015, 16(12): 28418-28.
[9] Satta R, Biondi G. Antiphospholipid syndrome and pregnancy[J]. G Ital Dermatol Venereol, 2019, 154(3): 277-285.
[10] Gojnic MG, Dugalic SV, Stefanovic AO, et al. Combined hereditary thrombophilias are responsible for poor placental vascularization development and low molecular weight heparins(LMWH)prevent adverse pregnancy outcomes in these patients[J]. J Matern Fetal Neonatal Med, 2020, 18: 1-8. doi: 10.1080/14767058.2020.1849116.
[11] Groom KM, McCowan LM, Mackay LK, et al. Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction in women with a history: a randomized trial[J]. Am J Obstet Gynecol, 2017, 216(3): 296.
[12] Areia AL, Fonseca E, Areia M, et al. Low-molecular-weight heparin plus aspirin versus aspirin alone in pregnant women with hereditary thrombophilia to improve live birth rate: meta-analysis of randomized controlled trials[J]. Arch Gynecol Obstet, 2016, 293(1): 81-86.
[13] 平昀鹭, 赵小萱, 冯晓玲, 等. 血栓前状态致复发性流产的中西医治疗研究进展[J]. 中医药学报, 2020, 48(10): 64-68.
[14] 武倩文, 马翔, 王嫱. 体外受精-胚胎移植合并抗磷脂抗体阳性诊治进展[J]. 国际生殖健康/计划生育杂志, 2020, 39(5): 407-410. WU Qianwen, MA Xiang, WANG Qiang. Diagnosis and treatment of positive antiphospholipid antibodies in in vitro fertilization and embryo transfer patients[J]. Journal of International Reproductive Health/Family Planning, 2020, 39(5): 407-410.
[15] 季顺东. 血栓形成机制及抗凝药物的药理特点[J]. 中国计划生育和妇产科, 2021, 13(3): 25-28.
[16] 孙思, 赵爱民. 复发性流产常用抗凝及抗血小板药物妊娠期暴露的安全性[J]. 上海交通大学学报(医学版), 2020, 40(3): 402-407. SUN Si, ZHAO Aimin. Safety of anticoagulants and antiplatelet drugs in patients with recurrent spontaneous abortion during pregnancy[J]. Journal of Shanghai Jiaotong University(Medical Science), 2020, 40(3): 402-407.
[17] 蒋维贞. 子痫前期抗凝治疗的研究进展[J]. 实用妇产科杂志, 2019, 35(12): 910-914.
[18] Zhang K, Wang E, Li Y, et al. Role of low-molecular-weight heparin in altering uterine artery blood flow in recurrent spontaneous abortion: a prospective study[J]. J Int Med Res, 2020, 48(8): 30006052094555. doi:10.1177/0300060520945558.
[19] Schindewolf M, Recke A, Zillikens DD, et al. Nadroparin carries a potentially high risk of inducing cutaneous delayed-type hypersensitivity responses[J]. Contact Dermatitis, 2017, 77(1): 35-41.
[20] Shaaban OM, Abbas AM, Zahran KM, et al. Low-Molecular-Weight heparin for the treatment of unexplained recurrent miscarriage with negative antiphospholipid antibodies: a randomized controlled trial[J]. Clin Appl Thromb Hemost, 2017, 23(6): 567-572.
[21] Haruta S, Maruta K, Nakajima Y, et al. Use of fondaparinux for thromboprophylaxis in an unfractionated heparin-intolerant pregnant woman with thrombotic predisposition[J]. Journal of Obstetrics and Gynaecology Research, 2017, 43(5): 943-945.
[22] Schindewolf M, Steindl J, Beyer-Westendorf J, et al. Use of fondaparinux off-label or approved anticoagulants for management of heparin-induced thrombocytopenia[J]. J Obstet Gynaecol Res, 2017, 43(5): 943-945.
[23] Groom KM, David AL. The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction[J]. Am J Obstet Gynecol, 2018, 218(2): 829-840.
[24] Bruno V, Svensson-Arvelund J, Rubér M, et al. Effects of low molecular weight heparin on the polarization and cytokine profile of macrophages and T helper cells in vitro[J]. Sci Rep, 2018, 8(1): 4166.
[25] Rasmark Roepke E, Bruno V, Nedstrand E, et al. Low-molecular-weight-heparin increases Th1- and Th17-associated chemokine levels during pregnancy in women with unexplained recurrent pregnancy loss: a randomised controlled trial[J]. Sci Rep, 2019, 9(1): 12314.
[26] Yoshihara H, Sugiura-Ogasawara M, Kitaori T, Danaparoid is effective and safe for patients with obstetric antiphospholipid syndrome[J]. Mod Rheumatol, 2020, 30(2): 332-337.
[27] Li X, Deng X, Duan H, et al. Clinical features associated with pregnancy outcomes in women with positive antiphospholipid antibodies and previous adverse pregnancy outcomes: a real-world prospective study[J]. Clin Rheumatol, 2021, 40(1): 193-204.
[28] Jacobson B, Rambiritch V, Paek D, et al. Safety and efficacy of enoxaparin in pregnancy: a systematic review and meta-analysis[J]. Adv Ther, 2020, 37(1): 27-40.
[29] Areia AL, Fonseca E, Areia M, et al. Low-molecular-weight heparin plus aspirin versus aspirin alone in pregnant women with hereditary thrombophilia to improve live birth rate: meta-analysis of randomized controlled trials[J]. Arch Gynecol Obstet, 2016, 293(1): 81-86.
[30] Chaemsaithong P, Cuenca-Gomez D, Plana MN, et al. Does low-dose aspirin initiated before 11 weeks gestation reduce the rate of preeclampsia?[J]. Am J Obstet Gynecol, 2020, 222(5): 437-450.
[31] Barlow A, Barlow B, Reinaker T. Potential role of direct oral anticoagulants in the management of heparin-induced thrombocytopenia[J]. Pharmacotherapy, 2019, 39(8): 837-853.
[32] Kanatani Y, Miyagawa F, Ogawa K, et al. Parallel changes in serum thymus and activation-regulated chemokine levels in response to flare-ups in drug-induced hypersensitivity syndrome[J]. J Dermatol, 2020, 47(11): 417-419.
[33] Mazarico E, Molinet-Coll C, Martinez-Portilla RJ, et al. Heparin therapy in placental insufficiency: systematic review and meta-analysis[J]. Acta Obstet Gynecol Scand, 2020, 99(2): 167-174.
[34] Zhu Q, Zhou S, Liu Z. Fondaparinux and direct oral anticoagulants: promising anticoagulant for management of heparin-induced thrombocytopenia[J]. J Am Coll Cardiol, 2018, 71(15): 1710.
[35] Aynıoglu O, Isik H, Sahbaz A, et al. Does anticoagulant therapy improve adverse pregnancy outcomes in patients with history of recurrent pregnancy loss?[J]. Ginekol Pol, 2016, 87(8): 585-591.
[36] Aracic N, Roje D, Jakus IA, et al. The impact of inherited thrombophilia types and low molecular weight heparin treatment on pregnancy complications in women with previous adverse outcome[J]. Yonsei Med J, 2016, 57(5): 1230-1235.
[37] Mekinian A, Vicaut E, Cohen J, et al. Hydroxychloroquine to obtain pregnancy without adverse obstetrical events in primary antiphospholipid syndrome: French phase Ⅱ multicenter randomized trial, HYDROSAPL[J]. Gynecol Obstet Fertil Senol, 2018, 46(7-8): 598-604.
[38] Hamulyák EN, Scheres LJ, Marijnen MC, et al. Aspirin or heparin or both for improving pregnancy outcomes in women with persistent antiphospholipid antibodies and recurrent pregnancy loss[J]. Cochrane Database Syst Rev, 2020, 5(5): CD012852.
[39] de Jong PG, Kaandorp S, Di Nisio M, et al. Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia[J]. Cochrane Database Syst Rev, 2014, 2014(7): CD004734.
[40] 欧华, 郁琦. 阿司匹林、泼尼松及爱乐维联合用药在治疗不明原因早期复发性自然流产中的效果观察[J]. 中华医学杂志, 2017, 97(41): 3250-3254. OU Hua, YU Qi. Effects of combination therapy with aspirin, prednisone, and Elevit in patients with unexplained recurrent early pregnancy loss[J]. National Medical Journal of China, 2017, 97(41): 3250-3254.
[41] Nawathe A, David AL. David, Prophylaxis and treatment of foetal growth restriction[J]. Best Pract Res Clin Obstet Gynaecol, 2018, 49: 66-78. doi:10.1016/j.bpobgyn.2018.02.007.
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