那曲肝素钙联合阿司匹林治疗复发性流产的效果及对患者血清TSP-1、sflt-1水平影响

doi:10.3760/cma.j.issn.1007-1245.2022.09.024

摘要/Abstract

摘要： 目的　探讨那曲肝素钙联合阿司匹林治疗复发性流产（RSA）的效果及对患者血清血小板反应蛋白-1（TSP-1）、可溶性血管内皮生长因子受体-1（sflt-1）水平的影响。方法　选取2019年1月至2020年1月佳木斯市妇幼保健院收治的RSA患者112例为观察对象，按照随机数字表法分为对照组与观察组，每组56例。对照组年龄（29.36±2.82）岁，流产次数（4.79±0.45）次，孕周（7.64±0.75）周；观察组年龄（29.29±2.80）岁，流产次数（4.77±0.43）次，孕周（7.68±0.77）周。对照组采用阿司匹林治疗，观察组加用那曲肝素钙治疗。比较两组凝血4项［凝血酶原时间（PT）、凝血酶时间（TT）、部分活化凝血酶时间（APTT）、纤维蛋白原（FIB）］与血清TSP-1、sflt-1水平及不良反应、保胎结局。计量资料进行t检验，计数资料用χ²检验。结果　治疗后，观察组PT、TT、APTT长于对照组［（12.46±1.02）s比（11.63±1.05）s、（14.40±1.17）s比（13.25±1.16）s、（29.67±2.12）s比（26.92±2.19）s］，FIB低于对照组［（3.56±0.34）g/L比（4.02±0.35）g/L］，差异均有统计学意义（均P<0.05）；治疗后，观察组血清TSP-1、sflt-1均低于对照组［分别为（0.83±0.07）μg/L比（1.17±0.09）μg/L、（7 512.06±731.65）μg/L比（9 050.79±722.10）μg/L］，差异均有统计学意义（t=33.315、11.201，均P<0.001）；观察组不良反应发生率为12.50%（7/56），与对照组的5.36%（3/56）比较，差异无统计学意义（P>0.05）；观察组保胎成功率为83.93%（47/56），高于对照组的66.07%（37/56），差异有统计学意义（χ²=4.719，P=0.030）。结论　那曲肝素钙联合阿司匹林治疗复发性流产能改善患者的凝血功能，并下调血清TSP-1、sflt-1水平，降低流产率，提高保胎成功率。

关键词: 那曲肝素钙, 阿司匹林, 复发性流产, 血小板反应蛋白-1, 可溶性血管内皮生长因子受体-1, 凝血功能

Abstract: Objective　To investigate the effect of nadroparin calcium combined with aspirin in the treatment of recurrent spontaneous abortion (RSA) and its effect on the levels of serum thrombospondin-1 (TSP-1) and soluble fms-like tyrosine kinase-1 (sflt-1). Methods　A total of 112 patients with RSA admitted to Jiamusi Maternal and Child Health Care Hospital from January 2019 to January 2020 were selected as the observation objects, and were divided into a control group and an observation group according to the random number table method, with 56 cases in each group. The control group were (29.36±2.82) years old, had (4.79±0.45) times abortion, and their gestational age was (7.64±0.75) weeks. The observation group were (29.29±2.80) years old, had (4.77±0.43) times abortion, and their gestational age was (7.68±0.77) weeks. The control group were treated with aspirin, and the observation group with aspirin and nadroparin calcium. The four blood coagulation items [prothrombin time (PT), thrombin time (TT), activated partial thromboplatin time (APTT), and fibrinogen (FIB)], serum levels of TSP-1 and sflt-1, adverse reactions, and pregnancy outcomes were compared between the two groups. The measurement data were analyzed by t test, and the enumeration data by χ² test. Results　After the treatment, the PT, TT, and APTT were longer and the FIB level was lower in the observation group than in the control group [(12.46±1.02) s vs. (11.63±1.05) s, (14.40±1.17) s vs. (13.25±1.16) s, (29.67±2.12) s vs. (26.92±2.19) s, and (3.56±0.34) g/L vs. (4.02±0.35) g/L], with statistical differences between the two groups (all P<0.05). After the treatment, the serum levels of TSP-1 and sflt-1 in the observation group were lower than those in the control group [(0.83±0.07) μg/L vs. (1.17±0.09) μg/L and (7 512.06±731.65) μg/L vs. (9 050.79±722.10) μg/L], with statistical differences between the two groups (t=33.315 and 11.201, both P<0.001). The incidence of adverse reactions was 12.50% (7/56) in the observation group, and was 5.36% (3/56) in the control group, with no statistical difference between the two groups (P>0.05). The success rate of miscarriage protection was 83.93% (47/56) in the observation group, and was 66.07% (37/56) in the control group, with a statistical difference between the two groups (χ²=4.719, P=0.030). Conclusion　Natroparin calcium in the treatment of recurrent abortion can improve the patients' coagulation function, reduce the serum levels of TSP-1 and sflt-1 and the abortion rate, and improve the success rate of miscarriage protection.

Key words: Nadroparin calcium, Aspirin, Recurrent spontaneous abortion, Thrombospondin-1, Soluble fms-like tyrosine kinase-1, Coagulation function

辛秀. 那曲肝素钙联合阿司匹林治疗复发性流产的效果及对患者血清TSP-1、sflt-1水平影响[J]. 国际医药卫生导报, 2022, 28(9): 1288-1292.

Xin Xiu.

Effect of nadroparin calcium combined with aspirin in treatment of recurrent spontaneous abortion and its influence on patients' serum levels of TSP-1 and sflt-1 [J]. International Medicine and Health Guidance News, 2022, 28(9): 1288-1292.

参考文献

[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.DOI:10.3969/j.issn.1008-1070. 2020.03.006.

[2] 汪希鹏.复发性流产与反复种植失败的病因和治疗新观点[J].中华妇产科杂志,2019,54(12):793-796.DOI:10.3760/cma.j.issn.0529-567x.2019.12.001.

[3] Kaymaz E, Gun BD, Genc GC, et al. May the morphological findings in the first-trimester abortion materials be indicative of inherited thrombophilia?[J]J Obstet Gynaecol Res, 2020,46(11):2261-2271. DOI: 10.1111/jog.14419.

[4] 刘梅梅,王珊,李肖肖,等.血小板反应蛋白-1等血管相关因子在复发性流产中的表达及临床研究[J].中华生殖与避孕杂志,2018,38(1):39-43.DOI:10.3760/cma.j.issn.2096-2916.2 018.01.009.

[5] 中华医学会妇产科学分会产科学组.复发性流产诊治的专家共识[J].中华妇产科杂志,2016,(1):3-9.DOI:10.3760/cma.j.issn.0529-567x.2016.01.002.

[6] Turocy JM, Rackow BW. Uterine factor in recurrent pregnancy loss[J]. Semin Perinatol, 2019,43(2):74-79. DOI: 10.1053/j.semperi.2018.12.003.

[7] 吴胜男,金莉萍.复发性流产的内分泌因素[J].中国实用妇科与产科杂志,2020,36(11):1069-1072.DOI:10.19538/j.fk2020110110.

[8] Ratovoson R, Kunkel A, Rakotovao JP, et al. Frequency, risk factors, and complications of induced abortion in ten districts of Madagascar: results from a cross-sectional household survey[J]. BMC Womens Health, 2020,20(1):96. DOI: 10.1186/s12905-020-00962-2.

[9] 李昀晖,徐畅,张文,等.凝血指标在病理性妊娠诊治中的应用价值[J].临床输血与检验,2021,23(1):127-131.DOI:10.3969/j.issn.1671-2587.2021.01.032.

[10] 肖金生,王厚照.8项凝血相关指标与复发性流产的相关性研究[J].国际医药卫生导报,2018,24(7):1092-1094.DOI:10.3760/cma.j.issn.1007-1245.2018.07.043.

[11] Emery SP, Lopa S, Waters JH. Impact of intrauterine transfusion on fetal coagulation physiology by thromboelastography[J]. Prenat Diagn, 2020,40(5):585-589. DOI: 10.1002/pd.5651.

[12] 钟伟芬,晏红锦,杨丽君,等.低分子肝素治疗复发性流产患者凝血及血液流变学状态观察[J].中国计划生育和妇产科,2020,12(5):29-32.DOI:10.3969/j.issn.1674-4020. 2020.05.07.

[13] 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.DOI:10.3969/j.issn.1674-8115.2020.03.021.

[14] Devall AJ, Coomarasamy A. Sporadic pregnancy loss and recurrent miscarriage[J]. Best Pract Res Clin Obstet Gynaecol, 2020,69(1):30-39. DOI: 10.1016/j.bpobgyn. 2020.09.002.

[15] 吴芳,王素梅,葛莉萍.抗凝药物对妊娠期高血压疾病母胎结局的影响[J].中国临床新医学,2018,11(7):635-639.DOI:10.3969/j.issn.1674-3806.2018.07.03.

[16] von Tempelhoff GF, Schelkunov O, Demirhan A, et al. Thrombelastometric results and platelet function during pregnancy in women receiving low molecular weight heparin with a history of recurrent/late abortion- aretrospective analysis[J]. Clin Hemorheol Microcirc, 2015,61(1):99-110. DOI: 10.3233/CH-151949.

[17] 马寅芙,刘磊,王起来,等.APS复发性流产患者血小板的活化及其对内皮细胞的影响[J].中国免疫学杂志,2019,35(19):2396-2399.DOI:10.3969/j.issn.1000-484X.2019.19.017.

[18] 宗璐,骆丽华,栾红兵,等.复发性流产患者血液学指标检测分析[J].皖南医学院学报,2019,38(6):531-534.DOI:10.3969/j.issn.1002-0217.2019.06.006.

[19] Boldeanu L, Dijmărescu AL, Radu M, et al. The role of mediating factors involved in angiogenesis during implantation[J]. Rom J Morphol Embryol, 2020,61(3):665-672. DOI: 10.47162/RJME.61.3.04.

[20] 王媛中,李元琪,李伟莉.母胎界面血管生成调控因子与复发性流产的研究[J].长春中医药大学学报,2017,33(6):979-983.DOI:10.13463/j.cnki.cczyy.2017.06.040.

[21] 陈汉华.血管内皮生长因子和妊娠相关蛋白A的表达与复发性流产的相关性分析[J].中国性科学,2018,27(12):81-84.DOI:10.3969/j.issn.1672-1993.2018.12.024.

[22] Ganguly R, Khanal S, Mathias A, et al. TSP-1 (thrombospondin-1) deficiency protects ApoE-/- mice against leptin-induced atherosclerosis[J]. Arterioscler Thromb Vasc Biol, 2021,41(2):e112-e127. DOI: 10.1161/ATVBAHA.120.314962.

[23] 冯六连,李儒佑.血小板反应蛋白-1在复发性流产患者绒毛膜组织中的表达及其价值探讨[J].现代中西医结合杂志,2019,28(14):1533-1536.DOI:10.3969/j.issn.1008-8849. 2019.14.013.

[24] 刘炜,徐聆峰,谭宗建.原因不明复发性流产与sFlt-1的相关性及其临床意义分析[J].贵州医药,2019,43(10):1533-1535.DOI:10.3969/j.issn.1000-744X.2019.10.006.

[25] 刘慧,王文珠,张璐,等.miR-200、 miR-155及血管新生因子与复发性流产的相关性分析[J].实用预防医学,2020,27(11):1341-1344.DOI:10.3969/j.issn.1006-3110. 2020. 11.015.

[26] 李侠,肖维.TSP-1、sflt-1在复发性流产患者血清及绒毛膜中的表达及临床意义[J].中国优生与遗传杂志,2019,27(11):1344-1346,封2. DOI:10.13404/j.cnki.cjbhh.2019. 11.022.

[27] Ali SA, Moiz B, Sheikh L. Association of Factor V Leiden G1691A and Prothrombin gene G20210A mutations with adverse pregnancy outcomes[J]. J Pak Med Assoc, 2021,71(7):1780-1784. DOI: 10.47391/JPMA.1377.

[28] 杨舒奇,黄明莉,黄凌佳,等.血管内皮生长因子家族在妇产科若干疾病中的研究进展[J].中国生育健康杂志,2020,31(2):184-186,190.DOI:10.3969/j.issn.1671-878X. 2020.02.021.

[29] Shamshirsaz AA, Fox KA, Erfani H, et al. Trimester-specific thromboelastic values and coagulation activation markers in pregnancy compared across trimesters and compared to the nonpregnant state[J]. Int J Lab Hematol, 2021,43(5):1216-1224. DOI: 10.1111/ijlh.13472.

[30] 闫媛,牛芳林,王迓君,等.L-精氨酸对人血管内皮细胞的功能的影响[J].中国病理生理杂志,2021,37(6):1011-1018.DOI:10.3969/j.issn.1000-4718.2021.06.007.