akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347/ob.gyn.rep.2021.244akusherstvo-1061Research ArticleEVENTSСОБЫТИЯAdvisory Board conclusion following the discussion "Controversial issues of low molecular weight heparins use in obstetrics"Заключение Экспертного Совета по итогам обсуждения темы «Дискуссионные вопросы применения низкомолекулярных гепаринов в акушерстве»РедакционнаястатьяEditorialArticle202107092021154461469Copyright © Editorial a., 20212021Редакционная с.Editorial a.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gynecology.su/jour/article/view/1061

Antithrombotic therapy is often used during pregnancy for the treatment and prevention of venous thromboembolism, systemic embolism in patients with heart valve prostheses, for prevention of foetal loss in patients with antiphospholipid syndrome, placenta-mediated complications. In common, low molecular weight heparins (LMWHs) have largely replaced unfractionated heparin as the anticoagulant. However, in case of placenta-mediated complications it has off-label status. The effectiveness and safety of the LMWHs in pregnant women at an increased risk of placenta-mediated complications is discussed in this review. LMWH is effective, safety, easy to administer and associated with a low incidence of foetal and maternal complications.

Антитромботическая терапия активно используется у беременных для лечения и профилактики венозных тромбоэмболических осложнений, у пациенток с искусственными клапанами, для профилактики потери плода у пациенток с антифосфолипидным синдромом, при плацента-ассоциированных осложнениях. В большинстве случаев нефракционированный гепарин стал наиболее часто используемым антикоагулянтом; в то же время в случае плацента-ассоциированных осложнений он используется вне одобренных показаний. В данной публикации обсуждается эффективность и безопасность использования низкомолекулярных гепаринов (НМГ) при плацента-ассоциированных осложнениях. НМГ эффективны, имеют благоприятный профиль безопасности, просты в использовании и ассоциированы с низкой частотой осложнений как у матери, так и плода.

беременностьплацента-ассоциированные осложнениянизкомолекулярные гепариныpregnancyplacenta-mediated complicationslow-molecular weight heparinsReferencesCartwright J.E., Fraser R., Leslie K. et al. Remodelling at the maternal-fetal interface: relevance to human pregnancy disorders. Reproduction. 2010;140(6):803-13. https://doi.org/10.1530/REP-10-0294.Cartwright J.E., Fraser R., Leslie K. et al. Remodelling at the maternal-fetal interface: relevance to human pregnancy disorders. Reproduction. 2010;140(6):803-13. https://doi.org/10.1530/REP-10-0294.Helmo F.R., Lopes A.M., Carneiro A.C. et al. Angiogenic and antiangiogenic factors in preeclampsia. Pathol Res Pract. 2018;214(1):7-14. https://doi.org/10.1016/j.prp.2017.10.021.Helmo F.R., Lopes A.M., Carneiro A.C. et al. Angiogenic and antiangiogenic factors in preeclampsia. Pathol Res Pract. 2018;214(1):7-14. https://doi.org/10.1016/j.prp.2017.10.021.Yinon Y., Ben Meir E., Margolis L. et al. Low molecular weight heparin therapy during pregnancy is associated with elevated circulatory levels of placental growth factor. Placenta. 2015;36(2):121-4. https://doi.org/10.1016/j.placenta.2014.12.008.Yinon Y., Ben Meir E., Margolis L. et al. Low molecular weight heparin therapy during pregnancy is associated with elevated circulatory levels of placental growth factor. Placenta. 2015;36(2):121-4. https://doi.org/10.1016/j.placenta.2014.12.008.Rodger M.A., Gris J.-C., de Vries J.I.P. et al; Low-Molecular-Weight Heparin for Placenta-Mediated Pregnancy Complications Study Group. Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials. Lancet. 2016;388(10060):2629-41. https://doi.org/10.1016/S0140-6736(16)31139-4.Rodger M.A., Gris J.-C., de Vries J.I.P. et al; Low-Molecular-Weight Heparin for Placenta-Mediated Pregnancy Complications Study Group. Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials. Lancet. 2016;388(10060):2629-41. https://doi.org/10.1016/S0140-6736(16)31139-4.Cho N.H., Shaw J.E., Karuranga S. et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271-81. https://doi.org/10.1016/j.diabres.2018.02.023.Cho N.H., Shaw J.E., Karuranga S. et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271-81. https://doi.org/10.1016/j.diabres.2018.02.023.Wang B., Aw T.Y., Stokes K.Y. N-acetylcysteine attenuates systemic platelet activation and cerebral vessel thrombosis in diabetes. Redox Biol. 2018;14:218-28. https://doi.org/10.1016/j.redox.2017.09.005.Wang B., Aw T.Y., Stokes K.Y. N-acetylcysteine attenuates systemic platelet activation and cerebral vessel thrombosis in diabetes. Redox Biol. 2018;14:218-28. https://doi.org/10.1016/j.redox.2017.09.005.Chung W.S., Lin C.L., Kao C.H. Diabetes increases the risk of deep-vein thrombosis and pulmonary embolism. A population-based cohort study. Thromb Haemost. 2015;114(4):812-8. https://doi.org/10.1160/TH14-10-0868.Chung W.S., Lin C.L., Kao C.H. Diabetes increases the risk of deep-vein thrombosis and pulmonary embolism. A population-based cohort study. Thromb Haemost. 2015;114(4):812-8. https://doi.org/10.1160/TH14-10-0868.Wang P.C., Chen T.H., Chung C.M. et al. The effect of deep vein thrombosis on major adverse limb events in diabetic patients: a nationwide retrospective cohort study. Sci Rep. 2021;11(1):8082. https://doi.org/10.1038/s41598-021-87461-y.Wang P.C., Chen T.H., Chung C.M. et al. The effect of deep vein thrombosis on major adverse limb events in diabetic patients: a nationwide retrospective cohort study. Sci Rep. 2021;11(1):8082. https://doi.org/10.1038/s41598-021-87461-y.ACOG Practice Bulletin No. 202: Gestational hypertension and preeclampsia. Obstet Gynecol. 2019;133:e1-25. https://doi.org/10.1097/AOG.0000000000003018.ACOG Practice Bulletin No. 202: Gestational hypertension and preeclampsia. Obstet Gynecol. 2019;133:e1-25. https://doi.org/10.1097/AOG.0000000000003018.Shastri M.D., Stewart N., Eapen M. et al. Opposing effects of low molecular weight heparins on the Release of inflammatory cytokines from peripheral blood mononuclear cells of asthmatics. PLoS One. 2015;10(3):e0118798. https://doi.org/10.1371/journal.pone.0118798.Shastri M.D., Stewart N., Eapen M. et al. Opposing effects of low molecular weight heparins on the Release of inflammatory cytokines from peripheral blood mononuclear cells of asthmatics. PLoS One. 2015;10(3):e0118798. https://doi.org/10.1371/journal.pone.0118798.Zhang N., Zhan Y., Shi P. et al. LMWH inhibits TNF-a and IL-6 in placental villous explants and its effects are attenuated by TLR-4/NF-kB p65 blocking in JEG-3 cells. Int J Clin Exp Med. 2018;11:674-83.Zhang N., Zhan Y., Shi P. et al. LMWH inhibits TNF-a and IL-6 in placental villous explants and its effects are attenuated by TLR-4/NF-kB p65 blocking in JEG-3 cells. Int J Clin Exp Med. 2018;11:674-83.Wat J.M., Hawrylyshyn K., Baczyk D. et al. Effects of glycol-split low molecular weight heparin on placental, endothelial, and anti-inflammatory pathways relevant to preeclampsia. Biol Reprod. 2018;99(5):1082-90. https://doi.org/10.1093/biolre/ioy127.Wat J.M., Hawrylyshyn K., Baczyk D. et al. Effects of glycol-split low molecular weight heparin on placental, endothelial, and anti-inflammatory pathways relevant to preeclampsia. Biol Reprod. 2018;99(5):1082-90. https://doi.org/10.1093/biolre/ioy127.McLaughlin K. et al. Low molecular weight heparin improves endothelial function in pregnant women at high risk of preeclampsia. Hypertension. 2017;69(1):180-8. https://doi.org/10.1161/HYPERTENSIONAHA.116.08298.McLaughlin K. et al. Low molecular weight heparin improves endothelial function in pregnant women at high risk of preeclampsia. Hypertension. 2017;69(1):180-8. https://doi.org/10.1161/HYPERTENSIONAHA.116.08298.Yan Y., Ji Y., Su N. et al. Non-anticoagulant effects of low molecular weight heparins in inflammatory disorders: A review. Carbohydr Polym. 2017;160:71-81. https://doi.org/10.1016/j.carbpol.2016.12.037.Yan Y., Ji Y., Su N. et al. Non-anticoagulant effects of low molecular weight heparins in inflammatory disorders: A review. Carbohydr Polym. 2017;160:71-81. https://doi.org/10.1016/j.carbpol.2016.12.037.Yang C., Wu T., Huang C. Low molecular weight heparin reduces triglyceride, VLDL and cholesterol/HDL levels in hyperlipidemic diabetic patients on hemodialysis. Am J Nephrol. 1998;18(5):384-90. https://doi.org/10.1159/000013381.Yang C., Wu T., Huang C. Low molecular weight heparin reduces triglyceride, VLDL and cholesterol/HDL levels in hyperlipidemic diabetic patients on hemodialysis. Am J Nephrol. 1998;18(5):384-90. https://doi.org/10.1159/000013381.Rodger M.A., Langlois N.J., de Vries J.I. et al. Low-molecular-weight heparin for prevention of placenta-mediated pregnancy complications: protocol for a systematic review and individual patient data meta-analysis (AFFIRM). Syst Rev. 2014;3:69. https://doi.org/10.1186/2046-4053-3-69.Rodger M.A., Langlois N.J., de Vries J.I. et al. Low-molecular-weight heparin for prevention of placenta-mediated pregnancy complications: protocol for a systematic review and individual patient data meta-analysis (AFFIRM). Syst Rev. 2014;3:69. https://doi.org/10.1186/2046-4053-3-69.Bujold E., Roberge S., Lacasse Y. et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol. 2010;116(2 Pt 1):402-14. https://doi.org/10.1097/AOG.0b013e3181e9322a.Bujold E., Roberge S., Lacasse Y. et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol. 2010;116(2 Pt 1):402-14. https://doi.org/10.1097/AOG.0b013e3181e9322a.Bouvier S., Fortier M., Vincent L. et al. NETosis markers in pregnancy: effects differ according to histone subtypes. Thromb Haemost. 2021;121(7):877-90. https://doi.org/10.1055/s-0040-1722225.Bouvier S., Fortier M., Vincent L. et al. NETosis markers in pregnancy: effects differ according to histone subtypes. Thromb Haemost. 2021;121(7):877-90. https://doi.org/10.1055/s-0040-1722225.Lindmark E., Siegbahn A. Tissue factor regulation and cytokine expression in monocyte-endothelial cell co-cultures: effects of a statin, an ACE-inhibitor and a low-molecular-weight heparin. Thromb Res. 2002;108(1):77-84. https://doi.org/10.1016/s0049-3848(02)00401-2.Lindmark E., Siegbahn A. Tissue factor regulation and cytokine expression in monocyte-endothelial cell co-cultures: effects of a statin, an ACE-inhibitor and a low-molecular-weight heparin. Thromb Res. 2002;108(1):77-84. https://doi.org/10.1016/s0049-3848(02)00401-2.Momot A.P., Nikolaeva M.G., Elykomov V.A., Momot K.A. The role of APC-resistance for predicting venous thrombosis and pregnancy complications in carriers of factor V Leiden (1691) G/A mutation. In: Pregnancy and Birth Outcomes. Groatia, 2018. 33-56. https://doi.org/10.5772/intechopen.72210.Momot A.P., Nikolaeva M.G., Elykomov V.A., Momot K.A. The role of APC-resistance for predicting venous thrombosis and pregnancy complications in carriers of factor V Leiden (1691) G/A mutation. In: Pregnancy and Birth Outcomes. Groatia, 2018. 33-56. https://doi.org/10.5772/intechopen.72210.Momot A.P., Nikolaeva M.G., Yasafova N.N. et al. Clinical and laboratory manifestations of the prothrombin gene mutation in women of reproductive age. J Blood Med. 2019;10:255-63. https://doi.org/10.2147/JBM.S212759.Momot A.P., Nikolaeva M.G., Yasafova N.N. et al. Clinical and laboratory manifestations of the prothrombin gene mutation in women of reproductive age. J Blood Med. 2019;10:255-63. https://doi.org/10.2147/JBM.S212759.Nikolaeva M.G., Momot A.P., Zainulina M.S. et al. Pregnancy complications in G20210A mutation carriers associated with high prothrombin activity. Thrombosis J. 2020;19:41. https://doi.org/10.1186/s12959-021-00289-4.Nikolaeva M.G., Momot A.P., Zainulina M.S. et al. Pregnancy complications in G20210A mutation carriers associated with high prothrombin activity. Thrombosis J. 2020;19:41. https://doi.org/10.1186/s12959-021-00289-4.Momot A.P., Nikolaeva M.G., Zainulina M.S. Effects of low-molecular heparin on pregnant women with factor V mutation (GA genotype). J Hematol Blood Transfus Disord. 2018;5:20. https://doi.org/10.24966/HBTD-2999/100020(6).Momot A.P., Nikolaeva M.G., Zainulina M.S. Effects of low-molecular heparin on pregnant women with factor V mutation (GA genotype). J Hematol Blood Transfus Disord. 2018;5:20. https://doi.org/10.24966/HBTD-2999/100020(6).Nikolaeva M.G., Vakhlova Zh.I. Gene thrombophilia carriers in Altai Krai. Software registration certificate №2020663009. 2020.Nikolaeva M.G., Vakhlova Zh.I. Gene thrombophilia carriers in Altai Krai. Software registration certificate №2020663009. 2020.

The authors declare that there are no conflicts of interest present.