clinmedКлиническая медицинаClinical Medicine (Russian Journal)0023-21492412-1339ООО «Медицинское информационное агентство»10.30629/0023-2149-2021-99-1-15-20clinmed-174Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESТромбофилия в акушерской практикеThrombophilia in obstetric practicehttps://orcid.org/0000-0002-7426-9040МельниковА. П.MelnikovA. P.

101000, Москва,

129327, Москва

101000, Moscow,

129327, Moscow

https://orcid.org/0000-0003-2679-3734КащукМ. Г.KashchukM. G.

Кащук Марина Геннадьевна — аспирант

101000, Москва

Kashchuk Marina G. — graduate student

101000, Moscow

marina.kaschchuk@yandex.ruАхвледианиК. Н.AhvledianiK. N.

101000, Москва

101000, Moscow

https://orcid.org/0000-0001-5331-2655БокаревИ. Н.BokarevI. N.

129327, Москва

129327, Moscow

ГБУЗ МО «Московский областной научно-исследовательский институт акушерства и гинекологии»; Всероссийская ассоциация по изучению тромбозов, геморрагий и патологии сосудов им. А.А. Шмидта–Б.А. КудряшоваРоссияThe State Budgetary Healthcare Institution of the Moscow Region Moscow Regional Research Institute of Obstetrics and Gynecology; Russian Association on Thrombosis, Haemostasis and Vascular Pathology named after A. Schmidt–B. KudryashovRussian FederationГБУЗ МО «Московский областной научно-исследовательский институт акушерства и гинекологии»РоссияThe State Budgetary Healthcare Institution of the Moscow Region Moscow Regional Research Institute of Obstetrics and GynecologyRussian FederationВсероссийская ассоциация по изучению тромбозов, геморрагий и патологии сосудов им. А.А. Шмидта–Б.А. КудряшоваРоссияRussian Association on Thrombosis, Haemostasis and Vascular Pathology named after A. Schmidt–B. KudryashovRussian Federation2021030620219911520Copyright © Мельников А.П., Кащук М.Г., Ахвледиани К.Н., Бокарев И.Н., 20212021Мельников А.П., Кащук М.Г., Ахвледиани К.Н., Бокарев И.Н.Melnikov A.P., Kashchuk M.G., Ahvlediani K.N., Bokarev I.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.clinmedjournal.com/jour/article/view/174

Частота тромбоэмболических осложнений, связанных с тромбофилией, очень высока, поэтому обнаружение мутаций тромбофилии в группе пациенток высокого риска важно для профилактики заболеваемости, смертности и акушерских потерь. Проблемой тромбофилии занимаются врачи разных специальностей: лабораторные сотрудники, генетики, сосудистые хирурги, гематологи, неврологи, кардиологи и акушеры-гинекологи. При этом пациенты, имеющие спонтанные тромбозы без видимой причины, наблюдаются годами без должного обследования на тромбофилию. Учитывая, что беременность является состоянием, связанным с высокой вероятностью ретромбозов, целесообразно определять причину и тактику ведения и лечения беременных в максимально ранние сроки беременности.

The rate of thromboembolic complications associated with thrombophilia is very high; therefore the detection of thrombophilia mutations in the high-risk group of patients is important for the prevention of morbidity, mortality and obstetric losses. The problem of thrombophilia is dealt with by doctors of various specialties: laboratory stuff, geneticists, vascular surgeons, hematologists, neurologists, cardiologists and obstetricians-gynecologists. At the same time, patients with spontaneous thrombosis are followed-up for years without proper examination for thrombophilia. Considering that pregnancy is a condition associated with a high probability of re-thrombosis, it is advisable to determine the cause and tactics of management and treatment of pregnant women as early as possible during the period of pregnancy.

тромбофилиятромбозыакушерские потериthrombophiliathrombosesobstetric lossesReferencesPetrukhin V.A., Melnikov A.P., Budykina T.S., Ratnikov A.O. Possibilities of laboratory control of preventive doses of heparin in obstetric practice. Proceedings of the XXI National Congress with International Participation «Thrombosis, bleeding, and permanent intravascular coagulation» on October 11–13, 2017 in St. Petersburg. 2017;43–44. (in Russian.)Petrukhin V.A., Melnikov A.P., Budykina T.S., Ratnikov A.O. Possibilities of laboratory control of preventive doses of heparin in obstetric practice. Proceedings of the XXI National Congress with International Participation «Thrombosis, bleeding, and permanent intravascular coagulation» on October 11–13, 2017 in St. Petersburg. 2017;43–44. (in Russian.)Bates S.M., Greer I.A., Middeldorp S. et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic therapy and prevention of thrombosis 9th ed. American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012; 141:691–736.Bates S.M., Greer I.A., Middeldorp S. et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic therapy and prevention of thrombosis 9th ed. American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012; 141:691–736.Grandone E., Tomaiuolo M., Colaizzo D. et al. Role of thrombophilia in adverse obstetric outcomes and their prevention using anti thrombotic therapy. Semin. Thromb. Hemost. 2009;35:630–43.Grandone E., Tomaiuolo M., Colaizzo D. et al. Role of thrombophilia in adverse obstetric outcomes and their prevention using anti thrombotic therapy. Semin. Thromb. Hemost. 2009;35:630–43.Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thromb. Diath. Haemorrh. 1965;13:516–30. Cited by I.N. Bokarev «Hematology for a practical doctor». MIA, Moscow. 2018:227. (in Russian.)Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thromb. Diath. Haemorrh. 1965;13:516–30. Cited by I.N. Bokarev «Hematology for a practical doctor». MIA, Moscow. 2018:227. (in Russian.)Franco R.F., Reitsma P.H. Genetic risk factors of venous thrombosis. Hum. Genet. 2001;109:369–84.Franco R.F., Reitsma P.H. Genetic risk factors of venous thrombosis. Hum. Genet. 2001;109:369–84.Schwarz H.P., Fischer M., Hopmeier P., Batard M.A., Griffin J.H. Plasma protein S deficiency in familial thrombotic disease. Blood. 1984;64:1297–1300.Schwarz H.P., Fischer M., Hopmeier P., Batard M.A., Griffin J.H. Plasma protein S deficiency in familial thrombotic disease. Blood. 1984;64:1297–1300.Rosendaal F.R. Risk factors for venous thrombotic disease. Thromb. Haemost. 1999;82:610–9.Rosendaal F.R. Risk factors for venous thrombotic disease. Thromb. Haemost. 1999;82:610–9.Parand A., Zolghadri J., Nezam M., Afrasiabi A., Haghpanah S., Karimi M. Inherited thrombophilia and recurrent pregnancy loss. Iran Red. Crescent Med. J. 2013;15(12):13708.Parand A., Zolghadri J., Nezam M., Afrasiabi A., Haghpanah S., Karimi M. Inherited thrombophilia and recurrent pregnancy loss. Iran Red. Crescent Med. J. 2013;15(12):13708.Folkeringa N., Liindert G., Brouwer P. et al. Redaction of high fetal loss rate by anticoagulant treatment during pregnancy in antitrombin, proyein C or protein S deficint women. Br. J. Haematol. 2017;136:4:656–61.Folkeringa N., Liindert G., Brouwer P. et al. Redaction of high fetal loss rate by anticoagulant treatment during pregnancy in antitrombin, proyein C or protein S deficint women. Br. J. Haematol. 2017;136:4:656–61.Galli М. Treatment of the antiphospholipid syndrome. Autoimmun. Highlights. 2013;22;5(1):1–7.Galli М. Treatment of the antiphospholipid syndrome. Autoimmun. Highlights. 2013;22;5(1):1–7.Castro-Marrero J., Balada E., Vilardell-Tarrés M., Ordi-Ros J. Genetic Risk Factors of Thrombosis in the Antiphospholipid Syndrome. Br. J. Haematol. 2009;147(3):289–96.Castro-Marrero J., Balada E., Vilardell-Tarrés M., Ordi-Ros J. Genetic Risk Factors of Thrombosis in the Antiphospholipid Syndrome. Br. J. Haematol. 2009;147(3):289–96.Miyakis S., Lockshin M., Atusmi T. et al. International consensus statement on an update of the classification criteria for defnite antiphospholipid syndrome (APS). J. Thromb. Haemost. 2006;4: 295–30.Miyakis S., Lockshin M., Atusmi T. et al. International consensus statement on an update of the classification criteria for defnite antiphospholipid syndrome (APS). J. Thromb. Haemost. 2006;4: 295–30.James A.H., Tapson V.F., Goldhaber S.Z. Thrombosis during pregnancy and the postpartum period. Am. J. Obstet. Gynecol. 2005;193:216–219.James A.H., Tapson V.F., Goldhaber S.Z. Thrombosis during pregnancy and the postpartum period. Am. J. Obstet. Gynecol. 2005;193:216–219.Bertina R.M., Koeleman R.P.C., Koster T. et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature. 1994;369:64–67.Bertina R.M., Koeleman R.P.C., Koster T. et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature. 1994;369:64–67.Ben Salem-Berrabah O., Fekih-Mrissa N., N’siri B., Ben Hamida A., Benammar-Elgaaied A., Gritli N., Mrissa R. Thrombophilic polymorphisms — factor V Leiden G1691A, prothrombin G20210A and MTHFR C677T — in Tunisian patients with cerebral venous thrombosis. J. Clin. Neurosci. 2012;19(9):1326–7.Ben Salem-Berrabah O., Fekih-Mrissa N., N’siri B., Ben Hamida A., Benammar-Elgaaied A., Gritli N., Mrissa R. Thrombophilic polymorphisms — factor V Leiden G1691A, prothrombin G20210A and MTHFR C677T — in Tunisian patients with cerebral venous thrombosis. J. Clin. Neurosci. 2012;19(9):1326–7.Poort S.R., Rosendaal F.R., Reitsma P.H., Bertina R.M. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. 1996;88:3698–3703.Poort S.R., Rosendaal F.R., Reitsma P.H., Bertina R.M. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. 1996;88:3698–3703.Nikitina I.V., Boychuk A.N. The possibilities of predicting miscarriage in multiple pregnancies by evaluating genetic predictors. Journal of the Grodno State Medical University. 2017;1:76. (in Russian.)Nikitina I.V., Boychuk A.N. The possibilities of predicting miscarriage in multiple pregnancies by evaluating genetic predictors. Journal of the Grodno State Medical University. 2017;1:76. (in Russian.)Monari F., Alberico S., Avagliano L., Cetin I., Cozzolino S., Gargano G., Marozio L., Mecacci F., Neri I., Tranquilli A.L., Venturini P., Facchinetti F. Relation between maternal thrombophilia and stillbirth according to causes/associated conditions of death. Early Hum. Dev. 2012;88(4):251–254.Monari F., Alberico S., Avagliano L., Cetin I., Cozzolino S., Gargano G., Marozio L., Mecacci F., Neri I., Tranquilli A.L., Venturini P., Facchinetti F. Relation between maternal thrombophilia and stillbirth according to causes/associated conditions of death. Early Hum. Dev. 2012;88(4):251–254.Rosendaal F.R., Doggern C.J., Zivelin A. et al. Geographic distribution of the 20210 G to A prothrombin variant. Thromb. Haemost. 1998;79:706–708.Rosendaal F.R., Doggern C.J., Zivelin A. et al. Geographic distribution of the 20210 G to A prothrombin variant. Thromb. Haemost. 1998;79:706–708.Isaoglu U., Ulug P., Delibas I.B., Yilmaz M., Kumtepe Y., Dogan H., Tasdemir S. The association between inherited thrombophilia and recurrent pregnancy loss in Turkish women. Clin. Exp. Obstet. Gynecol. 2014;41(2):177–181.Isaoglu U., Ulug P., Delibas I.B., Yilmaz M., Kumtepe Y., Dogan H., Tasdemir S. The association between inherited thrombophilia and recurrent pregnancy loss in Turkish women. Clin. Exp. Obstet. Gynecol. 2014;41(2):177–181.Hamani N.M. Features of the management of pregnancy and childbirth in a woman with a homozygous prothrombin mutation (Thr165Met) and a history of recurrent pulmonary embolism while taking hormonal contraception. Obstetrics, gynecology and reproduction. 2018;12(1):99–104. (in Russian.)Hamani N.M. Features of the management of pregnancy and childbirth in a woman with a homozygous prothrombin mutation (Thr165Met) and a history of recurrent pulmonary embolism while taking hormonal contraception. Obstetrics, gynecology and reproduction. 2018;12(1):99–104. (in Russian.)Djordjevic V., Stankovic M., Brankovic-Sreckovic V., Rakicevic L., Damnjanovic T., Antonijevic N., Radojkovic D. Prothrombotic genetic risk factors in stroke: a possible different role in pediatric and adult patients. Clin. Appl. Thromb. Hemost. 2012;18(6):658–661.Djordjevic V., Stankovic M., Brankovic-Sreckovic V., Rakicevic L., Damnjanovic T., Antonijevic N., Radojkovic D. Prothrombotic genetic risk factors in stroke: a possible different role in pediatric and adult patients. Clin. Appl. Thromb. Hemost. 2012;18(6):658–661.Nikolaeva M.G., Grigorieva E.E., Serdyuk G.V., Momot A.P. The role of genetic determinants of thrombophilia in the realization of a woman’s reproductive function. Materials of the 10th Anniversary Russian Scientific Forum «Mother and Child». 29.09–02.10.2009 Moscow, 2009:144–145. (in Russian.)Nikolaeva M.G., Grigorieva E.E., Serdyuk G.V., Momot A.P. The role of genetic determinants of thrombophilia in the realization of a woman’s reproductive function. Materials of the 10th Anniversary Russian Scientific Forum «Mother and Child». 29.09–02.10.2009 Moscow, 2009:144–145. (in Russian.)Zainullin I.A., Kulavsky V.A., Zainullina A.G., Khustnutdinova E.K. The role of genes of the fi brinolytic system in the occurrence of gestosis. Materials of the 10th Anniversary Russian Scientific Forum «Mother and Child». 29.09–02.10.2009 Moscow, 2009:69. (in Russian.)Zainullin I.A., Kulavsky V.A., Zainullina A.G., Khustnutdinova E.K. The role of genes of the fibrinolytic system in the occurrence of gestosis. Materials of the 10th Anniversary Russian Scientific Forum «Mother and Child». 29.09–02.10.2009 Moscow, 2009:69. (in Russian.)Ivanov P., Komsa-Penkova R., Ivanov I., Konova E., Kovacheva K., Simeonova M., Tanchev S. Plasminogen activator inhibitor type 1 activity in women with unexplained very early recurrent pregnancy loss. Akush. Ginekol. (Sofiia). 2010;49(5):3–8.Ivanov P., Komsa-Penkova R., Ivanov I., Konova E., Kovacheva K., Simeonova M., Tanchev S. Plasminogen activator inhibitor type 1 activity in women with unexplained very early recurrent pregnancy loss. Akush. Ginekol. (Sofiia). 2010;49(5):3–8.Den Heijer M., Lewington S., Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J. Thromb. Haemost. 2005;3:292–299.Den Heijer M., Lewington S., Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J. Thromb. Haemost. 2005;3:292–299.Key N.S., McGlennen RC. Hyperhomocyst(e)inemia and Throm bophilia. Arch Pathol. Lab. Med. 2002;126(11):1367–1375.Key N.S., McGlennen RC. Hyperhomocyst(e)inemia and Throm bophilia. Arch Pathol. Lab. Med. 2002;126(11):1367–1375.Cueto R., Zhang L., Shan H.M., Huang X., Li X., Li Y.F., Lopez J., Yang W.Y., Lavallee M., Yu C., Ji Y., Yang X., Wang H. Identification of homocysteine-suppressive mitochondrial ETC complex genes and tissue expression profile — Novel hypothesis establishment. Redox Biol. 2018;17:70–88.Cueto R., Zhang L., Shan H.M., Huang X., Li X., Li Y.F., Lopez J., Yang W.Y., Lavallee M., Yu C., Ji Y., Yang X., Wang H. Identification of homocysteine-suppressive mitochondrial ETC complex genes and tissue expression profile — Novel hypothesis establishment. Redox Biol. 2018;17:70–88.Hakim R.M. Clinical implications of hemodialysis membrane biocompatibility. Kidney Int. 1993;44(3):484–94.Hakim R.M. Clinical implications of hemodialysis membrane biocompatibility. Kidney Int. 1993;44(3):484–94.Bosch-Marcé M., Pola R., Wecker A.B., Silver M., Weber A., Luedemann C., Curry C., Murayama T., Kearney M., Yoon Y.S., Malinow M.R., Asahara T., Isner J.M., Losordo D.W. Hyper homocyst(e)inemia impairs angiogenesis in a murine model of limb ischemia. Vasc. Med. 2005Feb;10(1):15–22.Bosch-Marcé M., Pola R., Wecker A.B., Silver M., Weber A., Luedemann C., Curry C., Murayama T., Kearney M., Yoon Y.S., Malinow M.R., Asahara T., Isner J.M., Losordo D.W. Hyper homocyst(e)inemia impairs angiogenesis in a murine model of limb ischemia. Vasc. Med. 2005Feb;10(1):15–22.Gumus E. The powerful association of angiotensin-converting enzyme insertion/deletion polymorphismand idiopathic recurrent pregnancy loss. Ginekol. Pol. 2018;89(10):573–576.Gumus E. The powerful association of angiotensin-converting enzyme insertion/deletion polymorphismand idiopathic recurrent pregnancy loss. Ginekol. Pol. 2018;89(10):573–576.Wang Z., Wang P., Wang X., He X., Wang Z., Xu D., Hu J., Wang B. Significant association between angiotensin-converting enzyme gene insertion/deletion polymorphism and risk of recurrent miscarriage: a systematic review and meta-analysis. Metabolism. 2013;62(9): 1227–1238.Wang Z., Wang P., Wang X., He X., Wang Z., Xu D., Hu J., Wang B. Significant association between angiotensin-converting enzyme gene insertion/deletion polymorphism and risk of recurrent miscarriage: a systematic review and meta-analysis. Metabolism. 2013;62(9): 1227–1238.Nakamura E., Okamoto T., Nagaya K., Hayashi T. Maternal deletion allele of Angiotensin-converting enzyme gene is associated with fetal growth restriction. Pediatr. Dev. Pathol. 2012;15(2):114–7.Nakamura E., Okamoto T., Nagaya K., Hayashi T. Maternal deletion allele of Angiotensin-converting enzyme gene is associated with fetal growth restriction. Pediatr. Dev. Pathol. 2012;15(2):114–7.Chatzidimitriou M., Chatzidimitriou D., Mavridou M., Anetakis C., Chatzopoulou F., Lialiaris T., Mitka S. Thrombophilic gene polymorphisms and recurrent pregnancy loss in Greek women. Int. J. Lab. Hematol. 2017;39(6):590–595.Chatzidimitriou M., Chatzidimitriou D., Mavridou M., Anetakis C., Chatzopoulou F., Lialiaris T., Mitka S. Thrombophilic gene polymorphisms and recurrent pregnancy loss in Greek women. Int. J. Lab. Hematol. 2017;39(6):590–595.Simioni P. Thrombophilia and gestational VTE. Thrombosis Research. 2009;123(2):41–44.Simioni P. Thrombophilia and gestational VTE. Thrombosis Research. 2009;123(2):41–44.Aggarwal S., Dimri N., Tandon I., Agarwal S. Рreeclampsia in North Indian women: the contribution of genetic polymorphisms. J. Obstet. Gynaecol. Research. 2011; 37(10):1335–1341.Aggarwal S., Dimri N., Tandon I., Agarwal S. Рreeclampsia in North Indian women: the contribution of genetic polymorphisms. J. Obstet. Gynaecol. Research. 2011; 37(10):1335–1341.

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