akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347/ob.gyn.rep.2024.586akusherstvo-2275Research ArticleОRIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИGenetic thrombophilia and antiphospholipid antibodies in women with early and late preeclampsia: a retrospective cohort studyГенетическая тромбофилия и антифосфолипидные антитела у женщин с ранней и поздней преэклампсией: ретроспективное когортное исследованиеhttps://orcid.org/0000-0002-4534-2157АнтоноваА. С.AntonovaA. S.

Антонова  Александра  Сергеевна 

Scopus Author ID: 57215934525

119991 Москва, ул. Трубецкая, д. 8, стр. 2

Alexandra S. Antonova, MD.

Scopus Author ID: 57215934525

8 bldg. 2, Trubetskaya Str., Moscow 119991

Antonova.snk@inbox.ruhttps://orcid.org/0000-0002-0725-9686ХизроеваД. Х.KhizroevaJ. Kh.

Хизроева Джамиля Хизриевна, д.м.н., проф.

Scopus Author ID: 57194547147

WoS ResearcherID: F-8384-2017

119991 Москва, ул. Трубецкая, д. 8, стр. 2

Jamilya Kh. Khizroeva, MD, Dr Sci Med, Prof.

Scopus Author ID: 57194547147

WoS ResearcherID: F-8384-2017

8 bldg. 2, Trubetskaya Str., Moscow 119991

https://orcid.org/0000-0001-8404-1042БицадзеВ. О.BitsadzeV. O.

Бицадзе Виктория Омаровна, д.м.н., проф., профессор РАН

Scopus Author ID: 6506003478

WoS ResearcherID: F-8409-2017

119991 Москва, ул. Трубецкая, д. 8, стр. 2

Victoria O. Bitsadze, MD, Dr Sci Med, Prof., Professor RAS.

Scopus Author ID: 6506003478

WoS ResearcherID: F-8409-2017

8 bldg. 2, Trubetskaya Str., Moscow 119991

ТретьяковаМ. В.TretyakovaM. V.

Третьякова Мария Владимировна, к.м.н.

119991 Москва, ул. Трубецкая, д. 8, стр. 2

Maria V. Tretyakova, MD, PhD.

8 bldg. 2, Trubetskaya Str., Moscow 119991

https://orcid.org/0000-0002-2541-3843МакацарияН. А.MakatsariyaN. A.

Макацария Наталия Александровна, к.м.н.

WoS ResearcherID: F-8406-2017

119991 Москва, ул. Трубецкая, д. 8, стр. 2

Nataliya A. Makatsariya, MD, PhD.

WoS ResearcherID: F-8406-2017

8 bldg. 2, Trubetskaya Str., Moscow 119991

https://orcid.org/0009-0001-0548-6420ЭфендиеваЭ. Р.EfendievaE. R.

Эфендиева  Эльвира  Раджабулаховна 

119991 Москва, ул. Трубецкая, д. 8, стр. 2

Elvira R. Efendieva, MD.

8 bldg. 2, Trubetskaya Str., Moscow 119991

https://orcid.org/0009-0006-6018-4667ШатилинаА. Ю.ShatilinaA. Yu.

Шатилина Анастасия Юрьевна

119991 Москва, ул. Трубецкая, д. 8, стр. 2

Anastasia Yu. Shatilina

8 bldg. 2, Trubetskaya Str., Moscow 119991

https://orcid.org/0009-0004-6971-8552ЛядноваЕ. М.LyadnovaE. M.

Ляднова Елизавета Михайловна

119991 Москва, ул. Трубецкая, д. 8, стр. 2

Elizaveta M. Lyadnova

8 bldg. 2, Trubetskaya Str., Moscow 119991

ФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский университет)РоссияSechenov UniversityRussian Federation2025251220241911425Copyright © Antonova A.S., Khizroeva J.K., Bitsadze V.O., Tretyakova M.V., Makatsariya N.A., Efendieva E.R., Shatilina A.Y., Lyadnova E.M., 20252025Антонова А.С., Хизроева Д.Х., Бицадзе В.О., Третьякова М.В., Макацария Н.А., Эфендиева Э.Р., Шатилина А.Ю., Ляднова Е.М.Antonova A.S., Khizroeva J.K., Bitsadze V.O., Tretyakova M.V., Makatsariya N.A., Efendieva E.R., Shatilina A.Y., Lyadnova E.M.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/2275Aim

Aim: to study a pattern of genetic and acquired thrombophilia in pregnant women with severe early-onset (eoPЕ) and severe lateonset (loPЕ) preeclampsia (PE).

Materials and Methods

Materials and Methods. A retrospective cohort study was conducted from January 2022 to May 2024. A total of 109 pregnant women were examined: group 1 – 45 women with eoPЕ (< 34 weeks of pregnancy), group 2 – 24 women with loPЕ (≥ 34 weeks of pregnancy), group 3 (control) – 40 women with physiologically uncomplicated pregnancy. All pregnant women were examined for lupus anticoagulant (LA) and antiphospholipid antibodies (aPL). The screening test for aPL included the quantitation of IgG/IgM antibodies against cardiolipin, phosphatidylserine, phosphatidylinositol, phosphatidic acid, and β2-glycoprotein 1 in serum or plasma using an enzyme immunoassay. Genetic thrombophilia, homocysteine, and ADAMTS-13 metalloproteinase (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) levels were also determined.

Results

Results. Pregnant women with severe PE more often had genetic forms of thrombophilia (mutations in factor (F) V Leiden gene, prothrombin G20210A, and Thr165Met) and a deficiency of natural anticoagulants (antithrombin and protein S) compared to pregnant women in control group. Women in eoPE vs. loPE group were more often found to carry genetic polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) and fibrinogen genes. Also, in the group of pregnant women with eoPE, the circulation of aPL, ADAMTS-13 inhibitor, and elevated homocysteine levels were more common. Pregnant women with loPE were older and more often suffered from hypertension, diabetes mellitus, and excess body weight. No significant differences between eoPЕ and loPЕ groups were found while comparing prevalence of autoimmune diseases, thrombosis in familial history, mutations in FV Leiden gene (heterozygous form), FII prothrombin gene G20210A (homozygous form), FII prothrombin gene Thr165Met (heterozygous form), antithrombin III deficiency, protein S deficiency.

Conclusion

Conclusion. Precise causes underlying PE remain unknown, andwe are still far from understanding all the molecular, immunological, genetic, and environmental mechanisms that lead to the various clinical manifestations of placental syndromes including PE. However, the study results suggest that the presence of thrombophilic disorders, especially in the fibrinolytic system, and aPL circulation contribute to eoPE pathophysiology or progression.

Цель

Цель: изучить структуру генетической и приобретенной тромбофилии у беременных с тяжелой преэклампсией (ПЭ) с ранним началом (РПЭ) и тяжелой ПЭ с поздним началом (ППЭ).

Материалы и методы

Материалы и методы. Проведено ретроспективное когортное исследование в период с января 2022 г. по май 2024 г. Обследовано 109 беременных: группа 1 – 45 женщин с РПЭ (< 34 нед беременности), группа 2 – 24 женщины с ППЭ (≥ 34 нед беременности), группа 3 (контрольная) – 40 женщин с физиологически протекающей беременностью без осложнений. Все беременные были обследованы на наличие циркуляции волчаночного антикоагулянта (ВА) и антифосфолипидных антител (АФА). Скрининговый тест на АФА включал количественное определение IgG/IgM антител к кардиолипину, фосфатидилсерину, фосфатидилинозиту, фосфатидной кислоте и β2-гликопротеину 1 в сыворотке или плазме крови иммуноферментным методом. Также проведено определение генетической тромбофилии, уровня гомоцистеина и металлопротеиназы ADAMTS-13 (англ. a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13).

Результаты

Результаты. Беременные с тяжелой ПЭ чаще имели генетические формы тромбофилии (мутации в гене фактора (F) V Leiden, протромбина G20210A и Thr165Met) и дефицит естественных антикоагулянтов (антитромбина и протеина S) по сравнению с беременными контрольной группы. Беременные в группе РПЭ чаще являлись носителями генетических полиморфизмов в гене ингибитора активатора плазминогена-1 (англ. plasminogen activator inhibitor-1, PAI-1) и фибриногена по сравнению с женщинами в группе ППЭ. Также в группе беременных с РПЭ чаще встречалась циркуляция АФА, ингибитора ADAMTS-13 и повышенный уровень гомоцистеина. Беременные с ППЭ были старше по возрасту и чаще имели артериальную гипертензию, сахарный диабет и избыточную массу тела. Между группами с РПЭ и ППЭ не удалось установить статистически значимых различий при сопоставлении аутоиммунных заболеваний, тромбозов в семейном анамнезе, мутаций в гене FV Leiden (гетерозиготная форма), в гене FII протромбина G20210A (гомозиготная форма), в гене FII протромбина Thr165Met (гетерозиготная форма), дефицита антитромбина III, дефицита протеина S.

Заключение

Заключение. Точные причины развития ПЭ неизвестны, и мы все еще далеки от понимания всех молекулярных, иммунологических, генетических и экологических механизмов, приводящих к различным клиническим проявлениям плацентарных синдромов, одним из которых является ПЭ. Однако результаты исследования позволяют предположить, что наличие тромбофилических нарушений, особенно в системе фибринолиза, а также циркуляция АФА способствуют патофизиологии или прогрессированию РПЭ.

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