rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.47360/1995-4484-2024-408-417rsp-3608Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHТромботический антифосфолипидный синдром: рецидивы тромбозовThrombotic antiphospholipid syndrome: Recurrent thromboseshttps://orcid.org/0000-0003-3552-2522РешетнякТ. М.ReshetnyakTatiana M.

Решетняк Татьяна Магомедалиевна

115522, Москва, Каширское шоссе, 34а

125993, Москва, ул. Баррикадная, 2/1, стр. 1 

115522, Moscow, Kashirskoye Highway, 34A

125993, Moscow, Barrikadnaya str., 2/1, building 1 

t_reshetnyak@yahoo.comhttps://orcid.org/0000-0001-5217-4932ЧельдиеваФ. А.CheldievaFariza A.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0002-4285-0869ГлуховаС. И.GlukhovaSvetlana I.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0001-6685-7670НурбаеваК. С.NurbaevaKamila S.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0001-5781-2964СередавкинаН. В.SeredavkinaNataliya V.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0002-3246-1157ЧеркасоваМ. В.CherkasovaMariya V.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0002-6068-3080ЛилаА. М.LilaAlexander M.

115522, Москва, Каширское шоссе, 34а

125993, Москва, ул. Баррикадная, 2/1, стр. 1 

115522, Moscow, Kashirskoye Highway, 34A

125993, Moscow, Barrikadnaya str., 2/1, building 1 

https://orcid.org/0000-0002-1598-8360НасоновЕ. Л.NasonovEvgeny L.

115522, Москва, Каширское шоссе, 34а

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

115522, Moscow, Kashirskoye Highway, 34A

119991, Moscow, Trubetskaya str., 8, building 2

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииРоссияV.A. Nasonova Research Institute of Rheumatology; Russian Medical Academy of Continuous Professional Education of the Ministry of Healthcare of the Russian FederationRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияV.A. Nasonova Research Institute of Rheumatology; I.M. Sechenov First Moscow State Medical University of the Ministry of Health Care of the Russian Federation (Sechenov University)Russian Federation202402092024624408–417Copyright © Решетняк Т.М., Чельдиева Ф.А., Глухова С.И., Нурбаева К.С., Середавкина Н.В., Черкасова М.В., Лила А.М., Насонов Е.Л., 20242024Решетняк Т.М., Чельдиева Ф.А., Глухова С.И., Нурбаева К.С., Середавкина Н.В., Черкасова М.В., Лила А.М., Насонов Е.Л.Reshetnyak T.M., Cheldieva F.A., Glukhova S.I., Nurbaeva K.S., Seredavkina N.V., Cherkasova M.V., Lila A.M., Nasonov E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/3608

Тромботический антифосфолипидный синдром (АФС) – это состояние, поражающее молодых людей, у которых тромбоэмболическое событие возникает в присутствии циркулирующих антифосфолипидных антител (аФЛ).

Цель исследования – оценить частоту рецидивов тромбозов и факторы их риска при антифосфолипидном синдроме.

Материал и методы

Материал и методы. В ретроспективное исследование были включены 98 пациентов с АФС, наблюдавшихся в ФГБНУ НИИР им. В.А. Насоновой с 2014 по 2023 г. Среди них было 66 (67%) женщин и 32 (33%) мужчины. Системная красная волчанка (СКВ) диагностирована у 48 (49%) из 98 больных АФС. Определялись IgG/IgM-антитела к кардиолипину (аКЛ), β2-гликопротеину 1 (аβ2ГП1), IgG-антитела к домену 1 β2-гликопротеина 1 (аβ2ГП1-D1), IgG/IgM-антитела к комплексу фосфатидилсерин/протромбин (aФС/ПТ) и другие факторы риска тромбоза. Для определения уровня аФЛ использовался иммуноферментный (ИФА) и хемолюминесцентный (ХЛА) анализ.

Результаты

Результаты. Рецидивы тромбозов были зарегистрированы у 62 (63%) из 98 больных. У 24 (38,7%) из 62 пациентов с рецидивирующими тромбозами основной причиной рецидивов была терапия прямыми пероральными антикоагулянтами (ПОАК), длительность приема которых колебалась от 6 до 24 месяцев. Отсутствие постоянной антикоагулянтной терапии у 20 (32,5%) больных было следующим по частоте фактором риска рецидивов. У 17 (27,4%) пациентов рецидивы тромбозов регистрировались на фоне приема варфарина. Рецидивы тромбозов у 10 (41,7%) из 24 пациентов, получающих ПОАК, были артериальной локализации (повторные нарушения мозгового кровообращения). Уровень позитивности по аФЛ не имел значения, но все они имели тройную позитивность по IgG аФЛ, у 5 в дебюте заболевания до назначения антикоагулянтов выявлялся волчаночный антикоагулянт (ВА). По данным ИФА наибольшее значение в отношении рецидива тромбоза имели IgG аФС/ПТ: 45 (72,6%) из 62 пациентов с рецидивами тромбозов были позитивны по IgG аФС/ПТ против 19 (52,8%) из 36 без рецидива тромбоза. При использовании ХЛА аФЛ выявлялись чаще, чем с помощью ИФА; тем не менее, в последних классификационных критериях рекомендовано определение аФЛ методом ИФА. Тройная позитивность по IgG аКЛ, IgG аβ2ГП1, IgG аβ2ГП1-D1 по данным ХЛА также оставалась фактором риска рецидива тромбоза, и риск рецидива возрастал более чем в 3 раза.

Ожирение повышало риск рецидива тромбоза в 5 раз по сравнению с теми, у кого его не было (р=0,01).

Выводы

Выводы. Рецидивирующий тромбоз при АФС в значительной степени связан с позитивностью по IgG aКЛ, IgG аβ2ГП1, IgG аβ2ГП1-D1, IgG aФС/ПT. Риск рецидива тромбоза значительно возрастал при тройной позитивности по IgG аФЛ в любой их комбинации. Наличие IgG аФЛ любых типов, выявленных как при использовании ИФА, так и с помощью ХЛА, влияло на частоту рецидива тромбоза при АФС.

Ожирение было значимым фактором риска повторного тромбоза.

Thrombotic antiphospholipid syndrome (APS) is a condition affecting young people in whom a thromboembolic event occurs in the presence of circulating antiphospholipid antibodies (aPL).

The aim of this study was the evaluation of the incidence of recurrent thrombosis and its risk factors in antiphospholipid syndrome.

Material and methods

Material and methods. The retrospective study included 98 patients with aPL who were followed up at the institute from 2014 to 2023, of whom 66 (67%) were women and 32 (33%) were men. Of the 98 patients with aPL, 48 (49%) had a diagnosis of systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL), including antibodies to cardiolipin (IgG/IgM aCL), antibodies to ß2-glycoprotein 1 (IgG/IgM aß2GP1), antibodies to ß2-glycoprotein IgG against domain 1 (IgG aß2GP1-D1), antibodies to phosphatidylserine/prothrombin complex (IgG/ IgM aPS/PT) and other thrombotic risk factors. aPL was assessed by enzyme-linked immunosorbent assay (ELISA) and chemoluminescence assay (CHLA).

Results

Results. Thrombosis recurrence was reported in 62 (63%) of 98 patients, and 36 (35%) did not. The main cause of recurrent thrombosis was treatment with direct oral anticoagulants (DOACs). 24 (38.7%) of 62 patients with recurrent thrombosis were treated with DOACs, the duration of which ranged from 6 to 24 months. The next most common cause of recurrent thrombosis was the lack of continuous anticoagulant therapy in 20 (32.5%) of the patients. In 17 (27.4%) of the patients, the recurrence occurred while they were still taking warfarin. In 10 (41.7%) of the 24 patients, the recurrent thrombosis was arterial in origin. This was associated with recurrent cerebral circulation problems. The level of positivity did not matter, but all had triple IgG aPL positivity. 5 had lupus anticoagulant (LA) at the onset of the disease before anticoagulant use. IgG aPS/PT was most important in association with recurring thrombosis in the ELISA: 45 (72.6%) of 62 patients with recurring thrombosis were positive for IgG aPS/PT, compared with 19 (52.8%) of 36 patients without recurring thrombosis. The detection of all aPL was more frequent in CHMA than in ELISA. However, the definition of aPL in ELISA is recommended according to the latest classification criteria. Triple IgG positivity for aCL of IgG aß2GP1, IgG aß2GP1-D1 and CHMA remained a risk factor for recurrent thrombosis and increased the risk of recurrence more than threefold. Obesity was a risk factor for recurrent thrombosis, with a 5-fold increased risk of recurrent thrombosis in obese compared to non-obese patients (p=0.01).

Conclusions

Conclusions. Recurrent thrombosis in APS is largely associated with IgG aCL, IgG aß2GP1, IgG aß2GP1-D1, IgG aPS/PT. Triple IgG aPL positivity in any combination significantly increased recurrent thrombosis risk.

The presence of any type of aPL IgG in both ELISA and CHLA influenced the recurrence rate of thrombosis in APS.

Obesity was a significant risk factor for recurrent thrombosis.

антифосфолипидный синдромантифосфолипидные антителарецидивы тромбозовсистемная красная волчанкаантитела к кардиолипинуантитела к бета-2-гликопротеину 1антитела к комплексу фосфатидилсерин/протромбинantiphospholipid syndromeantiphospholipid antibodiesrecurrent thrombosessystemic lupus erythematosusantibodies to cardiolipinantibodies to ß2-glycoprotein 1antibodies to phosphatidylserine/prothrombin complexСтатья подготовлена в рамках темы ФГБНУ НИИР им. В.А. Насоновой FURS-2022-003 (№ 122040400024-7), и исследование одобрено локальным этическим комитетом.ReferencesРешетняк ТМ. Антифосфолипидный синдром: диагностика и клинические проявления (лекция). Научно-практическая ревматология. 2014;52(1):56-71. doi: 10.14412/19954484-2014-56-71.Reshetnyak TM. Antiphospholipid syndrome: Diagnosis and clinical manifestations (a lecture). 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The authors declare that there are no conflicts of interest present.