safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2025-13-2-149-160safetyrisk-465Research ArticleГЛАВНАЯ ТЕМА: ОЦЕНКА РИСКОВ И БЕЗОПАСНОСТЬ ФАРМАКОТЕРАПИИ В ГЕРОНТОЛОГИИ И ОСОБЫХ КЛИНИЧЕСКИХ СИТУАЦИЯХMAIN TOPIC: RISK ASSESSMENT AND SAFETY OF PHARMACOTHERAPY IN GERONTOLOGY AND SPECIAL CLINICAL CONDITIONSТромбоцитопения как побочный эффект гепаринотерапии и вакцинации против COVID-19: обзорThrombocytopenia as a Side Effect of Heparin Therapy and COVID-19 Vaccination: A Reviewhttps://orcid.org/0000-0001-8468-6959ПостниковС. С.PostnikovS. S.

Постников Сергей Сергеевич, д-р мед. наук, профессор

ул. Островитянова, д. 1, Москва, 117997

Sergey S. Postnikov, Dr. Sci. (Med.), Professor

1 Ostrovityanov St., Moscow 117513, Russian Federation

clinpharm@rambler.ruhttps://orcid.org/0000-0003-4259-0945ТепловаН. В.TeplovaN. V.

Теплова Наталья Вадимовна, д-р мед. наук, профессор

ул. Островитянова, д. 1, Москва, 117997

Natalia V. Teplova, Dr. Sci. (Med.), Professor

1 Ostrovityanov St., Moscow 117513, Russian Federation

teplova.nv@yandex.ruhttps://orcid.org/0000-0002-7412-3180ГульбековаО. В.GulbekovaO. V.

Гульбекова Олеся Владимировна

ул. Островитянова, д. 1, Москва, 117997

Olesya V. Gulbekova

1 Ostrovityanov St., Moscow 117513, Russian Federation

gulbekova1990@mail.ruФедеральное государственное автономное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской ФедерацииРоссияPirogov Russian National Research Medical UniversityRussian Federation202524062025132149160Copyright © Постников С.С., Теплова Н.В., Гульбекова О.В., 20252025Постников С.С., Теплова Н.В., Гульбекова О.В.Postnikov S.S., Teplova N.V., Gulbekova O.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/465

ВВЕДЕНИЕ. Частое использование гепарина, как низкомолекулярного, так и нефракционированного, для профилактики и лечения тромбозов, вызванных COVID-19, увеличивает риск возникновения такой нежелательной реакции, как гепарин-индуцированная тромбоцитопения (ГИТ). Вакцинация играет ключевую роль в борьбе с пандемией COVID-19, однако необходимо учитывать возможные побочные эффекты, в  частности, развитие после введения аденовирусных вакцин вакцино-индуцированной иммунной тромботической тромбоцитопении (ВИТТ).ЦЕЛЬ. Провести сравнительный анализ распространенности, патогенетических механизмов развития, особенностей проявления и лечения ГИТ и ВИТТ с целью выявления общих черт и различий данных нежелательных реакций, а также для оптимизации и выбора наиболее эффективной терапевтической стратегии для каждой из них в клинической практике.ОБСУЖДЕНИЕ. В анализ были включены полнотекстовые статьи на русском и английском языках следующих типов: систематические обзоры, метаанализы, клинические исследования, обзорные статьи, клинические случаи, опубликованные с 1992 по март 2024 г. и размещенные в библиографических базах данных PubMed, Lens.org, eLIBRARY.RU. Показано, что ГИТ чаще встречается у женщин, подвергшихся хирургическим вмешательствам на сердечно-сосудистой системе, ортопедическим операциям, находящихся на экстракорпоральной мембранной оксигенации; у пациентов с COVID-19 в критическом состоянии. ВИТТ более распространена среди женщин в возрасте до 55 лет, принимающих оральные контрацептивы, вакцинированных аденовирусной вакциной. ГИТ начинает проявляться приблизительно через 5–10 суток после начала применения гепарина, время начала ВИТТ варьирует от 4-х суток до 1 месяца. Для ВИТТ характерна атипичная локализация тромбозов в отличие от ГИТ. При ГИТ активирующие тромбоциты антитела IgG к PF4-гепарину связываются с рецепторами FcγRIIA, что приводит к активации и агрегации тромбоцитов. При ВИТТ полианионом, запускающим иммунную систему, является ДНК векторного аденовируса из внеклеточных ловушек нейтрофилов либо белок гексон. В качестве терапии ГИТ рассматривается прекращение применения гепарина либо переход с нефракционированного гепарина на низкомолекулярный или фондапаринукс натрия, негепариновые антикоагулянты (прямые ингибиторы тромбина, пероральные антикоагулянты). Вариантами лечения ВИТТ являются негепариновые антикоагулянты (переход на них необязателен), фондапаринукс натрия, внутривенное введение иммуноглобулинов. При обеих нежелательных реакциях основной причиной летального исхода является венозный тромбоз. ВЫВОДЫ. У медицинских работников должна быть настороженность в отношении возможного развития ВИТТ после вакцинации аденовирусными вакцинами против COVID-19 и ГИТ при применении гепарина, а пациентам с подозрением на указанные нежелательные реакции должны быть обеспечены неотложная госпитализация, консультация гематолога, лабораторное и инструментальное обследование.

INTRODUCTION. Both low-molecular-weight and unfractionated heparins are frequently used to prevent and treat COVID-19-associated thrombosis, placing patients at an increased risk of developing heparin-induced thrombocytopenia (HIT) as an adverse reaction. Vaccination has played a key role in combating the COVID-19 pandemic, yet careful consideration is needed for potential adverse events following immunisation, in particular, for vaccine-induced immune thrombotic thrombocytopenia (VITT) associated with adenoviral vector vaccines.AIM. This study aimed to conduct a comparative analysis of HIT and VITT prevalence, pathogenetic mechanisms, clinical manifestation patterns, and treatment considerations in order to select the most effective therapeutic strategies for each condition and optimise them for clinical use.DISCUSSION. This comparative analysis covers full-text systematic reviews, meta-analyses, clinical trial reports, review articles, and case reports in Russian and English published from 1992 to March 2024 and retrieved from bibliographic databases, including PubMed.gov, Lens.org, and eLIBRARY.RU. According to the analysis, HIT incidence is higher in women who had previous cardiovascular or orthopaedic surgery, women on extracorporeal membrane oxygenation, and critically ill patients with COVID-19, whereas VITT is more common in women under 55 taking oral contraceptives and immunised with an adenoviral vector vaccine. The first signs of HIT usually show 5–10 days after heparin initiation, and the time of VITT onset varies from 4 days to 1 month. In contrast to HIT, VITT is characterised by atypical localisation of thrombosis. In HIT, platelet-activating anti-heparin/platelet factor 4 IgG antibodies bind to FcγRIIA receptors, which leads to platelet activation and aggregation. In VITT, the polyanion that triggers the immune system is either hexon protein or adenoviral vector DNA from neutrophil extracellular traps. Potential treatments for HIT include heparin discontinuation or switching from unfractionated heparins to low-molecular-weight heparins, fondaparinux sodium, or non-heparin anticoagulants (direct thrombin inhibitors and oral anticoagulants). Treatment options for VITT include non-heparin anticoagulants, fondaparinux sodium, and intravenous immunoglobulins. Switching to non-heparin anticoagulants in VITT is optional. Venous thrombosis is the main cause of death in both adverse reactions.CONCLUSIONS. Medical professionals should be alert to the potential development of VITT after vaccination with adenoviral COVID-19 vaccines and HIT during the use of heparins. Patients with suspected adverse reactions require prompt hospital admission, haematologist consultation, and laboratory and instrument testing.

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