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Immune paradoxes of vaccine-induced thrombotic thrombocytopenia (VITТ), heparin-induced thrombocytopenia (HIT) and thrombosis: from general mechanisms to the unique VITТ and HIT course

https://doi.org/10.17749/2313-7347/ob.gyn.rep.2025.610

Abstract

Aim: to carry out a comparative analysis of the pathogenesis, clinical manifestations, diagnostic criteria as well as therapeutic strategies of vaccine-induced thrombotic thrombocytopenia (VITТ) and heparin-induced thrombocytopenia (HIT), two rare but potentially life-threatening conditions associated with antibody-dependent platelet activation.

Materials and Methods. Current data on the pathogenesis, epidemiology, clinical presentation, diagnosis, and treatment of VITТ and HIT have been reviewed including an analysis of existing diagnostic scoring systems, laboratory tests, and therapeutic approaches. The study is based on the data obtained from systematic reviews, clinical studies, and up-to-date clinical guidelines.

Results. VITТ and HIT share a common pathophysiological mechanism involving the production of antibodies against platelet factor 4 (PF4) and subsequently developing thrombotic complications. However, a key difference lies in the triggers of the immune response: HIT is induced by heparin exposure, whereas VITТ develops following the administration of adenoviral vector vaccines against SARS-CoV-2. HIT is primarily characterized by venous thrombosis, while VITТ predominantly manifests with atypical thromboses, including cerebral venous sinus thrombosis. Both conditions require immediate medical intervention; however, HIT management involves discontinuation of heparin and the initiation of using alternative anticoagulants, whereas VITТ treatment requires administration of intravenous immunoglobulins and anticoagulants, including heparin-based agents.

Conclusion. Despite their rarity, VITТ and HIT pose significant health risks to patients. Modern diagnostic methods, including the 4Тs scoring system and serological testing, facilitate the timely identification of HIT, whereas VITТ diagnostics remains a complex challenge and requires further standardization. Optimizing therapeutic strategies, including the use of novel anticoagulants and immunosuppressive approaches, is a priority task to reduce mortality and improve patient outcomes.

About the Authors

A. D. Makatsariya
Sechenov University
Russian Federation

Alexander D. Makatsariya, MD, Dr Sci Med, Prof., Academician of RAS

Scopus Author ID: 57222220144

WoS ResearcherID: M-5660-2016

8 bldg. 2, Trubetskaya Str., Moscow 119991



S. V. Akinshina
Sechenov University
Russian Federation

Svetlana V. Akinshina, MD, PhD

Scopus Author ID: 15072687000

8 bldg. 2, Trubetskaya Str., Moscow 119991



A. V. Vorobev
Sechenov University
Russian Federation

Alexander V. Vorobev, MD, PhD

Scopus Author ID: 57191966265

Wos ResearcherID: F-8804-2017

8 bldg. 2, Trubetskaya Str., Moscow 119991



V. O. Bitsadze
Sechenov University
Russian Federation

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



J. Kh. Khizroeva
Sechenov University
Russian Federation

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

Scopus Author ID: 57194547147

WoS ResearcherID: F-8384-2017

8 bldg. 2, Trubetskaya Str., Moscow 119991



M. V. Tretyakova
Sechenov University
Russian Federation

Maria V. Tretyakova, MD, PhD

8 bldg. 2, Trubetskaya Str., Moscow 119991



N. A. Makatsariya
Sechenov University
Russian Federation

Nataliya A. Makatsariya, MD, PhD.

WoS ResearcherID: F-8406-2017

8 bldg. 2, Trubetskaya Str., Moscow 119991



I. S. Kalashnikova
Sechenov University
Russian Federation

Irina S. Kalashnikova, MD, PhD.

8 bldg. 2, Trubetskaya Str., Moscow 119991



N. R. Gashimova
Sechenov University
Russian Federation

Nilufar R. Gashimova, MD, PhD. 

8 bldg. 2, Trubetskaya Str., Moscow 119991



K. N. Grigoreva
Sechenov University
Russian Federation

Kristina N. Grigoreva, MD, PhD. 

8 bldg. 2, Trubetskaya Str., Moscow 119991



I. A. Stepanov
Sechenov University
Russian Federation

Ivan A. Stepanov

8 bldg. 2, Trubetskaya Str., Moscow 119991



I. M. Dikareva
Sechenov University
Russian Federation

Irina M. Dikareva

8 bldg. 2, Trubetskaya Str., Moscow 119991



A. Yu. Tatarintseva
Sechenov University
Russian Federation

Alena Yu. Tatarintseva

8 bldg. 2, Trubetskaya Str., Moscow 119991



A. V. Lazarchuk
Sechenov University
Russian Federation

Arina V. Lazarchuk

8 bldg. 2, Trubetskaya Str., Moscow 119991



A. R. Khisamieva
Sechenov University
Russian Federation

Azaliia R. Khisamieva

8 bldg. 2, Trubetskaya Str., Moscow 119991



D. V. Blinov
Institute for Preventive and Social Medicine; Moscow Haass Medical – Social Institute; Federal Scientific and Clinical Center for Medical Rehabilitation and Balneology, Federal Medical-Biological Agency
Russian Federation

Dmitry V. Blinov, MD, PhD, MBA.

Scopus Author ID: 6701744871

WoS ResearcherID: E-8906-2017

11–13/1 Lyalin Pereulok, Moscow 101000; 5 bldg. 1–1a, 2-ya Brestskaya Str., Moscow 123056; 6 bldg. 1, Rodnikovaya Str., Village Goluboe, Moscow region 141551



P. Van Dreden
Sorbonne University
France

Patrick Van Dreden, MD, Dr Sci Med, Prof.

Scopus Author ID: 55915955300

NSERM UМR_S_938, Paris



J.-Ch. Gris
Sechenov University; University of Montpellier
Russian Federation

Jean-Christophe Gris, MD, Dr Sci Med, Prof. 

Scopus Author ID: 7005114260

WoS ResearcherID: AAA-2923-2019

8 bldg. 2, Trubetskaya Str., Moscow 119991; 163 Rue Auguste Broussonnet, Montpellier 34090



I. Elalamy
Sechenov University; Medicine Sorbonne University; Hospital Tenon
Russian Federation

Ismail Elalamy, MD, Dr Sci Med, Prof.

Scopus Author ID: 7003652413

WoS ResearcherID: AAC-9695-2019

8 bldg. 2, Trubetskaya Str., Moscow 119991; 12 Rue de l’École de Médecine, Paris 75006; Hospital Tenon



G. Gerotziafas
Sechenov University; Medicine Sorbonne University; Hospital Tenon
Russian Federation

Grigoriоs Gerotziafas, MD, Dr Sci Med, Prof. 

8 bldg. 2, Trubetskaya Str., Moscow 119991; 12 Rue de l’École de Médecine, Paris 75006; 4 Rue de la Chine, Paris 75020



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What is already known about this subject?

► Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but severe immunological reaction associated with adenoviral vector-based COVID-19 vaccines.

► VITT is a potentially life-threatening complication characterized by the development of thromboses, predominantly in atypical locations such as the cerebral venous sinuses and mesenteric vessels in combination with severe thrombocytopenia.

► Heparin-induced thrombocytopenia (HIT) and VITT share a common pathophysiological mechanism involving production of anti-platelet factor 4 (PF4) antibodies and the subsequent development of thrombotic complications.

What are the new findings?

► The article provides a description of the pathogenesis of PF4-related platelet disorders including various HIT forms (classical, autoimmune, and spontaneous), as well as the VITT molecular mechanisms including spontaneous, non-vaccine-associated cases.

► Emerging evidence suggests that VITT may not be exclusive
to SARS-CoV-2 vaccines.

► The article outlines a diagnostic algorithm for the rapid identification of PF4-related platelet disorders; key differences in the pathogenesis and management strategies for VITT and HIT are reviewed.

How might it impact on clinical practice in the foreseeable future?

► Understanding VITT epidemiology and mechanisms is essential for guiding future research and ensuring vaccine safety.

► Optimizing therapeutic strategies, including the use of novel anticoagulants and immunosuppressive approaches, is a priority task to reduce mortality and improve outcomes in patients with VITT and HIT.

Review

For citations:


Makatsariya A.D., Akinshina S.V., Vorobev A.V., Bitsadze V.O., Khizroeva J.Kh., Tretyakova M.V., Makatsariya N.A., Kalashnikova I.S., Gashimova N.R., Grigoreva K.N., Stepanov I.A., Dikareva I.M., Tatarintseva A.Yu., Lazarchuk A.V., Khisamieva A.R., Blinov D.V., Van Dreden P., Gris J., Elalamy I., Gerotziafas G. Immune paradoxes of vaccine-induced thrombotic thrombocytopenia (VITТ), heparin-induced thrombocytopenia (HIT) and thrombosis: from general mechanisms to the unique VITТ and HIT course. Obstetrics, Gynecology and Reproduction. 2025;19(1):97-109. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2025.610

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