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. MakatsariyaRussian 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
Russian Federation
Svetlana V. Akinshina, MD, PhD
Scopus Author ID: 15072687000
8 bldg. 2, Trubetskaya Str., Moscow 119991
A. V. Vorobev
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
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
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
Russian Federation
Maria V. Tretyakova, MD, PhD
8 bldg. 2, Trubetskaya Str., Moscow 119991
N. A. Makatsariya
Russian Federation
Nataliya A. Makatsariya, MD, PhD.
WoS ResearcherID: F-8406-2017
8 bldg. 2, Trubetskaya Str., Moscow 119991
I. S. Kalashnikova
Russian Federation
Irina S. Kalashnikova, MD, PhD.
8 bldg. 2, Trubetskaya Str., Moscow 119991
N. R. Gashimova
Russian Federation
Nilufar R. Gashimova, MD, PhD.
8 bldg. 2, Trubetskaya Str., Moscow 119991
K. N. Grigoreva
Russian Federation
Kristina N. Grigoreva, MD, PhD.
8 bldg. 2, Trubetskaya Str., Moscow 119991
I. A. Stepanov
Russian Federation
Ivan A. Stepanov
8 bldg. 2, Trubetskaya Str., Moscow 119991
I. M. Dikareva
Russian Federation
Irina M. Dikareva
8 bldg. 2, Trubetskaya Str., Moscow 119991
A. Yu. Tatarintseva
Russian Federation
Alena Yu. Tatarintseva
8 bldg. 2, Trubetskaya Str., Moscow 119991
A. V. Lazarchuk
Russian Federation
Arina V. Lazarchuk
8 bldg. 2, Trubetskaya Str., Moscow 119991
A. R. Khisamieva
Russian Federation
Azaliia R. Khisamieva
8 bldg. 2, Trubetskaya Str., Moscow 119991
D. V. Blinov
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
France
Patrick Van Dreden, MD, Dr Sci Med, Prof.
Scopus Author ID: 55915955300
NSERM UМR_S_938, Paris
J.-Ch. Gris
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
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
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
References
1. Weismann R.E., Tobin R.W. Arterial embolism occurring during systemic heparin therapy. AMA Arch Surg. 1958;76(2):219–25. https://doi.org/10.1001/archsurg.1958.01280200041005.
2. May J., Cuker A. Practical guide to the diagnosis and management of heparin-induced thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2024;2024(1):388–95. https://doi.org/10.1182/hematology.2024000566.
3. Dhakal B., Kreuziger L.B., Rein L. et al. Disease burden, complication rates, and health-care costs of heparin-induced thrombocytopenia in the USA: a population-based study. Lancet Haematol. 2018;5(5):e220–e231. https://doi.org/10.1016/S2352-3026(18)30046-2.
4. Greinacher A., Farner B., Kroll H. et al. Clinical features of heparin-induced thrombocytopenia including risk factors for thrombosis. A retrospective analysis of 408 patients. Thromb Haemost. 2005;94(1):132–5. https://doi.org/10.1160/TH04-12-0825.
5. Warkentin T.E. New approaches to the diagnosis of heparin-induced thrombocytopenia. Chest. 2005;127(2 Suppl):35S–45S. https://doi.org/10.1378/chest.127.2_suppl.35S.
6. Greinacher A., Thiele T., Warkentin T.E. et al. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med. 2021;384(22):2092–101. https://doi.org/10.1056/NEJMoa2104840.
7. Scully M., Singh D., Lown R. et al. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination. N Engl J Med. 2021;384(23):2202–11. https://doi.org/10.1056/NEJMoa2105385.
8. Schultz N.H., Sørvoll I.H., Michelsen A.E. et al. Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination. N Engl J Med. 2021;384(22):2124–30. https://doi.org/10.1056/NEJMoa2104882.
9. Bhuyan P., Medin J., da Silva H.G. et al. Very rare thrombosis with thrombocytopenia after second AZD1222 dose: a global safety database analysis. Lancet. 2021;398(10300):577–8. https://doi.org/10.1016/S0140-6736(21)01693-7.
10. See I., Su J.R., Lale A. et al. US case reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, March 2 to April 21, 2021. JAMA. 2021;325(24):2448–56. https://doi.org/10.1001/jama.2021.7517.
11. Herrera-Comoglio R., Lane S. Vaccine-induced immune thrombocytopenia and thrombosis after the Sputnik V vaccine. N Engl J Med. 2022;387(15):1431–2. https://doi.org/10.1056/NEJMc2210813.
12. Martel N., Lee J., Wells P.S. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 2005;106(8):2710–5. https://doi.org/10.1182/blood-2005-04-1546.
13. Warkentin T.E., Levine M.N., Hirsh J. et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med. 1995;332(20):1330–5. https://doi.org/10.1056/NEJM199505183322003.
14. Othman M., Baker A.T., Gupalo E. et al. To clot or not to clot? Ad is the question – insights on mechanisms related to vaccine-induced thrombotic thrombocytopenia. J Thromb Haemost. 2021;19(11):2845–56. https://doi.org/10.1111/jth.15485.
15. Pavord S., Scully M., Hunt B.J. et al. Clinical features of vaccine-induced immune thrombocytopenia and thrombosis. N Engl J Med. 2021;385(18):1680–9. https://doi.org/10.1056/NEJMoa2109908.
16. Krzywicka K., van de Munckhof A., Zimmermann J. et al. Cerebral venous thrombosis due to vaccine-induced immune thrombotic thrombocytopenia after a second ChAdOx1 nCoV-19 dose. Blood. 2022;139(17):2720–4. https://doi.org/10.1182/blood.2021015329.
17. Favaloro E.J. Laboratory testing for suspected COVID-19 vaccine-induced (immune) thrombotic thrombocytopenia. Int J Lab Hematol. 2021;43(4):559–70. https://doi.org/10.1111/ijlh.13629.
18. Greinacher A., Langer F., Makris M. et al. Vaccine-induced immune thrombotic thrombocytopenia (VITT): Update on diagnosis and management considering different resources. J Thromb Haemost. 2022;20(1):149–56. https://doi.org/10.1111/jth.15572.
19. Kim A.Y., Woo W., Yon D.K. et al. Thrombosis patterns and clinical outcome of COVID-19 vaccine-induced immune thrombotic thrombocytopenia: a systematic review and meta-analysis. Int J Infect Dis. 2022;119:130–9. https://doi.org/10.1016/j.ijid.2022.03.034.
20. Arepally G.M. Heparin-induced thrombocytopenia. Blood. 2017;129(21):2864–72. https://doi.org/10.1182/blood-2016-11-709873.
21. Arepally G.M., Hursting M.J. Platelet factor 4/heparin antibody (IgG/M/A) in healthy subjects: a literature analysis of commercial immunoassay results. J Thromb Thrombolysis. 2008;26(1):55–61. https://doi.org/10.1007/s11239-008-0217-y.
22. Chan B.T., Bobos P., Odutayo A., Pai M. Meta-analysis of risk of vaccineinduced immune thrombotic thrombocytopenia following ChAdOx1-S recombinant vaccine. medRxiv. May 8, 2021. https://doi.org/10.1101/2021.05.04.21256613.
23. Klok F.A., Pai M., Huisman M.V, Makris M. Vaccine-induced immune thrombotic thrombocytopenia. Lancet Haematol. 2022;9(1):e73–e80. https://doi.org/10.1016/S2352-3026(21)00306-9.
24. Mingot-Castellano M.E., Butta N., Canaro M. et al. COVID-19 vaccines and autoimmune hematologic disorders. Vaccines. 2022;10(6):961. https://doi.org/10.3390/vaccines10060961.
25. Oliver S. Updates to the benefit/risk assessment for Janssen COVID-19 vaccines: Applying the Evidence to Recommendation Framework. ACIP Meeting, December 16, 2021. Available at: https://www.cdc.gov/vaccinesacip/meetings/downloads/slides-2021-12-16/04_covid_oliver_2021-12- 16.pdf. [Accessed: 10.01.2025].
26. Greinacher A., Schönborn L., Siegerist F. et al. Pathogenesis of vaccineinduced immune thrombotic thrombocytopenia (VITT). Semin Hematol. 2022;59(2):97–107. https://doi.org/10.1053/j.seminhematol.2022.02.004.
27. Warkentin T.E. How I diagnose and manage HIT. Hematology Am Soc Hematol Educ Program. 2011;2011(1):143–9. https://doi.org/10.1182/asheducation-2011.1.143.
28. Marchetti M., Zermatten M.G., Calderara D.B. et al. Heparin-induced thrombocytopenia: a review of new concepts in pathogenesis, diagnosis, and management. J Clin Med. 2021;10(4):683. https://doi.org/10.3390/jcm10040683.
29. Greinacher A., Holtfreter B., Krauel K. et al. Association of natural antiplatelet factor 4/heparin antibodies with periodontal disease. Blood. 2011;118(5):1395–401. https://doi.org/10.1182/blood-2011-03-342857.
30. Hursting M.J., Pai P.J., McCracken J.E. et al. Platelet factor 4/heparin antibodies in blood bank donors. Am J Clin Pathol. 2010;134(5):774–80. https://doi.org/10.1309/AJCPG0MNR5NGKNFX.
31. Brandt S., Krauel K., Gottschalk K.E. et al. Characterisation of the conformational changes in platelet factor 4 induced by polyanions: towards in vitro prediction of antigenicity. Thromb Haemost. 2014;112(7):53–64. https://doi.org/10.1160/TH13-08-0634.
32. Napolitano A., Spiezia L., Biolo M. et al. Anti-platelet factor 4 antibodymediated disorders: an updated narrative review. Semin Thromb Hemost. 2025, Jan 30. https://doi.org/10.1055/a-2528-5425. Online ahead of print.
33. Warkentin T.E. Platelet-activating anti-PF4 disorders: an overview. Semin Hematol. 2022;59(2):59–71. https://doi.org/10.1053/j.seminhematol.2022.02.005.
34. Favaloro E.J., Pasalic L., Henry B., Lippi G. Laboratory testing for platelet factor 4 antibodies: differential utility for diagnosis/exclusion of heparin induced thrombocytopenia versus suspected vaccine induced thrombotic thrombocytopenia. Pathology. 2022;54(3):254–61. https://doi.org/10.1016/j.pathol.2021.10.008.
35. Warkentin T.E., Greinacher A. Laboratory testing for heparin-induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia antibodies: a narrative review. Semin Thromb Hemost. 2022;49(6):621–33. https://doi.org/10.1055/s-0042-1758818.
36. Samuelson Bannow B., Warad D.M., Jones C.G. et al. A prospective, blinded study of a PF4-dependent assay for HIT diagnosis. Blood. 2021;137(8):1082–9. https://doi.org/10.1182/blood.2020008195.
37. Husseinzadeh H.D., Gimotty P.A., Pishko A.M. et al. Diagnostic accuracy of IgG-specific versus polyspecific enzyme-linked immunoassays in heparininduced thrombocytopenia: a systematic review and meta-analysis. J Thromb Haemost. 2017;15(6):1203–12. https://doi.org/10.1111/jth.13692.
38. Handtke S., Wolff M., Zaninetti C. et al. A flow cytometric assay to detect platelet activating antibodies in VITT after ChAdOx1 nCov-19 vaccination. Blood. 2021;137(26):3656–9. https://doi.org/10.1182/blood.2021012064.
39. Huynh A., Kelton J.G., Arnold D.M. et al. Antibody epitopes in vaccineinduced immune thrombotic thrombocytopaenia. Nature. 2021;596(7873):565–9. https://doi.org/10.1038/s41586-021-03744-4.
40. Brown J.A., Aranda-Michel E., Kilic A. et al. Outcomes with heparininduced thrombocytopenia after cardiac surgery. Ann Thorac Surg. 2021;112(2):487–93. https://doi.org/10.1016/j.athoracsur.2020.10.046.
41. Warkentin T.E. Autoimmune heparin-induced thrombocytopenia. J Clin Med. 2023;12(21):6921. https://doi.org/10.3390/jcm12216921.
42. Greinacher A., Selleng K., Warkentin T.E. Autoimmune heparin-induced thrombocytopenia. J Thromb Haemost. 2017;15(11):2099–114. https://doi.org/10.1111/jth.13813.
43. Manji F., Warkentin T.E, Sheppard J.-A.I., Lee A. Fondaparinux crossreactivity in heparininduced thrombocytopenia successfully treated with high-dose intravenous immunoglobulin and rivaroxaban. Platelets. 2020;31(1):124–7. https://doi.org/10.1080/09537104.2019.1652263.
44. Warkentin T.E., Greinacher A. Spontaneous HIT syndrome: knee replacement, infection, and parallels with vaccine-induced immune thrombotic thrombocytopenia. Thromb Res. 2021;204:40–51. https://doi.org/10.1016/j.thromres.2021.05.018.
45. Warkentin T.E., Makris M., Jay R.M., Kelton J.G. A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia. Am J Med. 208;121(7):632–6. https://doi.org/10.1016/j.amjmed.2008.03.012.
46. Krauel K., Pötschke C., Weber C. et al. Platelet factor 4 binds to bacteria, inducing antibodies cross-reacting with the major antigen in heparininduced thrombocytopenia. Blood. 2011;117(4):1370–8. https://doi.org/10.1182/blood-2010-08-301424.
47. Pai M. Epidemiology of VITT. Semin Hematol. 2022;59(2):72–5. https://doi.org/10.1053/j.seminhematol.2022.02.002.
48. Craven B., Lester W., Boyce S. et al. Natural history of PF4 antibodies in vaccine-induced immune thrombocytopenia and thrombosis. Blood. 2022;139(16):2553–60. https://doi.org/10.1182/blood.2021014684.
49. McGonagle D., De Marco G., Bridgewood C. Mechanisms of immunothrombosis in vaccine-induced thrombotic thrombocytopenia (VITT) compared to natural SARS-CoV-2 infection. J Autoimmun. 2021;121:102662. https://doi.org/10.1016/j.jaut.2021.102662.
50. Selvadurai M.V., Favaloro E.J., Chen V.M. Mechanisms of thrombosis in heparin-induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia. Semin Thromb Hemost. 2023;49(5):444–52. https://doi.org/10.1055/s-0043-1761269.
51. Greinacher A., Selleng K., Mayerle J. et al.; Immune-Response in COVID19 Vaccination Study Group. Anti-platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein. Blood. 2021;138(14):1269–77. https://doi.org/10.1182/blood.2021012938.
52. Nand S., Wong W., Yuen B. et al. Heparin-induced thrombocytopenia with thrombosis: incidence, analysis of risk factors, and clinical outcomes in 108 consecutive patients treated at a single institution. Am J Hematol. 1997;56(1):12–6. https://doi.org/10.1002/(sici)1096-8652(199709)56:13.0.co;2-5.
53. Cuker A., Gimotty P.A., Crowther M.A., Warkentin T.E. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood. 2012;120(20):4160–7. https://doi.org/10.1182/blood-2012-07-443051.
54. May J., Westbrook B., Cuker A. Heparin-induced thrombocytopenia: an illustrated review. Res Pract Thromb Haemost. 2023;7(5):100283. https://doi.org/10.1016/j.rpth.2023.100283.
55. Rogers P., Walker I., Yeung J. et al; RADIANT Group. Thrombus distribution in vaccine-induced immune thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. Radiology. 2022; 305(3):590–6. https://doi.org/10.1148/radiol.220365.
56. Schönborn L., Pavord S., Chen V.M.Y. et al. Thrombosis with thrombocytopenia syndrome (TTS) and vaccine-induced immune thrombocytopenia and thrombosis (VITT): Brighton Collaboration case definitions and guidelines for data collection, analysis, and presentation of immunisation safety data. Vaccine. 2024;42(7):1799–811. https://doi.org/10.1016/j.vaccine.2024.01.045.
57. Cuker A., Arepally G.M., Chong B.H. et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018;2(22):3360–92. https://doi.org/10.1182/bloodadvances.2018024489.
58. Gruel Y., De Maistre E., Pouplard C. et al. Diagnosis and management of heparin-induced thrombocytopenia. Anaesth Crit Care Pain Med. 2020;39(2):291–310. https://doi.org/10.1016/j.accpm.2020.03.012.
59. Pavord S., Hunt B.J., Horner D. et al. Vaccine induced immune thrombocytopenia and thrombosis: summary of NICE guidance. BMJ. 2021;375:n2195. https://doi.org/10.1136/bmj.n2195.
60. Müller L., Dabbiru V.A.S., Schönborn L., Greinacher A. Therapeutic strategies in FcγIIA receptor-dependent thrombosis and thromboinflammation as seen in heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytopenia and thrombosis (VITT). Expert Opin Pharmacother. 2024;25(3):281–94. https://doi.org/10.1080/14656566.2024.2328241.
61. Farner B., Eichler P., Kroll H. et al. A comparison of danaparoid and lepirudin in heparin-induced thrombocytopenia. Thromb Haemost. 2001;85(6):950–7. https://doi.org/10.1055/s-0037-1615946.
62. Fathi M. Heparin-induced thrombocytopenia (HIT): identification and treatment pathways. Glob Cardiol Sci Pract. 2018;2018(2):15. https://doi.org/10.21542/gcsp.2018.15.
63. Nilius H., Kaufmann J., Cuker A. et al. Comparative effectiveness and safety of anticoagulants for the treatment of heparin-induced thrombocytopenia. Am J Hematol. 2021;96(7):805–15. https://doi.org/10.1002/ajh.26194.
64. Warkentin T.E., Kelton J.G. A 14-year study of heparin-induced thrombocytopenia. Am J Med. 1996;101(5):502–7. https://doi.org/10.1016/S0002-9343(96)00258-6.
65. Schulman S., Arnold D.M., Bradbury C.A. et al. 2023 ISTH update of the 2022 ISTH guidelines for antithrombotic treatment in COVID-19. J Thromb Haemost. 2024;22(6);1779–97. https://doi.org/10.1016/j.jtha.2024.02.011.
66. Warkentin T.E., Pai M., Linkins L.-A. Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review. Blood. 2017;130(9):1104–13. https://doi.org/10.1182/blood-201704-778993.
67. Salih F., Schönborn L., Kohler S. et al. Vaccine-induced thrombocytopenia with severe headache. N Engl J Med. 2021;385(22):2103–5. https://doi.org/10.1056/NEJMc2112974.
68. Kreimann M., Brandt S., Krauel K. et al. Binding of anti-platelet factor 4/ heparin antibodies depends on the thermodynamics of conformational changes in platelet factor 4. Blood. 2014;124(15):2442–9. https://doi.org/10.1182/blood-2014-03-559518.
69. Nguyen T.-H., Greinacher A., Delcea M. Quantitative description of thermodynamic and kinetic properties of the platelet factor 4/heparin bonds. Nanoscale. 2015;7(22):10130–9. https://doi.org/10.1039/C5NR02132D.
70. Savi P., Chong B.H., Greinacher A. et al. Effect of fondaparinux on platelet activation in the presence of heparin-dependent antibodies: a blinded comparative multicenter study with unfractionated heparin. Blood. 2005;105(1):139–44. https://doi.org/10.1182/blood-2004-052010.
71. Linkins L.-.A, Hu G., Warkentin T.E. Systematic review of fondaparinux for heparin-induced thrombocytopenia: when there are no randomized controlled trials. Res Pract Thromb Haemost. 2018;2(4):678–83. https://doi.org/10.1002/rth2.12145.
72. Guidance for clinical case management of thrombosis with thrombocytopenia syndrome (TTS) following vaccination to prevent coronavirus disease (COVID-19). Geneva: World Health Organization, 2023. Available at: https://www.who.int/publications/i/item/9789240061989. [Accessed: 10.01.2025].
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

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.