Preview

Obstetrics, Gynecology and Reproduction

Advanced search

Vaccine-induced immune thrombotic thrombocytopenia: definition, risks with different vaccines, and regulatory responses

https://doi.org/10.17749/2313-7347/ob.gyn.rep.2021.257

Full Text:

Abstract

After the vaccination campaign initiation in Europe and the UK, reports of rare cases of atypical thrombosis, including sinus vein thrombosis and splanchnic venous thrombosis, began to appear in association with the use of vector vaccines AstraZeneca (ChAdOx1) and Johnson & Johnson/Janssen. The syndrome called VITT (vaccine-induced immune thrombotic thrombocytopenia) manifested as thrombosis simultaneously with a decrease in platelet count, a significant increase in D-dimer levels and a detection of factor 4 platelet (PF4) antibodies. We present a detailed review of the epidemiology, pathogenesis, clinical presentation, diagnostics and treatment of VITT, which is by its nature an immune complication, similar to the processes occurring in heparin-induced thrombocytopenia (HIT). All international and national organizations and regulatory authorities, including experts in the field of thrombosis and hemostasis and the VITT expert council recommend continuing the prompt mass vaccination against COVID-19 as the only method that can reduce the incidence of severe cases, stop the spread of COVID-19 infection and the emergence of new dangerous mutations in the viral genome. Failure to vaccinate poses an incomparably greater risk of fatal thrombotic and inflammatory complications associated with infections, compared with the risks of extremely rare adverse events that can occur after vaccination. It should be noted that information on VITT, described as a sporadic phenomenon of an abnormal immune response to some variants of vaccines against COVID-19, cannot be translated to other vaccines (including registered in the Russian Federation) and even more cannot be a reason for refusal to use them.

About the Authors

S. V. Akinshina
«Medical Centre for Women» LLC
Russian Federation

Svetlana V. Akinshina – MD, PhD, Obstetrician-Gynecologist, Hematologist

62 Str. Zemlyanoi Val, Moscow 109004



V. O. Bitsadze
Sechenov University
Russian Federation

Victoria O. Bitsadze – MD, Dr Sci Med, Professor of RAS, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

Scopus Author ID: 6506003478

Researcher ID: F-8409-2017

 



J. Kh. Khizroeva
Sechenov University
Russian Federation

Jamilya Kh. Khizroeva – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

Scopus Author ID: 57194547147

Researcher ID: F-8384-2017

 



K. N. Grigorieva
Sechenov University
Russian Federation

Kristina N. Grigoreva – MD, Medical Resident, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991



E. V. Slukhanchuk
Sechenov University; Petrovsky National Research Centre of Surgery
Russian Federation

Ekaterina V. Slukhanchuk – MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health; Obstetrician-Gynecologist, Department of Abdominal Surgery and Oncology 2

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991;

2 Abrikosovskiy Lane, Moscow 119991



M. V. Tretyakova
«Medical Center» LLC
Russian Federation

Maria V. Tretyakova – MD, PhD, Obstetrician-Gynecologist, Department of Gynecology

15/1 Timura Frunze Str., Moscow 119021



V. I. Tsibizova
Almazov National Medical Research Centre, Health Ministry of Russian Federation
Russian Federation

Valentina I. Tsibizova – MD, PhD, Obstetrician-Gynecologist, Research Laboratory of Operative Gynecology, Institute of Perinatology and Pediatrics; Physician, Department of Functional and Ultrasound Diagnostics

2 Akkuratova Str., Saint Petersburg 197341



I. Elalamy
Sechenov University; Medicine Sorbonne University; Hospital Tenon
France

Ismail Elalamy – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health, Sechenov University; Professor, Medicine Sorbonne University, Paris, France; Director of Hematology, Department of Thrombosis Center, Hospital Tenon

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991;

2 Rue de l’École de Médecine, 75006 Paris;

4 Rue de la Chine, 75020 Paris

Scopus Author ID: 7003652413

Researcher ID: AAC-9695-2019

 



J.-C. Gris
Sechenov University; University of Montpellier
France

Jean-Christophe Gris – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health, Sechenov University, 
Moscow, Russia; University of Montpellier

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991;

163 Rue Auguste Broussonnet, Montpellier 34090

Researcher ID: AAA-2923-2019



B. Brenner
Rambam Academic Hospital
Israel

Binyamin Brenner – MD, Dr Sci Med, Professor, Director of the Hematology and Bone Marrow Transplantation Institute; Director of the Department of Internal Medicine

31096 Haifa, Aliya-ha-Shniya Str., 8



E. Grandone
Sechenov University; Research Center «Casa Sollievo della Sofferenza»
Italy

Elvira Grandone – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health, Sechenov University; Professor, Thrombosis and Haemostasis Research Unit, Department of Medical Genetics, Ospedale "Casa Sollievo della Sofferenza"

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991;

1 Viale Cappuccini, San Giovanni Rotondo 71013

Scopus Author ID: 7006391091. Researcher ID: M-1127-2019.

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991, Russia;

1 Viale Cappuccini, San Giovanni Rotondo 71013, Italia



C. Ay
University of Vienna
Austria

Cihan Ay – MD, PhD, Professor, Department of Medicine I, Clinical Division of Haematology and  Haemostaseology

1 Universitätsring, Vienna 1010

Scopus Author ID: 55356863800



A. D. Makatsariya
Sechenov University
Russian Federation

Alexander D. Makatsariya – MD, Dr Sci Med, Academician of RAS, Professor, Head of the Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

Scopus Author ID: 57222220144

Researcher ID: M-5660-2016

 



References

1. WHO Coronavirus (COVID-19) Dashboard. World Health Organization, 07 September 2021. Available at: https://covid.who.int. [Accessed: 07.09.2021].

2. Official information about the coronavirus in Russia, operational data, stopcoronavirus.rf. [Oficial'naya informaciya o koronaviruse v Rossii, operativnye dannye, stopkoronavirus.rf]. (In Russ.). Available at: https://xn--80aesfpebagmfblc0a.xn--p1ai/information/. [Accessed: 07.09.2021].

3. COVID-19 vaccine tracker and landscape. World Health Organization, 07 September 2021. Available at: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines . [Accessed: 07.09.2021].

4. 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.

5. AstraZeneca’s COVID-19 vaccine: EMA finds possible link to very rare cases of unusual blood clots with low blood platelets. News 07/04/2021. Available at: https://www.ema.europa.eu/en/news/astrazenecas-covid-19-vaccine-ema-finds-possible-link-very-rare-cases-unusual-blood-clots-low-blood. [Accessed: 07.09.2021].

6. Coronavirus vaccine – weekly summary of Yellow Card reporting. Available at: https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting . [Accessed: 07.09.2021].

7. Guidelines: diagnosis and management of thrombosis with thrombocytopenia syndrome (TTS) following adenovirus vectored COVID-19 vaccinations. 11 August 2021. 6 p. Available at: https://www.un.org/sites/un2.un.org/files/coronavirus_vipitguidance.pdf . [Accessed: 07.09.2021].

8. Press release. JCVI advises on COVID-19 vaccine for people aged under 40. The Joint Committee on Vaccination and Immunisation (JCVI) has issued advice to the UK government on the use of the coronavirus (COVID-19) Oxford/AstraZeneca vaccine for people aged under 40. Published 7 May 2021. Available at: https://www.gov.uk/government/news/jcvi-advises-on-covid-19-vaccine-for-people-aged-under-40 . [Accessed: 07.09.2021].

9. Elalamy I., Gerotziafas G., Alamowitch S. et al.; Scientific Reviewer Committee. SARS-CoV-2 vaccine and thrombosis: an expert consensus on vaccine-induced immune thrombotic thrombocytopenia. Thromb Haemost. 2021;121(8):982–91. https://doi.org/10.1055/a-1499-0119.

10. Selected Adverse Events Reported after COVID-19 Vaccination. Available at: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html . [Accessed: 07.09.2021].

11. Safety of COVID-19 Vaccines . Available at: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/safety-of-vaccines.html . [Accessed: 07.09.2021].

12. Guidelines: Diagnosis and Management of Thrombosis with Thrombocytopenia Syndrome (TTS) following Adenovirus Vectored COVID-19 Vaccinations. 11 August 2021. 6 p. Available at: https://www.un.org/sites/un2.un.org/files/coronavirus_vipitguidance.pdf . [Accessed: 07.09.2021].

13. Kuipers S., Cannegieter S.C., Middeldorp S. et al. The absolute risk of venous thrombosis after air travel: a cohort study of 8,755 employees of international organizations. PLoS Med. 2007;4(9):e290. https://doi.org/10.1371/journal.pmed.0040290.

14. Malas M.B., Naazie I.N., Elsayed N. et al. Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: A systematic review and meta-analysis. EClinicalMedicine. 2020;29:100639. https://doi.org/10.1016/j.eclinm.2020.100639.

15. Arepally G.M., Hursting M.J. Plateletfactor 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.

16. Heparin-Induced Thrombocytopenia. Eds. T.E. Warkentin, A. Greinacher. New York: Marcel Dekker Inc., 2000. 400 p.

17. Roberts В., Rosato F.E., Rosato E.F. Heparin: a cause of arterial emboli? Surgery. 1963;55:803–8.

18. Rhodes G.R., Dixon R.H., Silver D. Heparin induced thrombocytopenia with thrombotic and hemorrhagic manifestations. Surg Gynecol Obstet. 1973;136(3):409–16.

19. Harenberg J., Huhle G., Wang L. et al. Association of heparin-induced skin lesions, intracutaneous tests and heparin-induced IgG. Allergy. 1999;54(5):473–7. https://doi.org/10.1034/j.1398-9995.1999.00048.x.

20. Chong B.H., Berndt M.C. Heparin-induced thrombocytopenia. Blut. 1989;58(2):53–7. https://doi.org/10.1007/BF00320647.

21. Girolami B., Girolami A. Heparin-induced thrombocytopenia: a review. Semin Thromb Hemost. 2006;32(8):803–9. https://doi.org/10.1055/s-2006-955463.

22. 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.

23. 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.

24. Heparin-Induced Thrombocytopenia. Eds. T.E. Warkentin, A. Greinacher. New York: Marcel Dekker Inc., 2000. 400 p.

25. Warkentin T.E., Greinacher A. Spontaneous HIT syndrome: knee replacement, infection, and parallels with vaccine-induced immunethrombotic thrombocytopenia. Thromb Res. 2021;204:40–51. https://doi.org/10.1016/j.thromres.2021.05.018.

26. 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(1):53–64. https://doi.org/10.1160/TH13-08-0634.

27. Kasthuri R.S., Glover S.L., Jonas W. et al. PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI. Blood. 2012;119(22):5285–93. https://doi.org/10.1182/blood-2011-06-359430.

28. Jaax M.E., Krauel K., Marschall T. et al. Complex formation with nucleic acids and aptamers alters the antigenic properties of platelet factor 4. Blood. 2013;122(2):272–81. https://doi.org/10.1182/blood-2013-01-478966.

29. Greinacher A., Michels I., Schafer M. et al. Heparin associated thrombocytopenia in a patient treated with polysulphated chondroitin sulphate: evidence for immunological crossreactivity between heparin and polysulphated glycosaminoglycan. Br J Haematol. 1992;81(2):252–4. https://doi.org/10.1111/j.1365-2141.1992.tb08216.x.

30. Warkentin T.E., Makris M., Jay R.M., Kelton J.G. A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia. Am J Med. 2008;121(7):632–36. https://doi.org/10.1016/j.amjmed.2008.03.012.

31. Krauel K., Potschke C., Weber C. et al. Platelet factor 4 binds to bacteria, [corrected] inducing antibodies cross-reacting with the major antigen in heparin-induced thrombocytopenia. Blood. 2011;117(4):1370–8. https://doi.org/10.1182/blood-2010-08-301424.

32. Huynh A., Kelton J.G., Arnold D.M. et al. Antibody epitopes in vaccine-induced immune thrombotic thrombocytopaenia. Nature. 2021;596(7873):565–9. https://doi.org/10.1038/s41586-021-03744-4.

33. Huang C., Wang Y., Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. https://doi.org/10.1016/S0140-6736(20)30183-5.

34. Ruan Q., Yang K., Wang W. et al. Correction to: clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846–8. https://doi.org/10.1007/s00134-020-05991-x.

35. Wang D., Hu B., Hu C. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061–9. https://doi.org/10.1001/jama.2020.1585.

36. Guan W.J., Ni Z.Y., Hu Y. et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–20. https://doi.org/10.1056/NEJMoa2002032.

37. Wu C., Chen X., Cai Y. et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934–43. https://doi.org/10.1001/jamainternmed.2020.0994.

38. Zhou F., Yu T., Du R. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–62. https://doi.org/10.1016/S0140-6736(20)30566-3.

39. Lippi G., Plebani M., Henry B.M. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta. 2020;506:145–8. https://doi.org/10.1016/j.cca.2020.03.022.

40. Lovecchio F. Heparin-induced thrombocytopenia. Clin Toxicol (Phila). 2014;52(6):579–83. https://doi.org/10.3109/15563650.2014.917181.

41. Warkentin T.E., Aird W.C., Rand J.H. Platelet-endothelial interactions: sepsis, HIT, and antiphospholipid syndrome. Hematology Am Soc Hematol Educ Program. 2003:497–519. https://doi.org/10.1182/asheducation-2003.1.497.

42. Kravitz M.S., Shoenfeld Y. Thrombocytopenic conditions-autoimmunity and hypercoagulability: commonalities and differences in ITP, TTP, HIT, and APS. Am J Hematol. 2005;80(3):232–42. https://doi.org/10.1002/ajh.20408.

43. Chong B.H., Fawaz I., Chesterman C.N., Berndt M.C. Heparin-induced thrombocytopenia: mechanism of interaction of the heparin-dependent antibody with platelets. Br J Haematol. 1989;73(2):235–40. https://doi.org/10.1111/j.1365-2141.1989.tb00258.x.

44. Liu X., Zhang X., Xiao Y. et al. Heparin-induced thrombocytopenia is associated with a high risk of mortality in critical COVID-19 patients receiving heparin-involved treatment. medRxiv. April 28, 2020. https://doi.org/10.1101/2020.04.23.20076851. Available at: https://www.medrxiv.org/content/10.1101/2020.04.23.20076851v1.

45. Palankar R., Kohler T.P., Krauel K. et al. Platelets kill bacteria by bridging innate and adaptive immunity via platelet factor 4 and FcγRIIa. J Thromb Haemost. 2018;16(6):1187–97. https://doi.org/10.1111/jth.13955.

46. Krauel K., Pötschke C., Weber C. et al. Platelet factor 4 binds to bacteria, inducing antibodies cross-reacting with the major antigen in heparin-induced thrombocytopenia. Blood. 2011;117(4):1370–8. https://doi.org/10.1182/blood-2010-08-301424.

47. Warkentin Т.E., Anderson J.A.M. How I treat patients with a history of HIT. Blood. 2016;128(3):348–59. https://doi.org/10.1182/blood-2016-01-635003.

48. Hursting M.J., Pai P., McCracken J.E. et al. Platelet factor 4/heparin antibodies in blood bank donor. Am J Clin Pathol. 2010;134(5):774–80. https://doi.org/10.1309/AJCPG0MNR5NGKNFX.

49. 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.

50. Tiede A., Sachs U.J., Czwalinna A. et al. Prothrombotic immune thrombocytopenia after COVID-19 vaccination. Blood. 2021;138(4):350–3. https://doi.org/10.1182/blood.2021011958.

51. Thrombosis with Thrombocytopenia Syndrome (also termed Vaccine-induced Thrombotic Thrombocytopenia) (Version 1.6; last updated August 12, 2021). Input from Bussel J.B., Connors J.M., B.C. Douglas et al. Available at: https://www.hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia . [Accessed: 07.09.2021].

52. Logunov D.Y., Dolzhikova I.V., Shcheblyakov D.V. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet. 2021;397(10275):671–81. https://doi.org/10.1016/S0140-6736(21)00234-8.

53. Campaña Nacional de Vacunación contra la COVID-19. 12° Informe de vigilancia de seguridad en vacunas. Junio de 2021. 7 p. Available at: https://bancos.salud.gob.ar/recurso/12o-informe-de-vigilancia-de-seguridad-en-vacunas . [Accessed: 07.09.2021].

54. Official information about the coronavirus in Russia. The main thing about the coronavirus on September 7. stopcoronavirus.rf. [Oficial'naya informaciya o koronaviruse v Rossii. Glavnoe o koronaviruse za 7 sentyabrya. stopkoronavirus.rf]. Available at: https://xn--80aesfpebagmfblc0a.xn--p1ai/news/20210907-1908.html. [Accessed: 07.09.2021].

55. 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.


For citation:


Akinshina S.V., Bitsadze V.O., Khizroeva J.K., Grigorieva K.N., Slukhanchuk E.V., Tretyakova M.V., Tsibizova V.I., Elalamy I., Gris J., Brenner B., Grandone E., Ay C., Makatsariya A.D. Vaccine-induced immune thrombotic thrombocytopenia: definition, risks with different vaccines, and regulatory responses. Obstetrics, Gynecology and Reproduction. 2021;15(5):562-575. https://doi.org/10.17749/2313-7347/ob.gyn.rep.2021.257

Views: 371


ISSN 2313-7347 (Print)
ISSN 2500-3194 (Online)