Genetic predisposition to vaccine-induced immune thrombotic thrombocytopenia: is there a family link?
  • Rita Pombal
    Immunohemotherapy Department, Unidade Local de Saúde Gaia/Espinho, Vila Nova de Gaia, Portugal
  • Luciana Silva
    Internal Medicine Department, Unidade Local de Saúde Gaia/Espinho, Vila Nova de Gaia, Portugal
  • David Ferreira
    Immunohemotherapy Department, Unidade Local de Saúde Gaia/Espinho, Vila Nova de Gaia, Portugal

Keywords

COVID-19 vaccines, genetic predisposition to disease, purpura, thrombocytopenic, idiopathic, thrombocytopenia

Abstract

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare life-threatening thrombotic reaction to COVID-19 vaccines.
Case description: Two young male first cousins, with a family history of idiopathic thrombocytopenic purpura, developed VITT after the Ad26.COV2.S vaccine. Both had a favourable clinical and analytical outcome. We investigated the genetic factors that could be associated with a genetic predisposition to VITT.
Conclusions: There are no published cases where the VITT patients were relatives. The genetic study did not reveal any likely pathogenic variants, although the prevalent polymorphism c.497A>G (p.(His166Arg)) in the FCGR2A gene was found in a homozygous state. More studies are required to better understand VITT’s pathophysiology and any underlying genetic predispositions.

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References

  • Price-Haywood EG, Burton J, Fort D, Seoane L. Hospitalization and mortality among black patients and white patients with COVID-19. N Engl J Med 2020;382:2534–2543.
  • Hodgson SH, Mansatta K, Mallett G, Harris V, Emary KRW, Pollard AJ. What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2. Lancet Infect Dis 2021;21:e26-e35.
  • Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med 2021;384:2092–2101.
  • See I, Su JR, Lale A, Woo EJ, Guh AY, Shimabukuro TT, 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;325:2448–2456.
  • Makris M, Pavord S, Lester W, Scully M, Hunt B. Vaccine-induced immune thrombocytopenia and thrombosis (VITT). Res Pract Thromb Haemost 2021;5:e12529. Erratum in: Res Pract Thromb Haemost 2021;10;5:e12585.
  • Cines DB, Greinacher A. Vaccine-induced immune thrombotic thrombocytopenia. Blood 2023;141:1659–1665.
  • Nazy I, Sachs UJ, Arnold DM, McKenzie SE, Choi P, Althaus K, et al. Recommendations for the clinical and laboratory diagnosis of VITT against COVID-19: communication from the ISTH SSC Subcommittee on Platelet Immunology. J Thromb Haemost 2021;19:1585–1588.
  • nice.org.uk: COVID-19 rapid guideline: vaccine-induced immune thrombocytopenia and thrombosis (VITT). London: National Institute for Health and Care Excellence (NICE); 2022 Jun 22. https://www.nice.org.uk/guidance/ng200.
  • Greinacher A, Langer F, Makris M, Pai M, Pavord S, Tran H, et al. Vaccine-induced immune thrombotic thrombocytopenia (VITT): update on diagnosis and management considering different resources. J Thromb Haemost 2022;20:149–156.
  • ecdc.europa.eu: European Centre for Disease Prevention and Control. COVID-19 Vaccine Tracker [Internet]. c2023 [cited 2023 Dec 01]. Available from: https://vaccinetracker.ecdc.europa.eu/public/extensions/COVID-19/vaccine-tracker.html#uptake-tab.
  • Greinacher A, Selleng K, Palankar R, Wesche J, Handtke S, Wolff M, et al. Insights in ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopenia. Blood 2021;138:2256–2268.
  • Pavord S, Scully M, Hunt BJ, Lester W, Bagot C, Craven B, et al. Clinical features of vaccine-induced immune thrombocytopenia and thrombosis. N Engl J Med 2021;385:1680–1689.
  • Lombardi AM, Pulini S, Passeri C, Iuliani O, Salutari P, Businaro A, et al. Familial acquired thrombotic thrombocytopenic purpura: immunogenetic link with HLA-DRB1*11 and DQB1*03 antigens. Br J Haematol 2018;183:317–319.
  • Karnes JH. Pharmacogenetics to prevent heparin-induced thrombocytopenia: what do we know? Pharmacogenomics 2018;19:1413–1422.
  • Wang D, Hu SL, Cheng XL, Yang JY. FCGR2A rs1801274 polymorphism is associated with risk of childhood-onset idiopathic (immune) thrombocytopenic purpura: evidence from a meta-analysis. Thromb Res 2014;134:1323–1327.
  • Giles JB, Miller EC, Steiner HE, Karnes JH. Elucidation of cellular contributions to heparin-induced thrombocytopenia using omic approaches. Front Pharmacol 2022;12:812830.
  • Li G, Gao L, Ma R, Tian W, Mingzhi L. Associations between FCGR polymorphisms and immune thrombocytopenia: a meta-analysis. Scand J Immunol 2019;89:e12758.
  • Schmidt DE, Heitink-Pollé KMJ, Laarhoven AG, Bruin MCA, Veldhuisen B, Nagelkerke SQ, et al. Transient and chronic childhood immune thrombocytopenia are distinctly affected by Fc-y receptor polymorphisms. Blood Adv 2019;3:2003–2012.
  • Mendes-de-Almeida DP, Kehdy FSG, Martins-Goncalves R, Bokel J, Grinsztejn E, Mouta Nunes de Oliveira P, et al. A case report of vaccine-induced immune thrombotic thrombocytopenia (VITT) with genetic analysis. Front Cardiovasc Med 2023;10:1189320.
  • ad.broadinstitute.org: Genome Aggregation Database (gnomAD) [Internet]. c2023 [cited 2023 14 Dec] Available from: https://gnomad.broadinstitute.org/.

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    Published: 2024-05-14
    Issue: 2024: Vol 11 No 6 (view)

    How to cite:
    1.
    Pombal R, Silva L, Ferreira D. Genetic predisposition to vaccine-induced immune thrombotic thrombocytopenia: is there a family link?. EJCRIM 2024;11 doi:10.12890/2024_004546.

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