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Thrombosis in VEXAS syndrome

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Abstract

VEXAS syndrome, an autoinflammatory syndrome due to a Ubiquitin Like Modifier Activating Enzyme 1 (UBA1) somatic mutation, has a high thrombotic burden. We report a case of a 69-year-old male that was diagnosed with VEXAS syndrome who developed venous thromboembolism (VTE). Review of literature of existing VEXAS syndrome cases showed a high thrombotic burden, with the reported incidence of VTE (36.4%) being markedly higher than arterial thrombosis (1.6%), with deep vein thrombosis being more common than pulmonary embolism. Somatic mutation in the UBA1 gene results in decreased ubiquitylation which is a key driver in the development of thrombosis in VEXAS syndrome, due to chronic inflammation and cytokine release from abnormal crosstalk between the intrinsic effector mechanism of innate immune cells, platelets and endothelium resulting in dysregulated haemostasis and endothelial dysfunction. Targeting endothelial dysfunction and reducing inflammatory milieu causing hypercoagulability with immunosuppressants and immunomodulatory agents, together with anticoagulation may be the strategy to prevent recurrent thrombotic events.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Beck DB, Ferrada MA, Sikora KA et al (2020) Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med 383(27):2628–2638. https://doi.org/10.1056/NEJMoa20268342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fan BE, Cao L, Gallardo CA et al (2021) Myeloid and lymphoid vacuolation in VEXAS syndrome. Am J Hematol 96(8):1056–1057. https://doi.org/10.1002/ajh.26098

    Article  PubMed  Google Scholar 

  3. Georgin-Lavialle S, Terrier B, Guedon AF et al (2021) Further characterization of clinical and laboratory features occurring in VEXAS syndrome in a large-scale analysis of multicenter case-series of 116 French patients. Br J Dermatol. https://doi.org/10.1111/bjd.20805

    Article  PubMed  Google Scholar 

  4. Obiorah IE, Patel BA, Groarke EM et al (2021) Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1. Blood Adv 5(16):3203–3215. https://doi.org/10.1182/bloodadvances.2021004976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. van der Made CI, Potjewijd J, Hoogstins A et al (2021) Adult-onset autoinflammation caused by somatic mutations in UBA1: a Dutch case series of patients with VEXAS. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2021.05.014

    Article  PubMed  Google Scholar 

  6. Bourbon E, Heiblig M, Gerfaud Valentin M et al (2021) Therapeutic options in VEXAS syndrome: insights from a retrospective series. Blood 137(26):3682–3684. https://doi.org/10.1182/blood.2020010177

    Article  CAS  PubMed  Google Scholar 

  7. Poulter JA, Collins JC, Cargo C et al (2021) Novel somatic mutations in UBA1 as a cause of VEXAS syndrome. Blood 137(26):3676–3681. https://doi.org/10.1182/blood.2020010286

    Article  CAS  PubMed  Google Scholar 

  8. Tsuchida N, Kunishita Y, Uchiyama Y et al (2021) Pathogenic UBA1 variants associated with VEXAS syndrome in Japanese patients with relapsing polychondritis. Ann Rheum Dis. https://doi.org/10.1136/annrheumdis-2021-220089

    Article  PubMed  Google Scholar 

  9. Lacombe V, Prevost M, Bouvier A et al (2021) Vacuoles in neutrophil precursors in VEXAS syndrome: diagnostic performances and threshold. Br J Haematol. https://doi.org/10.1111/bjh.17679

    Article  PubMed  Google Scholar 

  10. Arlet JB, Terrier B, Kosmider O (2021) Mutant UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med 384(22):2163. https://doi.org/10.1056/NEJMc2102124

    Article  PubMed  Google Scholar 

  11. Barba T, Jamilloux Y, Durel CA et al (2021) VEXAS syndrome in a woman. Rheumatology (Oxford). https://doi.org/10.1093/rheumatology/keab392

    Article  Google Scholar 

  12. Ivanova EA, Orekhov AN (2016) The role of endoplasmic reticulum stress and unfolded protein response in atherosclerosis. Int J Mol Sci. 17(2):193. https://doi.org/10.3390/ijms17020193

    Article  CAS  PubMed Central  Google Scholar 

  13. Grey A, Cheong PL, Lee FJ et al (2021) A case of VEXAS syndrome complicated by hemophagocytic lymphohistiocytosis. J Clin Immunol 41(7):1648–1651. https://doi.org/10.1007/s10875-021-01070-y

    Article  PubMed  Google Scholar 

  14. Najem MY, Couturaud F, Lemarié CA (2020) Cytokine and chemokine regulation of venous thromboembolism. J Thromb Haemost 18(5):1009–1019

    Article  CAS  Google Scholar 

  15. McCormack JJ, Lopes da Silva M, Ferraro F, Patella F, Cutler DF (2017) Weibel-Palade bodies at a glance. J Cell Sci 130(21):3611–3617. https://doi.org/10.1242/jcs.208033

    Article  CAS  PubMed  Google Scholar 

  16. Engelmann B, Massberg S (2013) Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 13(1):34–45. https://doi.org/10.1038/nri3345

    Article  CAS  PubMed  Google Scholar 

  17. Borissoff JI, ten Cate H (2011) From neutrophil extracellular traps release to thrombosis: an overshooting host-defense mechanism? J Thromb Haemost 9(9):1791–1794. https://doi.org/10.1111/j.1538-7836.2011.04425.x

    Article  CAS  PubMed  Google Scholar 

  18. Rautou PE, Mackman N (2013) Microvesicles as risk markers for venous thrombosis. Expert Rev Hematol 6(1):91–101. https://doi.org/10.1586/ehm.12.74

    Article  CAS  PubMed  Google Scholar 

  19. Muratore F, Marvisi C, Castrignanò P et al (2021) VEXAS syndrome: a case series from a single-center cohort of Italian patients with vasculitis. Arthritis Rheumatol. https://doi.org/10.1002/art.41992

    Article  PubMed  Google Scholar 

  20. Meroni PL, Borghi MO, Raschi E, Tedesco F (2011) Pathogenesis of antiphospholipid syndrome: understanding the antibodies. Nat Rev Rheumatol 7(6):330–339

    Article  CAS  Google Scholar 

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Acknowledgements

The authors greatly appreciate the efforts of our fellow healthcare workers during this COVID-19 pandemic.

Funding

No funding was required for this study.

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Authors and Affiliations

  1. Department of General Medicine, Tan Tock Seng Hospital, Singapore, Singapore

    Thet Mon Oo & Siew Fen Lee

  2. Lee Kong Chian School of Medicine, Singapore, Singapore

    Thet Mon Oo, Shang Ming Samuel Lee, Xin Rong Lim & Bingwen Eugene Fan

  3. Yong Loo Lin School of Medicine, Singapore, Singapore

    Thet Mon Oo, Shang Ming Samuel Lee, Xin Rong Lim & Bingwen Eugene Fan

  4. Department of Haematology, Tan Tock Seng Hospital, 11 Jln Tan Tock Seng, Singapore, 308433, Singapore

    Jie Tian Jeanette Koay & Bingwen Eugene Fan

  5. Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore, Singapore

    Shang Ming Samuel Lee & Xin Rong Lim

  6. Department of Laboratory Medicine, Khoo Teck Puat Hospital, Singapore, Singapore

    Bingwen Eugene Fan

Authors
  1. Thet Mon Oo
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  2. Jie Tian Jeanette Koay
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  3. Siew Fen Lee
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  4. Shang Ming Samuel Lee
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  6. Bingwen Eugene Fan
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Contributions

BEF conceived the study. All authors contributed substantially to the acquisition, analysis and interpretation of data, critical revision of manuscript for important intellectual content.

Corresponding author

Correspondence to Bingwen Eugene Fan.

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Oo, T.M., Koay, J.T.J., Lee, S.F. et al. Thrombosis in VEXAS syndrome. J Thromb Thrombolysis 53, 965–970 (2022). https://doi.org/10.1007/s11239-021-02608-y

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  • DOI: https://doi.org/10.1007/s11239-021-02608-y

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