Skip to main content

Advertisement

SpringerLink
Log in

Response to belimumab in thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus: a case-based review

  • Case Based Review
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Thrombotic thrombocytopenic purpura (TTP), a life-threatening syndrome characterized by acute microangiopathic hemolytic anemia, thrombocytopenia, and visceral ischemia, can be classified as congenital TTP (inherited due to a mutation in ADAMTS13) and acquired TTP. The acquired TTP is further classified as idiopathic and secondary TTP. Systemic lupus erythematosus (SLE) is regarded as one of the most common causes of secondary TTP (SLE-TTP). In contrast to patients with idiopathic TTP, some patients with SLE-TTP, especially those diagnosed with refractory TTP, are resistant to plasma exchange and high-dose corticosteroids and usually require second-line drugs, including newly developed biologicals. Belimumab, a B-lymphocyte stimulator-specific inhibitor, was the first approved new therapy for SLE in the past 50 years. Only two cases of SLE-TTP using belimumab have been reported; however, detailed information has not been made available. Herein, we describe a 28-year-old female patient who presented with palm petechiae, strong tawny urine, and yellow stained skin and sclera, and was diagnosed with SLE-TTP supported by high anti-ANA titers; positive anti-SSA/SM; pleural effusion; decreased platelet count, hemoglobin, and complement C3/C4 counts; increased lactate dehydrogenase level, along with increased schistocytes; and a significant deficiency of ADAMTS13 activity. Belimumab (10 mg/kg) was administered after six plasma exchanges. Good efficiency and outcomes without any adverse events, SLE, or TTP relapse were observed during 12 months of follow-up. Therefore, belimumab is a promising choice for SLE-TTP management. In addition, we provide a focused review of the existing literature on the pathogenesis, diagnosis, and therapeutic strategies for SLE-TTP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

All data analyzed in this study are available from the first or corresponding authors upon reasonable request.

Written informed consent was obtained from the patient for the publication of this report and related clinical images.

References

  1. Joly BS, Coppo P, Veyradier A (2017) Thrombotic thrombocytopenic purpura. Blood 129:2836–2846. https://doi.org/10.1182/blood-2016-10-709857

    Article  CAS  PubMed  Google Scholar 

  2. Bhandari S, Kumar R (2019) Thrombotic thrombocytopenic purpura. N Engl J Med 380:e23. https://doi.org/10.1056/NEJMicm1813768

    Article  PubMed  Google Scholar 

  3. Laghmouchi A, Graca N, Voorberg J (2021) Emerging concepts in immune thrombotic thrombocytopenic purpura. Front Immunol 12:757192. https://doi.org/10.3389/fimmu.2021.757192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Durcan L, O’Dwyer T, Petri M (2019) Management strategies and future directions for systemic lupus erythematosus in adults. Lancet 393:2332–2343. https://doi.org/10.1016/S0140-6736(19)30237-5

    Article  PubMed  Google Scholar 

  5. Letchumanan P, Ng HJ, Lee LH, Thumboo JA (2009) Comparison of thrombotic thrombocytopenic purpura in an inception cohort of patients with and without systemic lupus erythematosus. Rheumatology (Oxford) 48:399–403. https://doi.org/10.1093/rheumatology/ken510

    Article  Google Scholar 

  6. Kwok SK, Ju JH, Cho CS, Kim HY, Park SH (2009) Thrombotic thrombocytopenic purpura in systemic lupus erythematosus: risk factors and clinical outcome: a single centre study. Lupus 18:16–21. https://doi.org/10.1177/0961203308094360

    Article  CAS  PubMed  Google Scholar 

  7. Yue C, Su J, Fan X, Song L, Jiang W, Xia J, Shi T, Zhang X, Li X (2020) Immune-mediated thrombotic thrombocytopenic purpura in patients with and without systemic lupus erythematosus: a retrospective study. Orphanet J Rare Dis 15:225. https://doi.org/10.1186/s13023-020-01510-9

    Article  PubMed  PubMed Central  Google Scholar 

  8. Abu-Hishmeh M, Sattar A, Zarlasht F, Ramadan M, Abdel-Rahman A, Hinson S, Hwang C (2016) Systemic lupus erythematosus presenting as refractory thrombotic thrombocytopenic purpura: a diagnostic and management challenge. A case report and concise review of the literature. Am J Case Rep 17:782–787. https://doi.org/10.12659/ajcr.898955

    Article  PubMed  PubMed Central  Google Scholar 

  9. Li J, Jiang JJ, Wang CY, Jian S, Zhou Y, Ma MS, Tang XY, Wang L, Quan MY, Zhang Y, Xiao J, He YY, Song HM (2019) Clinical features and prognosis of patients with thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus: a review of 25 cases. Ital J Pediatr 45:55. https://doi.org/10.1186/s13052-019-0641-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mazepa MA, Masias C, Chaturvedi S (2019) How targeted therapy disrupts the treatment paradigm for acquired TTP: the risks, benefits, and unknowns. Blood 134:415–420. https://doi.org/10.1182/blood.2019000954

    Article  CAS  PubMed  Google Scholar 

  11. Ma W, Bai W, Wu X, Zhao J, Li M, Zeng X (2020) Successful treatment of refractory thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus with combination of plasma exchange and low-dose rituximab. Lupus 29:1961–1967. https://doi.org/10.1177/0961203320953473

    Article  CAS  PubMed  Google Scholar 

  12. Scully M, Cataland SR, Peyvandi F, Coppo P, Knobl P, Kremer HJ, Metjian A, de la Rubia J, Pavenski K, Callewaert F, Biswas D, De Winter H, Zeldin RK (2019) Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med 380:335–346. https://doi.org/10.1056/NEJMoa1806311

    Article  CAS  PubMed  Google Scholar 

  13. Coppo P, Bubenheim M, Azoulay E, Galicier L, Malot S, Bige N, Poullin P, Provot F, Martis N, Presne C, Moranne O, Benainous R, Dossier A, Seguin A, Hie M, Wynckel A, Delmas Y, Augusto JF, Perez P, Rieu V, Barbet C, Lhote F, Ulrich M, Rumpler AC, de Witte S, Krummel T, Veyradier A, Benhamou Y (2021) A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP. Blood 137:733–742. https://doi.org/10.1182/blood.2020008021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mockel T, Basta F, Weinmann-Menke J, Schwarting A (2021) B cell activating factor (BAFF): structure, functions, autoimmunity and clinical implications in systemic lupus erythematosus (SLE). Autoimmun Rev 20:102736. https://doi.org/10.1016/j.autrev.2020.102736

    Article  CAS  PubMed  Google Scholar 

  15. Blair HA, Duggan ST (2018) Belimumab: a review in systemic lupus erythematosus. Drugs 78:355–366. https://doi.org/10.1007/s40265-018-0872-z

    Article  CAS  PubMed  Google Scholar 

  16. Kaul A, Gordon C, Crow MK, Touma Z, Urowitz MB, van Vollenhoven R, Ruiz-Irastorza G, Hughes G (2016) Systemic lupus erythematosus. Nat Rev Dis Primers 2:16039. https://doi.org/10.1038/nrdp.2016.39

    Article  PubMed  Google Scholar 

  17. Scully M, Cataland S, Coppo P, de la Rubia J, Friedman KD, Kremer HJ, Lammle B, Matsumoto M, Pavenski K, Sadler E, Sarode R, Wu H (2017) Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost 15:312–322. https://doi.org/10.1111/jth.13571

    Article  CAS  PubMed  Google Scholar 

  18. Lansigan F, Isufi I, Tagoe CE (2011) Microangiopathic haemolytic anaemia resembling thrombotic thrombocytopenic purpura in systemic lupus erythematosus: the role of ADAMTS13. Rheumatology (Oxford) 50:824–829. https://doi.org/10.1093/rheumatology/keq395

    Article  CAS  Google Scholar 

  19. George JN, Nester CM (2014) Syndromes of thrombotic microangiopathy. N Engl J Med 371:654–666. https://doi.org/10.1056/NEJMra1312353

    Article  CAS  PubMed  Google Scholar 

  20. Masias C, Cataland SR (2018) The role of ADAMTS13 testing in the diagnosis and management of thrombotic microangiopathies and thrombosis. Blood 132:903–910. https://doi.org/10.1182/blood-2018-02-791533

    Article  CAS  PubMed  Google Scholar 

  21. Sekine A, Hasegawa E, Hiramatsu R, Mise K, Sumida K, Ueno T, Yamanouchi M, Hayami N, Suwabe T, Hoshino J, Sawa N, Takaichi K, Ohashi K, Fujii T, Ubara Y (2015) Two types of renovascular lesions in lupus nephritis with clinical thrombotic thrombocytopenic purpura. Case Rep Nephrol Dial 5:192–199. https://doi.org/10.1159/000441107

    Article  PubMed  PubMed Central  Google Scholar 

  22. Niaz FA, Aleem A (2010) Response to rituximab in a refractory case of thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus. Saudi J Kidney Dis Transpl 21:109–112. http://sjkdt.org/text.asp?2010/21/1/109/58783

  23. Sakaguchi S, Mikami N, Wing JB, Tanaka A, Ichiyama K, Ohkura N (2020) Regulatory T cells and human disease. Annu Rev Immunol 38:541–566. https://doi.org/10.1146/annurev-immunol-042718-041717

    Article  CAS  PubMed  Google Scholar 

  24. Dominguez-Villar M, Hafler DA (2018) Regulatory T cells in autoimmune disease. Nat Immunol 19:665–673. https://doi.org/10.1038/s41590-018-0120-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Huang H, Sun W, Liang Y, Long XD, Peng Y, Liu Z, Wen X, Jia M (2014) CD(+)(4)CD(+)(25) Treg cells in thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus patients. Ren Fail 36:1263–1267. https://doi.org/10.3109/0886022X.2014.934649

    Article  CAS  PubMed  Google Scholar 

  26. Wu H, Birmingham DJ, Rovin B, Hackshaw KV, Haddad N, Haden D, Yu CY, Hebert LA (2008) D-dimer level and the risk for thrombosis in systemic lupus erythematosus. Clin J Am Soc Nephrol 3:1628–1636. https://doi.org/10.2215/CJN.01480308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Jiang H, An X, Li Y, Sun Y, Shen G, Tu Y, Tao J (2014) Clinical features and prognostic factors of thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus: a literature review of 105 cases from 1999 to 2011. Clin Rheumatol 33:419–427. https://doi.org/10.1007/s10067-013-2312-5

    Article  PubMed  Google Scholar 

  28. Roose E, Veyradier A, Vanhoorelbeke K (2020) Insights into ADAMTS13 structure: impact on thrombotic thrombocytopenic purpura diagnosis and management. Curr Opin Hematol 27:320–326. https://doi.org/10.1097/MOH.0000000000000602

    Article  CAS  PubMed  Google Scholar 

  29. Shenkman B, Einav Y (2014) Thrombotic thrombocytopenic purpura and other thrombotic microangiopathic hemolytic anemias: diagnosis and classification. Autoimmun Rev 13:584–586. https://doi.org/10.1016/j.autrev.2014.01.004

    Article  CAS  PubMed  Google Scholar 

  30. Graca N, Joly BS, Voorberg J, Vanhoorelbeke K, Beranger N, Veyradier A, Coppo P (2022) TTP: from empiricism for an enigmatic disease to targeted molecular therapies. Br J Haematol. https://doi.org/10.1111/bjh.18040

    Article  PubMed  Google Scholar 

  31. Ramskold D, Parodis I, Lakshmikanth T, Sippl N, Khademi M, Chen Y, Zickert A, Mikes J, Achour A, Amara K, Piehl F, Brodin P, Gunnarsson I, Malmstrom V (2019) B cell alterations during BAFF inhibition with belimumab in SLE. EBioMedicine 40:517–527. https://doi.org/10.1016/j.ebiom.2018.12.035

    Article  PubMed  Google Scholar 

  32. Singh JA, Shah NP, Mudano AS (2021) Belimumab for systemic lupus erythematosus. Cochrane Database Syst Rev 2:D10668. https://doi.org/10.1002/14651858.CD010668.pub2

    Article  Google Scholar 

  33. Stohl W, Hiepe F, Latinis KM, Thomas M, Scheinberg MA, Clarke A, Aranow C, Wellborne FR, Abud-Mendoza C, Hough DR, Pineda L, Migone TS, Zhong ZJ, Freimuth WW, Chatham WW (2012) Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum 64:2328–2337. https://doi.org/10.1002/art.34400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Becerra E, Scully MA, Leandro MJ, Heelas EO, Westwood JP, De La Torre I, Cambridge G (2015) Effect of rituximab on B cell phenotype and serum B cell-activating factor levels in patients with thrombotic thrombocytopenic purpura. CLIN EXP IMMUNOL 179:414–425. https://doi.org/10.1111/cei.12472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gerosa M, Gualtierotti R, Pisati M, Meroni PL (2016) Systemic lupus erythematosus complicated by thrombotic thrombocytopenic purpura. Clin Exp Rheumatol 34:S120–S121

    Google Scholar 

  36. Tong JJ, Xiao H, Xu SQ (2022) A case report of systemic lupus erythematosus presented as thrombotic thrombocytopenic purpura and successfully treated with plasmapheresis and belimumab. Ther Apher Dial. https://doi.org/10.1111/1744-9987.13807

    Article  PubMed  Google Scholar 

  37. Woods R, Farland A, Owen J (2019) Abstract Book of Joint 10th BIC and 3rd INHIBITORS in Hemophilia International Conference Genoa, Italy, September 6–8 2019. Haematologica 104:1–44. https://doi.org/10.3324/haematol.2019.s1

    Article  Google Scholar 

  38. Tulpule SA, Francis YA, Radia D, Harrison CN, Hunt BJ (2006) Safety and efficacy of mycophenolate mofetil in relapsing acquired thrombotic thrombocytopenic purpura: could it prevent further relapse? Blood 11(2006):3993. https://doi.org/10.1182/blood.V108.11.3993.3993

    Article  Google Scholar 

Download references

Acknowledgements

We acknowledge those who were involved in drafting and revising the manuscript. We would like to thank Editage (www.editage.cn) for the English language editing.

Funding

This study was supported by the Natural Science Foundation of Chongqing (cstc2018jcyjAX0260).

Author information

Author notes

  1. Shen-ju Liang and Quan-you Zheng contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology and Immunology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China

    Shen-ju Liang, Meng-Shan Li, Ming-Ye Lv, Wen-Ting Chen & Yi Yang

  2. Department of Nephrology and Urology, 958th Hospital, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400020, China

    Quan-you Zheng

Authors
  1. Shen-ju Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Quan-you Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Meng-Shan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ming-Ye Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wen-Ting Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Shen-ju Liang, Quan-you Zheng, and Yi Yang: case reporting, literature screening, manuscript preparation, and editing; Shen-ju Liang, Meng-shan Li, and Ming-ye Lv: patient follow-up and data acquisition; Wen-ting Chen and Yi Yang: conceptualization, review, support, and supervision. All the authors approved the final version of the manuscript.

Corresponding author

Correspondence to Yi Yang.

Ethics declarations

Disclosures

None.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liang, Sj., Zheng, Qy., Li, MS. et al. Response to belimumab in thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus: a case-based review. Clin Rheumatol 41, 2561–2569 (2022). https://doi.org/10.1007/s10067-022-06155-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-022-06155-6

Keywords

Search

Navigation