Complement Regulatory Genetic Mutations in the Setting of Autoimmune Thrombotic Thrombocytopenic Purpura: A Case Series

Mayo Clinic Proceedings. Innovations, Quality & Outcomes
Shebli AtrashPooja Motwani

Abstract

To explore the benefits of adding eculizumab for the treatment of refractory autoimmune thrombotic thrombocytopenic purpura (iTTP) with complement dysregulation. From January 1, 2014, through July 1, 2017, we identified patients with iTTP defined by ADAMTS13 (disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) levels less than 5% and the presence of ADAMTS13 inhibitor. Patients who progressed after receiving standard of care management for iTTP were subjected to a comprehensive evaluation to look for evidence of complement activation. Herein, we share our single-institute experience regarding the clinical course and treatment algorithm for 3 patients with refractory iTTP. All the patients had clinical deterioration despite treatment with plasma exchange, corticosteroids, rituximab, and vincristine, which prompted us to look for evidence of complement activation and associated genetic mutations. Complement-related genetic aberrations were present in all 3 patients, who had had different degrees of complement activation. The first 2 patients did not benefit from eculizumab when treatment was started before complete clearance of inhibitors to ADAMTS13. However, they had durable remissions when eculizum...Continue Reading

References

Dec 14, 2004·Journal of the American Society of Nephrology : JASN·Marie-Agnès Dragon-DureyVéronique Frémeaux-Bacchi
Mar 14, 2012·British Journal of Haematology·John ChapinJeffrey Laurence
Sep 19, 2012·Nature Reviews. Nephrology·Marina NorisGiuseppe Remuzzi
Oct 29, 2013·Seminars in Nephrology·Marina Noris, Giuseppe Remuzzi
Apr 22, 2015·The American Journal of Dermatopathology·Cynthia M MagroJeffrey C Laurence

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Citations

Mar 14, 2019·Current Opinion in Nephrology and Hypertension·Ramy M HannaRichard Burwick
Jul 17, 2021·Medicina clínica·María Eva Mingot CastellanoUNKNOWN Grupo Español de Aféresis (GEA)

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