Abstract

Case Report

A Case of Catastrophic Atypical Hemolytic Uremic Syndrome Unresponsive to Eculizumab and the use of Ravulizumab Off-label

Jorge Cabrera Morales*, Giuseppe Sias, Marco Manzoni and Giacomina Loriga

Published: 05 October, 2023 | Volume 7 - Issue 3 | Pages: 073-077

“A 40-year-old woman with melanoma, under treatment with Dabrafenib and Trametinib, was evaluated in our hospital for rapidly progressive deterioration of renal function”. 
8 months before the current admission, the patient had been diagnosed with melanoma, and underwent radical surgery and subsequent therapy with Dabrafenib and Trametinib.
After 5 months of therapy, the patient was brought to this hospital for precordial pain, with a diagnosis of myopericarditis, therapy was started for heart failure with a good response. However, the patient developed a progressive impairment of renal function, associated with hemolytic anemia and thrombocytopenia. The peripheral smear showed the presence of schistocytes.
The suspicion of atypical Hemolytic Uremic Syndrome (aHUS) was confirmed by the assay of C5B-9 induced by serum on endothelial cells, which showed a deposition of 331%, treatment with Eculizumab was initiated.
After 3 administrations the patient did not improve, with further worsening of the hemolytic condition, and progression of renal damage.
Due to the failure of Eculizumab, we considered the use of Ravulizumab. However, in Italy only can be administered to patients in Eculizumab stable treatment for at least three months. Nevertheless, faced with the catastrophic condition, it was decided to shift the therapy and use off-label Ravulizumab. After 10 days of the first administration, the laboratory tests showed a continuous rise in the values of haptoglobin, platelets, and hemoglobin, and a decrease in LDH. The renal function failed to return to normal values but after 20 days of therapy with Ravulizumab, there was complete resolution of the hemolytic condition.

Read Full Article HTML DOI: 10.29328/journal.jcn.1001113 Cite this Article Read Full Article PDF

Keywords:

Atypical hemolytic uremic syndrome; Myopericarditis; Eculizumab; Ravulizumab; Plasma exchange; C5 blockade; End-stage chronic kidney disease

References

  1. Mazzierli T, Allegretta F, Maffini E, Allinovi M. Drug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management. Front Pharmacol. 2023 Jan 9;13:1088031. doi: 10.3389/fphar.2022.1088031. PMID: 36699080; PMCID: PMC9868185.
  2. Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011 Sep 8;6:60. doi: 10.1186/1750-1172-6-60. PMID: 21902819; PMCID: PMC3198674.
  3. Raina R, Krishnappa V, Blaha T, Kann T, Hein W, Burke L, Bagga A. Atypical Hemolytic-Uremic Syndrome: An Update on Pathophysiology, Diagnosis, and Treatment. Ther Apher Dial. 2019 Feb;23(1):4-21. doi: 10.1111/1744-9987.12763. Epub 2018 Oct 29. PMID: 30294946.
  4. Tschumi S, Gugger M, Bucher BS, Riedl M, Simonetti GD. Eculizumab in atypical hemolytic uremic syndrome: long-term clinical course and histological findings. Pediatr Nephrol. 2011 Nov;26(11):2085-8. doi: 10.1007/s00467-011-1989-4. Epub 2011 Aug 30. PMID: 21877169.
  5. Nishimura J, Yamamoto M, Hayashi S, Ohyashiki K, Ando K, Brodsky AL, Noji H, Kitamura K, Eto T, Takahashi T, Masuko M, Matsumoto T, Wano Y, Shichishima T, Shibayama H, Hase M, Li L, Johnson K, Lazarowski A, Tamburini P, Inazawa J, Kinoshita T, Kanakura Y. Genetic variants in C5 and poor response to eculizumab. N Engl J Med. 2014 Feb 13;370(7):632-9. doi: 10.1056/NEJMoa1311084. PMID: 24521109.
  6. McKeage K. Ravulizumab: First Global Approval. Drugs. 2019 Feb;79(3):347-352. doi: 10.1007/s40265-019-01068-2. PMID: 30767127.
  7. Connelly-Smith L, Alquist CR, Aqui NA, Hofmann JC, Klingel R, Onwuemene OA, Patriquin CJ, Pham HP, Sanchez AP, Schneiderman J, Witt V, Zantek ND, Dunbar NM. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Ninth Special Issue. J Clin Apher. 2023 Apr;38(2):77-278. doi: 10.1002/jca.22043. PMID: 37017433.
  8. Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, Pessoa V, Gualandro S, Füreder W, Ptushkin V, Rottinghaus ST, Volles L, Shafner L, Aguzzi R, Pradhan R, Schrezenmeier H, Hill A. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019 Feb 7;133(6):530-539. doi: 10.1182/blood-2018-09-876136. Epub 2018 Dec 3. PMID: 30510080; PMCID: PMC6367644.
  9. Banks M, Crowell K, Proctor A, Jensen BC. Cardiovascular Effects of the MEK Inhibitor, Trametinib: A Case Report, Literature Review, and Consideration of Mechanism. Cardiovasc Toxicol. 2017 Oct;17(4):487-493. doi: 10.1007/s12012-017-9425-z. PMID: 28861837; PMCID: PMC6319910.
  10. Banks M, Crowell K, Proctor A, Jensen BC. Cardiovascular Effects of the MEK Inhibitor, Trametinib: A Case Report, Literature Review, and Consideration of Mechanism. Cardiovasc Toxicol. 2017 Oct;17(4):487-493. doi: 10.1007/s12012-017-9425-z. PMID: 28861837; PMCID: PMC6319910.
  11. Lyon AR, López-Fernández T, Couch LS, Asteggiano R, Aznar MC, Bergler-Klein J, Boriani G, Cardinale D, Cordoba R, Cosyns B, et al. ESC Scientific Document Group. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022 Nov 1;43(41):4229-4361. doi: 10.1093/eurheartj/ehac244. Erratum in: Eur Heart J. 2023 May 7;44(18):1621. PMID: 36017568.
  12. Reese JA, Bougie DW, Curtis BR, Terrell DR, Vesely SK, Aster RH, George JN. Drug-induced thrombotic microangiopathy: Experience of the Oklahoma Registry and the BloodCenter of Wisconsin. Am J Hematol. 2015 May;90(5):406-10. doi: 10.1002/ajh.23960. Epub 2015 Feb 25. PMID: 25639727; PMCID: PMC4409501.
  13. Akino S, Ohashi H, Okano T, Takeuchi S, Kawakami T, Soma Y, Kadono T. Sudden elevation of plasma D-dimer levels induced by the combination therapy of dabrafenib and trametinib: Report of two cases. J Dermatol. 2019 Apr;46(4):358-360. doi: 10.1111/1346-8138.14798. Epub 2019 Feb 5. PMID: 30719722.
  14. Zafar A, Lim MY, Abou-Ismail MY. Eculizumab in the management of drug-induced thrombotic microangiopathy: A scoping review of the literature. Thromb Res. 2023 Apr;224:73-79. doi: 10.1016/j.thromres.2023.02.012. Epub 2023 Mar 2. PMID: 36871347.
  15. Rondeau E, Scully M, Ariceta G, Barbour T, Cataland S, Heyne N, Miyakawa Y, Ortiz S, Swenson E, Vallee M, Yoon SS, Kavanagh D, Haller H; 311 Study Group. The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment. Kidney Int. 2020 Jun;97(6):1287-1296. doi: 10.1016/j.kint.2020.01.035. Epub 2020 Mar 6. Erratum in: Kidney Int. 2020 Dec;98(6):1621. Erratum in: Kidney Int. 2021 May;99(5):1244. PMID: 32299680.
  16. Peffault de Latour R, Brodsky RA, Ortiz S, Risitano AM, Jang JH, Hillmen P, Kulagin AD, Kulasekararaj AG, Rottinghaus ST, Aguzzi R, Gao X, Wells RA, Szer J. Pharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised, multicentre studies. Br J Haematol. 2020 Nov;191(3):476-485. doi: 10.1111/bjh.16711. Epub 2020 May 24. PMID: 32449174; PMCID: PMC7687070.
  17. Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, Smolen JS, Wofsy D, Boumpas DT, Kamen DL, Jayne D, Cervera R, Costedoat-Chalumeau N, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019 Sep;71(9):1400-1412. doi: 10.1002/art.40930. Epub 2019 Aug 6. PMID: 31385462; PMCID: PMC6827566.

Figures:

Figure 1

Figure 1

Similar Articles

Recently Viewed

  • Characteristics of Juvenile Sex Offenders in Poland
    Anna Więcek-Durańska* Anna Więcek-Durańska*. Characteristics of Juvenile Sex Offenders in Poland. J Forensic Sci Res. 2023: doi: 10.29328/journal.jfsr.1001053; 7: 072-076
  • Hypercalcaemic Crisis Associated with Hyperthyroidism: A Rare and Challenging Presentation
    Karthik Baburaj*, Priya Thottiyil Nair, Abeed Hussain and Vimal MV Karthik Baburaj*, Priya Thottiyil Nair, Abeed Hussain, Vimal MV. Hypercalcaemic Crisis Associated with Hyperthyroidism: A Rare and Challenging Presentation. Ann Clin Endocrinol Metabol. 2024: doi: 10.29328/journal.acem.1001029; 8: 001-003
  • Physicians’ Anxiety Post-COVID Pandemic: A Cross-Sectional Study
    Ismail Hanine*, Mouna Chtibi, Kenza Hajjami, Siham Belbachir, Mohamed Kadiri and Abderrazzak Ouanass Ismail Hanine*, Mouna Chtibi, Kenza Hajjami, Siham Belbachir, Mohamed Kadiri, Abderrazzak Ouanass. Physicians’ Anxiety Post-COVID Pandemic: A Cross-Sectional Study. Arch Psychiatr Ment Health. 2024: doi: 10.29328/journal.apmh.1001054; 8: 032-037
  • Current anesthesıa for Cesarean Sectıon
    Demet Dogan Erol* and Ismail Aytac Demet Dogan Erol*, Ismail Aytac. Current anesthesıa for Cesarean Sectıon. Clin J Obstet Gynecol. 2018: doi: 10.29328/journal.cjog.1001011; 1: 061-066
  • Therapy of Walker Carcinosarcoma with Pectin and Cyclophosphane
    NY Alimzhanov, ISh Chakeev, BN Lepshin, IO Kudaibergenova, BA Shaimurzayeva, LV Serikova and Sh Jorobekova* NY Alimzhanov, ISh Chakeev, BN Lepshin, IO Kudaibergenova, BA Shaimurzayeva, LV Serikova, Sh Jorobekova*. Therapy of Walker Carcinosarcoma with Pectin and Cyclophosphane. J Radiol Oncol. 2023: doi: 10.29328/journal.jro.1001056; 7: 066-070

Read More

Most Viewed

Read More

Help ?