Atypical hemolytic-uremic syndrome: etiopathogenesis, diagnosis and therapy

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Abstract

Atypical hemolytic-uremic syndrome (aHUS) is one of the variants of primary thrombotic microangiopathies (TMA). It is based on chronic uncontrolled activation of the complement system due to mutations in the genes of regulatory proteins of the alternative pathway of the complement system of hereditary or acquired nature. The result of this is endothelial damage leading to generalized thrombus formation in the microvasculature (so-called complement-mediated TMA). The main manifestations are thrombocytopenia, microangiopathic hemolytic anemia and organ damage, making up the classic triad of TMA. The diagnosis of aHUS is a diagnosis of exclusion. It is established on the basis of the characteristic clinical picture after excluding all other forms of TMA, both primary and secondary. The treatment of aHUS is based on the use of plasma exchange and anti-C5 monoclonal antibodies.

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About the authors

E. B. Zukhovitskaya

Grodno State Medical University

Author for correspondence.
Email: gematolog.lz@gmail.com

Candidate of Medical Sciences

Belarus, Grodno

E. N. Kabaeva

Belarusian State Medical University

Email: gematolog.lz@gmail.com

Candidate of Medical Sciences

Belarus, Minsk

D. G. Tsvirko

Belarusian State Medical University

Email: gematolog.lz@gmail.com

Candidate of Medical Sciences

Belarus, Minsk

References

  1. Yoshida Y., Kato H., Ikeda Y. еt al. Pathogenesis of atypical haemolytic uraemic syndrome. J Atheroscler Thromb. 2019; 26 (2): 99–110. doi: 10.5551/jat.RV17026
  2. Cordoba R., Hidalgo M.S., Pinto еt S. al. Genetics of atypical hemolytic uremic syndrome (aHUS). Semin Thromb Hemost. 2014; 40 (4): 422–30. doi: 10.1055/s-0034-1375296
  3. Fakhouri F., Zuber J., Frémeaux-Bacchi V. еt al. Hemolytic uremic syndrome. Lancet. 2017; 390 (10095): 681–96. doi: 10.1016/S0140-6736(17)30062-4
  4. Yan К., Desai K., Gullapalli L. еt al. Epidemiology of atypical hemolytic uremic syndrome: a systematic literature review. Clin Epidemiol. 2020; 12: 295–305. doi: 10.2147/CLEP.S245642
  5. Shen Y.M. Clinical evaluation of thrombotic microangiopathy: identification of patients with suspected atypical hemolytic uremic syndrome. Thromb J. 2016; 14 (Suppl 1): 19. doi: 10.1186/s12959-016-0114-0
  6. Go R.S., Winters J.L., Leung N. еt al. Thrombotic microangiopathy care pathway: a consensus statement for the Mayo Clinic complement alternative pathway – thrombotic microangiopathy (CAP-TMA) disease-oriented group. Mayo Clin Proc. 2016; 91 (9): 1189–211. doi: 10.1016/j.mayocp.2016.05.015
  7. Gupta M., Govindappagari S., Burwick R.M. Pregnancy-associated atypical hemolytic uremic syndrome. A systematic review. Obstet Gynecol. 2020; 135 (1): 46–58. doi: 10.1097/AOG0000000000003554
  8. Praga M., de Cordoba S.R. Secondary atypical hemolytic uremic syndrome in the era of complement blockade. Kidney Int. 2019; 95 (6): 1298–300. doi: 10.1016/j/kint2019.01.043
  9. Cataland S.R., Wu H.M. Atypical haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura: clinically differentiating the thrombotic microangiopathies. Eur J Intern Med. 2017; 24 (6): 486–91. doi: 10.1016/j.ejim.2013.05.007
  10. Loirat С., Garnier A., Sellier-Leclerc A.-L. et al. Plasmatherapy in atypical hemolytic uremic syndrome. Semin Thromb Hemost. 2016; 36 (6): 673–81. doi: 10.1055/s-0030-1262890
  11. Козловская Н.Л., Коротчаева Ю.В., Шифман Е.М. и др. Акушерский атипичный гемолитико-уремический синдром: виновата беременность или ее осложнения? Вопросы гинекологии, акушерства и перинатологии. 2020; 19 (4): 81–91 [Kozlovskaya N.L., Korotchaeva Yu.V., Shifman Ye.M. et al. Pregnancy-associated atypical hemolytic-uremic syndrome: is pregnancy to blame or its complications? Gynecology, Obstetrics and Perinatology. 2020; 19 (4): 81–91 (in Russ.)]. doi: 10.20953/1726–1678-2020-4-81-91
  12. Wada Н., Matsumoto T., Suzuki K. еt al. Differences and similarities between disseminated intravascular coagulation and thrombotic microangiopathy. Thromb J. 2018; 16: 14. doi: 10.1186/s12959-018-0168-2
  13. Schwartz J., Padmanabhan A., Aqui N. еt al. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: the seventh special issue. J Clin Apher. 2016; 31 (3): 149–62. doi: 10.1002/jca.21470
  14. Menne J., Delmas Y., Fakhouri F. еt al. Outcome in patients with atypical hemolytic uremic syndrome treated with Eculizumab in a long-term observational study. BMC Nephrol. 2019; 20 (1): 125–37. doi: 10.1186/s12882-019-1314-1
  15. Menne J., Delmas Y., Fakhouri F. еt al. Eculizumab prevents thrombotic microangiopathy in patients with atypical hemolytic uremic syndrome in a long-term observational study. Clin Kidney J. 2018; 12 (2): 196–205. doi: 10.1093/ckj/sfy035
  16. Olson S.R., Lu E., Sulpizio E. еt al. When to stop Eculizumab in complement-mediated microangiopathies. Am J Nephrol. 2018; 48 (2): 96–107. doi: 10.1159/000492033
  17. Птушкин В.В., Кулагин А.Д., Лукина Е.А. и др. Результаты открытого многоцентрового клинического исследования Ib фазы по оценке безопасности, фармакокинетики и фармакодинамики первого биоаналога экулизумаба у нелеченых пациентов с пароксизмальной ночной гемоглобинурией в фазе индукции терапии. Терапевтический архив. 2020; 92 (7): 77–84 [Ptushkin V.V., Kulagin A.D., Lukina E.A. et al. Results of phase Ib open multicenter clinical trial of the safety, pharmacokinetics and pharmacodynamics of first biosimilar of eculizumab in untreated patients with paroxysmal nocturnal hemoglobinuria during induction of therapy. Terapevticheskii arkhiv. 2020; 92 (7): 77–84 (in Russ.)]. doi: 10.26442/00403660.2020.07.000818
  18. Kulagin A., Ptushkin V., Lukina E. et al. Randomized multicenter noninferiority phase III clinical trial of the first biosimilar of eculizumab. Ann Hematol. 2021; 100 (11): 2689–98. doi: 10.1007/s00277-021-04624-7
  19. Коротчаева Ю.В., Козловская Н.Л., Шифман Е.М. Сравнительный анализ эффективности препаратов экулизумаба в лечении акушерского атипичного гемолитико-уремического синдрома. Клиническая фармакология и терапия. 2021; 30 (3): 25–30 [Korotchaeva Y.V., Kozlovskaya N.L., Shifman E.M. Comparative efficacy of the original and biosimilar eculizumab in the treatment of obstetric atypical hemolytic-uremic syndrome. Clin Pharmacol Ther. 2021; 30 (3): 25–30 (in Russ.)]. doi: 10.32756/0869-5490-2021-3-25-30
  20. Lavrishcheva I.V., Jakovenko A.A., Kudlay D.A. A case report of atypical hemolytic-uremic syndrome treatment with the first Russian eculizumab in adult patient. Urology & Nephrology Open Access Journal. 2020; 8 (2): 37–40. doi: 10.15406/unoaj.2020.08.00272
  21. Лаврищева Ю.В., Яковенко А.А., Кудлай Д.А. Опыт применения российского биоаналога оригинального препарата экулизумаба для лечения больных атипичным гемолитико-уремическим синдромом. Терапевтический архив. 2020; 92 (6): 76–80 [Lavrishcheva Y.V., Yakovenko A.A., Kudlai D.A. The experience of using the Russian biosimilar of the original drug eculizumab for the treatment of patients with atypical hemolytic-uremic syndrome. Terapevticheskii arkhiv. 2020; 92 (6): 76–80 (in Russ.)]. doi: 10.26442/00403660.2020.06.000649
  22. Эмирова Х.М., Орлова О.М., Музуров А.Л. и др. Опыт применения Элизарии® при атипичном гемолитико-уремическом синдроме. Педиатрия. Журнал им. Г.Н. Сперанского. 2019; 98 (5): 225–9 [Emirova Kh.М., Orlova O.M., Мuzurov А.L. et al. The experience of using Elizaria® for atypical hemolytic uremic syndrome. Pediatria n.a. G.N. Speransky. 2019; 98 (5): 225–9 (in Russ.)]. doi: 10.24110/0031-403X-2019-98-5-225-229
  23. Козловская Н.Л., Добронравов В.А., Боброва Л.А. и др. Клинические рекомендации по ведению взрослых пациентов с атипичным гемолитико-уремическим синдромом. Нефрология и диализ. 2023; 25 (4): 465–92 [Kozlovskaya N.L., Dobronravov V.A., Bobrova L.A. et al. Clinical guidelines for the management of adult patients with atypical hemolytic-uremic syndrome. Nephrology and Dialysis. 2023; 25 (4): 465–92 (in Russ.)]. doi: 10.28996/2618-9801-2023-4-465-492
  24. Gonzalez Suarez M.L., Thongprayoon C., Mao M.A. et al. Outcomes of Kidney Transplant Patients with Atypical Hemolytic Uremic Syndrome Treated with Eculizumab: A Systematic Review and Meta-Analysis. J Clin Med. 2019; 8 (7): E919. doi: 10.3390/jcm8070919

Supplementary files

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1. JATS XML
2. Algorithm of differential diagnosis of thrombotic microangiopathies.

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