Aplasia medular devido ao uso de azatioprina em paciente com hepatite autoimune. Apresentação de um caso
DOI:
https://doi.org/10.5281/zenodo.13736220Palavras-chave:
azatioprina, imunossupressor, aplasia medular, hepatite, pancitopeniaResumo
A azatioprina é um medicamento imunossupressor derivado da 6-mercaptopurina, utilizado no tratamento de diversas doenças autoimunes. Seu metabolismo envolve principalmente xantina oxidase e tiopurina metiltransferase (TPMT). Os efeitos adversos da azatioprina incluem reações alérgicas e mielotoxicidade, como leucopenia, trombocitopenia e anemia, cuja incidência pode chegar a 46% em pacientes com hepatite autoimune. O caso apresentado descreve uma mulher de 68 anos com hepatite autoimune tratada inicialmente com prednisona e continuada com azatioprina. Posteriormente, ele desenvolveu queda de cabelo, astenia e perda de peso, juntamente com pancitopenia confirmada em laboratório. Após o diagnóstico de aplasia medular secundária à toxicidade da azatioprina, a medicação foi suspensa e iniciado tratamento com antibióticos, transfusões e corticosteróides, obtendo-se recuperação hematológica completa e evolução favorável.
Downloads
Não há dados estatísticos.
Referências
1. Mazzaroni S, Forero O, Candiz ME, Pérez D, Olivares L. La importancia de la solicitud de tiopurina metiltransferasa para el inicio de la azatioprina. Nuestra experiencia. Dermatol Argent [Internet] 2018 [citado 18 Jul 2024]; 24(4):199–201. Disponible en: https://www.dermatolarg.org.ar/index.php/dermatolarg/article/view/1800
2. Prieto Ortiz J, Preciado J, Huertas Pacheco S. Hepatitis autoinmune. Rev Col Gastroenterol [Internet] 2012 [citado 17 Jul 2024]; 27(4):303-315. Disponible en: http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0120-99572012000400007&lng=en
3. Gómez Piña J, Trujillo Alonso J, Morales Hernández A. Azathioprine-induced myelosuppression in Sjogren’s syndrome. Hematol Méx [Internet] 2022 [citado 17 Jul 2024]; 23(2):107-110. Disponible en: https://www.medigraphic.com/pdfs/hematologia/re-2022/re222d.pdf
4. Correa A, Henriques L, Mourao C, Fonseca J, Leandro J. Simultaneous monitoring of azathioprine metabolites in erythrocytes of Crohn’s disease patients by HPLC-UV. J Chromatogr Sci [Internet] 2022 [citado 17 Jul 2024]; 60(6):518–24. DOI: http://dx.doi.org/10.1093/chromsci/bmab084
5. Kennedy NA, Rhatigan E, Arnott IDR, Noble CL, Shand AG, Satsangi J, et al. A trial of mercaptopurine is a safe strategy in patients with inflammatory bowel disease intolerant to azathioprine: an observational study, systematic review and meta‐analysis. Aliment Pharmacol Ther [Internet] 2013 [citado 17 Jul 2024]; 38(10):1255–66. DOI: http://dx.doi.org/10.1111/apt.12511
6. Buhl M, Gómez G, Collado M, Oddo E, Khoury M, Azurmendi P, et al. Variantes genéticas de la tiopurina metiltransferasa e incidencia de eventos adversos en pacientes con indicación de azatioprina. Medicina (B. Aires) [Internet] 2018 [citado 17 Jul 2024]; 78(2):65-70. Disponible en: http://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S0025-76802018000200001&lng=es
7. Iamonico E, Camps F, Populin M, Vega A, Meccico M, Gutiérrez M, et al. Hepatitis asociada a aplasia medular. RAM [Internet] 2017 [citado 18 Jul 2024]; 5(1):55-66. Disponible en: https://www.semanticscholar.org/paper/HEPATITIS-ASOCIADA-A-APLASIA-MEDULAR-Iamonico-Camps/1258191db2f193965e74e6c32e207a5897e762a4
8. Díaz Ramírez GS, Jimenez Rivera DF, Escobar DM, Vargas Potes CJ, Rojas Rodríguez CA, Rojas Rojas NE. Caracterización de pacientes con diagnóstico de hepatitis autoinmune en un hospital de cuarto nivel de Cali, 2014-2020. Rev Colomb Gastroenterol [Internet] 2023 [citado 17 Jul 2024]; 38(1):2-11. DOI: https://doi.org/10.22516/25007440.907
9. Biswajit H, Pratim PP, Kumar ST, Shilpi S, Krishna GB, Aditi A. Aplastic anemia: a common hematological abnormality among peripheral pancytopenia. N Am J Med Sci [Internet] 2012 [citado 17 Jul 2024]; 4(9):384-8. DOI: https://doi.org/10.4103/1947-2714.100980
10. Pruijt J, Haanen J, Hollander A, Ottolander G. Azathioprine-induced pure red-cell aplasia. Nephrology Dialysis Transplantation [Internet] 1996 [citado 17 Jul 2024]; 11:1371-1373. Disponible en: https://pubmed.ncbi.nlm.nih.gov/8672045/
11. Connell WR, Kamm MA, Ritchie JK, Lennard-Jones JE. Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience. Gut [Internet] 1993 [citado 18 Jul 2024]; 34(8):1081–5. DOI: https://doi.org/10.1136/gut.34.8.1081
12. Present DH, Meltzer S, Krumholz M, Wolke A, Korelitz B. 6-mercaptopurine in the management of inflammatory bowel disease: Short- and long-term toxicity. Ann Intern Med [Internet] 1989 [citado 17 Jul 2024]; 111(8):641-649. DOI: http://dx.doi.org/10.7326/0003-4819-111-8-641
13. Martínez C, Ros I, Martínez J, Sorribes J, López M, Rodríguez C. Pancitopenia inducida por azatioprina. Arch Argent Pediatr [Internet] 2016 [citado 17 Jul 2024]; 114(4):e252-e255. DOI: http://dx.doi.org/10.5546/aap.2016.e252
14. Kim HS, Park BK, Kim SK, Han SB, Lee JW, Lee D-G, et al. Clinical characteristics and outcomes of Pseudomonas aeruginosa bacteremia in febrile neutropenic children and adolescents with the impact of antibiotic resistance: a retrospective study. BMC Infect Dis [Internet] 2017 [citado 17 Jul 2024]; 17(1). DOI: http://dx.doi.org/10.1186/s12879-017-2597-0
15. Hoffman R, Benz E, Silberstein L, Heslop H, Weitz J, Salama M, et al. Hematology Basic Principles and Practice. 8va ed. USA: Elsevier; 2023. p. 397.
2. Prieto Ortiz J, Preciado J, Huertas Pacheco S. Hepatitis autoinmune. Rev Col Gastroenterol [Internet] 2012 [citado 17 Jul 2024]; 27(4):303-315. Disponible en: http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0120-99572012000400007&lng=en
3. Gómez Piña J, Trujillo Alonso J, Morales Hernández A. Azathioprine-induced myelosuppression in Sjogren’s syndrome. Hematol Méx [Internet] 2022 [citado 17 Jul 2024]; 23(2):107-110. Disponible en: https://www.medigraphic.com/pdfs/hematologia/re-2022/re222d.pdf
4. Correa A, Henriques L, Mourao C, Fonseca J, Leandro J. Simultaneous monitoring of azathioprine metabolites in erythrocytes of Crohn’s disease patients by HPLC-UV. J Chromatogr Sci [Internet] 2022 [citado 17 Jul 2024]; 60(6):518–24. DOI: http://dx.doi.org/10.1093/chromsci/bmab084
5. Kennedy NA, Rhatigan E, Arnott IDR, Noble CL, Shand AG, Satsangi J, et al. A trial of mercaptopurine is a safe strategy in patients with inflammatory bowel disease intolerant to azathioprine: an observational study, systematic review and meta‐analysis. Aliment Pharmacol Ther [Internet] 2013 [citado 17 Jul 2024]; 38(10):1255–66. DOI: http://dx.doi.org/10.1111/apt.12511
6. Buhl M, Gómez G, Collado M, Oddo E, Khoury M, Azurmendi P, et al. Variantes genéticas de la tiopurina metiltransferasa e incidencia de eventos adversos en pacientes con indicación de azatioprina. Medicina (B. Aires) [Internet] 2018 [citado 17 Jul 2024]; 78(2):65-70. Disponible en: http://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S0025-76802018000200001&lng=es
7. Iamonico E, Camps F, Populin M, Vega A, Meccico M, Gutiérrez M, et al. Hepatitis asociada a aplasia medular. RAM [Internet] 2017 [citado 18 Jul 2024]; 5(1):55-66. Disponible en: https://www.semanticscholar.org/paper/HEPATITIS-ASOCIADA-A-APLASIA-MEDULAR-Iamonico-Camps/1258191db2f193965e74e6c32e207a5897e762a4
8. Díaz Ramírez GS, Jimenez Rivera DF, Escobar DM, Vargas Potes CJ, Rojas Rodríguez CA, Rojas Rojas NE. Caracterización de pacientes con diagnóstico de hepatitis autoinmune en un hospital de cuarto nivel de Cali, 2014-2020. Rev Colomb Gastroenterol [Internet] 2023 [citado 17 Jul 2024]; 38(1):2-11. DOI: https://doi.org/10.22516/25007440.907
9. Biswajit H, Pratim PP, Kumar ST, Shilpi S, Krishna GB, Aditi A. Aplastic anemia: a common hematological abnormality among peripheral pancytopenia. N Am J Med Sci [Internet] 2012 [citado 17 Jul 2024]; 4(9):384-8. DOI: https://doi.org/10.4103/1947-2714.100980
10. Pruijt J, Haanen J, Hollander A, Ottolander G. Azathioprine-induced pure red-cell aplasia. Nephrology Dialysis Transplantation [Internet] 1996 [citado 17 Jul 2024]; 11:1371-1373. Disponible en: https://pubmed.ncbi.nlm.nih.gov/8672045/
11. Connell WR, Kamm MA, Ritchie JK, Lennard-Jones JE. Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience. Gut [Internet] 1993 [citado 18 Jul 2024]; 34(8):1081–5. DOI: https://doi.org/10.1136/gut.34.8.1081
12. Present DH, Meltzer S, Krumholz M, Wolke A, Korelitz B. 6-mercaptopurine in the management of inflammatory bowel disease: Short- and long-term toxicity. Ann Intern Med [Internet] 1989 [citado 17 Jul 2024]; 111(8):641-649. DOI: http://dx.doi.org/10.7326/0003-4819-111-8-641
13. Martínez C, Ros I, Martínez J, Sorribes J, López M, Rodríguez C. Pancitopenia inducida por azatioprina. Arch Argent Pediatr [Internet] 2016 [citado 17 Jul 2024]; 114(4):e252-e255. DOI: http://dx.doi.org/10.5546/aap.2016.e252
14. Kim HS, Park BK, Kim SK, Han SB, Lee JW, Lee D-G, et al. Clinical characteristics and outcomes of Pseudomonas aeruginosa bacteremia in febrile neutropenic children and adolescents with the impact of antibiotic resistance: a retrospective study. BMC Infect Dis [Internet] 2017 [citado 17 Jul 2024]; 17(1). DOI: http://dx.doi.org/10.1186/s12879-017-2597-0
15. Hoffman R, Benz E, Silberstein L, Heslop H, Weitz J, Salama M, et al. Hematology Basic Principles and Practice. 8va ed. USA: Elsevier; 2023. p. 397.
Publicado
2025-02-17
Como Citar
1.
Loaiza Vega RA, Benitez Guzman KM. Aplasia medular devido ao uso de azatioprina em paciente com hepatite autoimune. Apresentação de um caso. Rev Inf Cient [Internet]. 17º de fevereiro de 2025 [citado 3º de abril de 2025];104:e4769. Disponível em: https://revinfcientifica.sld.cu/index.php/ric/article/view/4769
Edição
Seção
Relatos de Casos
