The burden of iron overload in sickle cell disease: insights from South Carolina, USA.
La sobrecarga de hierro en la anemia falciforme: perspectivas desde Carolina del Sur, EEUU.
Palabras clave:
Anemia de Células Falciformes, Sobrecarga de Hierro, Concentración Hepática de Hierro, Ferritina, Pruebas de Función Hepática, Terapia por Quelación
Resumen
Las transfusiones de glóbulos rojos pueden provocar sobrecarga de hierro (SH) en la enfermedad de células falciformes (ECF). Nuestro objetivo fue determinar la relación entre pacientes con ECF con SH y comorbilidades asociadas a la ECF. También se estudió el régimen de quelación de hierro para la SH en pacientes con ECF. Se estudió una cohorte de 245 pacientes adultos con ECF atendidos en la Medical University of South Carolina (MUSC). La información se obtuvo de las historias clínicas. Se realizó un análisis estadístico para analizar las correlaciones y las razones de probabilidades (odds ratios) con intervalos de confianza del 95%. Se encontraron 85 (34,7%) participantes con criterios de SH. Los resultados mostraron una asociación significativa de la SH con el ictus (OR = 14,67, p = 0,0001), la hipertensión pulmonar (OR = 4,75, p = 0,0006), el síndrome torácico agudo (OR = 2,46, p = 0,003) y la trombosis venosa profunda (OR = 1,84, p = 0,04). Se observó una fuerte correlación entre la concentración hepática de hierro (CHH) y el nivel de ferritina (r = 0,5148, p<0,0001). Las enzimas hepáticas se correlacionaron adecuadamente con la CHH y los niveles de ferritina. El 86% de los participantes (74/85) recibía terapia de quelación, pero solo el 19% obtuvo una buena respuesta al tratamiento. Un tercio de los pacientes con enfermedad de células falciformes desarrolló sobrecarga de hierro asociada a diversas comorbilidades. Las medidas integrales deben incluir determinaciones periódicas de la CHH y la ferritina, seguidas de un tratamiento de quelación adecuado para prevenir el daño orgánico.
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Chou ST, Alsawas M, Fasano RM, Field JJ, Hendrickson JE, Howard J, et al. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv. 2020; 28;4(2):327-355. https://doi.org/10.1182/bloodadvances.2019001143.
Harmatz P, Butensky E, Quirolo K, Williams R, Ferrell L, Moyer T, et al. Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy. Blood. 2000;96(1):76- 79. https://doi.org/10.1182/blood.V96.1.76.
Theocharidou E, Suddle AR. The Liver in Sickle Cell Disease. Clin Liver Dis. 2019;23(2):177-189. https://doi.org/10.1016/j.cld.2018.12.002.
Coates TD, Wood JC. How we manage iron overload in sickle cell patients. Br J Haematol. 2017;177(5):703-716. https://doi.org/10.1111/bjh.14575.
Badawy SM, Liem RI, Rigsby CK, Labotka RJ, DeFreitas RA, Thompson AA. Assessing cardiac and liver iron overload in chronically transfused patients with sickle cell disease. Br J Haematol. 2016;175(4):705- 713. https://doi.org/10.1111/bjh.14277.
Porter J, Garbowski M. Consequences and management of iron overload in sickle cell disease. Hematology Am Soc Hematol Educ Program. 2013;2013(1):447-456. https://doi.org/10.1182/asheducation-2013.1.447.
Noetzli LJ, Coates TD, Wood JC. Pancreatic iron loading in chronically transfused sickle cell disease is lower than in thalassaemia major. Br J Haematol. 2011;152(2):229-233. https://doi.org/10.1111/j.1365-2141.2010.08476.x.
Marsella M, Borgna-Pignatti C. Transfusional iron overload and iron chelation therapy in thalassemia major and sickle cell disease. Hematol Oncol Clin North Am 2014;28(4):703-727, vi. https://doi.org/10.1016/j.hoc.2014.04.004.
Fung EB, Harmatz P, Milet M, Ballas SK, De Castro L, Hagar W, et al; MultiCenter Study of Iron Overload Research Group. Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: A report from the multi-center study of iron overload. Am J Hematol. 2007;82(4):255-265. https://doi.org/10.1002/ajh.20809.
Ballas SK. Iron overload is a determinant of morbidity and mortality in adult patients with sickle cell disease. Semin Hematol. 2001;38 (1 Suppl 1):30-36. https://doi.org/10.1016/S0037-1963(01)90058-7.
Njoku F, Pugh N, Brambilla D, Kroner B, Shah N, Treadwell M, et al. Mortality in adults with sickle cell disease: Results from the sickle cell disease implementation consortium (SCDIC) registry. Am J Hematol. 2024;99(5):900-909. https://doi.org/10.1002/ajh.27279.
Piel FB, Jobanputra M, Gallagher M, Weber J, Laird SG, McGahan M. Co-morbidities and mortality in patients with sickle cell disease in England: A 10-year cohort analysis using hospital episodes statistics (HES) data. Blood Cells Mol Dis. 2021; 89:102567. https://doi.org/10.1016/j.bcmd.2021.102567.
Webb J, Kwiatkowski JL. Stroke in patients with sickle cell disease. Expert Rev Hematol. 2013;6(3):301-316. https://doi.org/10.1586/ehm.13.25.
van Tuijn CFJ, Schimmel M, Van Beers EJ, Nur E, Biemond BJ. Prospective evaluation of chronic organ damage in adult sickle cell patients: A seven‐year follow‐up study. Am J Hematol. 2017;92(10):E584-E590. https://doi.org/10.1002/ajh.24855.
Fortuna V, Lima J, Oliveira GF, Oliveira YS, Getachew B, Nekhai S, et al. Ferroptosis as an emerging target in sickle cell disease. Curr Res Toxicol. 2024;7:100181. https://doi.org/10.1016/j.crtox.2024.100181.
DiMartino LD, Baumann AA, Hsu LL, Kanter J, Gordeuk VR, Glassberg J, et al; Sickle Cell Disease Implementation Consortium. The sickle cell disease implementation consortium: Translating evidence-based guidelines into practice for sickle cell disease. Am J Hematol. 2018;93(12):E391-E395. https://doi.org/10.1002/ajh.25282.
Garcia-Casal MN, Pasricha SR, Martinez RX, Lopez-Perez L, Peña-Rosas JP. Serum or plasma ferritin concentration as an index of iron deficiency and overload. Cochrane Database Syst Rev. 2021;5(5): Cd011817. https://doi.org/10.1002/14651858.CD011817.
Feld JJ, Kato GJ, Koh C, Shields T, Hildesheim M, Kleiner DE, et al. Liver injury is associated with mortality in sickle cell disease. Aliment Pharmacol Ther. 2015;42(7):912-921. https://doi.org/10.1111/apt.13347.
Verduzco LA, Nathan DG. Sickle cell disease and stroke. Blood. 2009;114(25):5117- 5125. https://doi.org/10.1182/blood-2009-05-220921.
Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014;312(10):1033-1048. https://doi.org/10.1001/jama.2014.10517. Erratum in: JAMA. 2015;313(7):729.
Estcourt LJ, Hopewell S, Trivella M, Hambleton IR, Cho G. Regular long-term red blood cell transfusions for managing chronic chest complications in sickle cell disease. Cochrane Database Syst Rev. 2019;2019(10):CD008360. https://doi.org/10.1002/14651858.cd008360.pub5.
Brunson A, Lei A, Rosenberg AS, White RH, Keegan T, Wun T. Increased incidence of VTE in sickle cell disease patients: risk factors, recurrence and impact on mortality. Br J Haematol. 2017;178(2):319-326. https://doi.org/10.1111/bjh.14655.
Naik RP, Streiff MB, Haywood C, Nelson JA, Lanzkron S. Venous Thromboembolism in Adults with Sickle Cell Disease: A serious and under-recognized complication. Am J Med. 2013;126(5):443-449. https://doi.org/10.1016/j.amjmed.2012.12.016.
Ma H, Huang Y, Tian W, Liu J, Yan X, Ma L, Lai J. Endothelial transferrin receptor 1 contributes to thrombogenesis through cascade ferroptosis. Redox Biol. 2024; 70:103041. https://doi.org/10.1016/j.redox.2024.103041.
Gladwin MT, Sachdev V. Cardiovascular abnormalities in sickle cell disease. J Am Coll Cardiol. 2012;59 (13):1123-1133. https://doi.org/10.1016/j.jacc.2011.10.900.
Gladwin MT, Barst RJ, Gibbs JS, Hildesheim M, Sachdev V, Nouraie M, et al, walk-PHaSST Investigators and Patients. Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom. PLoS One. 2014;9(7):e99489. https://doi.org/10.1371/journal.pone.0099489.
Adam SS, Flahiff CM, Kamble S, Telen MJ, Reed SD, De Castro LM. Depression, quality of life, and medical resource utilization in sickle cell disease. Blood Adv. 2017;1(23):1983-1992. https://doi.org/10.1182/bloodadvances.2017006940
Kang H, Han M, Xue J, Baek Y, Chang J, Hu S, et al. Renal clearable nanochelators for iron overload therapy. Nat Commun 2019;10(1):5134. https://doi.org/10.1038/s41467-019-13143-z.
Li S, Han Q, Liu C, Wang Y, Liu F, Pan S, et al. Role of ferroptosis in chronic kidney disease. Cell Commun Signal. 2024;22(1):113. https://doi.org/10.1186/s12964-023-01422-8.
Wilson SR, Sears M, Williams E, Drapekin J, Sivakumar I, Padrino S, et al. GR-NDaD investigators. Gaps in the diagnosis and management of iron overload in sickle cell disease: a ‘real-world’ report from the GRNDaD registry. Br J Haematol. 2021;195(5):e157-e160. https://doi.org/10.1111/bjh.17762.
Puliyel M, Sposto R, Berdoukas VA, Hofstra TC, Nord A, Carson S, et al. Ferritin trends do not predict changes in total body iron in patients with transfusional iron overload. Am J Hematol. 2014;89(4):391-394. https://doi.org/10.1002/ajh.23650.
Cippà PE, Boucsein I, Adams H, Krayenbuehl PA. Estimating Iron Overload in Patients with Suspected Liver Disease and Elevated Serum Ferritin. Am J Med. 2014;127(10):1011.e1-1011.e3. https://doi.org/10.1016/j.amjmed.2014.03.016.
Ginès P, Castera L, Lammert F, Graupera I, Serra-Burriel M, Allen AM, et al. LiverScreen Consortium Investigators. Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases. Hepatology. 2022;75(1):219-228. https://doi.org/10.1002/hep.32163.
Porter J, Bowden DK, Economou M, Troncy J, Ganser A, Habr D, et al. Health-Related Quality of Life, Treatment Satisfaction, Adherence and Persistence in β-Thalassemia and Myelodysplastic Syndrome Patients with Iron Overload Receiving Deferasirox: Results from the EPIC Clinical Trial. Anemia. 2012;2012:297641. https://doi.org/10.1155/2012/297641.
Chou ST, Alsawas M, Fasano RM, Field JJ, Hendrickson JE, Howard J, et al. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv. 2020; 28;4(2):327-355. https://doi.org/10.1182/bloodadvances.2019001143.
Harmatz P, Butensky E, Quirolo K, Williams R, Ferrell L, Moyer T, et al. Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy. Blood. 2000;96(1):76- 79. https://doi.org/10.1182/blood.V96.1.76.
Theocharidou E, Suddle AR. The Liver in Sickle Cell Disease. Clin Liver Dis. 2019;23(2):177-189. https://doi.org/10.1016/j.cld.2018.12.002.
Coates TD, Wood JC. How we manage iron overload in sickle cell patients. Br J Haematol. 2017;177(5):703-716. https://doi.org/10.1111/bjh.14575.
Badawy SM, Liem RI, Rigsby CK, Labotka RJ, DeFreitas RA, Thompson AA. Assessing cardiac and liver iron overload in chronically transfused patients with sickle cell disease. Br J Haematol. 2016;175(4):705- 713. https://doi.org/10.1111/bjh.14277.
Porter J, Garbowski M. Consequences and management of iron overload in sickle cell disease. Hematology Am Soc Hematol Educ Program. 2013;2013(1):447-456. https://doi.org/10.1182/asheducation-2013.1.447.
Noetzli LJ, Coates TD, Wood JC. Pancreatic iron loading in chronically transfused sickle cell disease is lower than in thalassaemia major. Br J Haematol. 2011;152(2):229-233. https://doi.org/10.1111/j.1365-2141.2010.08476.x.
Marsella M, Borgna-Pignatti C. Transfusional iron overload and iron chelation therapy in thalassemia major and sickle cell disease. Hematol Oncol Clin North Am 2014;28(4):703-727, vi. https://doi.org/10.1016/j.hoc.2014.04.004.
Fung EB, Harmatz P, Milet M, Ballas SK, De Castro L, Hagar W, et al; MultiCenter Study of Iron Overload Research Group. Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: A report from the multi-center study of iron overload. Am J Hematol. 2007;82(4):255-265. https://doi.org/10.1002/ajh.20809.
Ballas SK. Iron overload is a determinant of morbidity and mortality in adult patients with sickle cell disease. Semin Hematol. 2001;38 (1 Suppl 1):30-36. https://doi.org/10.1016/S0037-1963(01)90058-7.
Njoku F, Pugh N, Brambilla D, Kroner B, Shah N, Treadwell M, et al. Mortality in adults with sickle cell disease: Results from the sickle cell disease implementation consortium (SCDIC) registry. Am J Hematol. 2024;99(5):900-909. https://doi.org/10.1002/ajh.27279.
Piel FB, Jobanputra M, Gallagher M, Weber J, Laird SG, McGahan M. Co-morbidities and mortality in patients with sickle cell disease in England: A 10-year cohort analysis using hospital episodes statistics (HES) data. Blood Cells Mol Dis. 2021; 89:102567. https://doi.org/10.1016/j.bcmd.2021.102567.
Webb J, Kwiatkowski JL. Stroke in patients with sickle cell disease. Expert Rev Hematol. 2013;6(3):301-316. https://doi.org/10.1586/ehm.13.25.
van Tuijn CFJ, Schimmel M, Van Beers EJ, Nur E, Biemond BJ. Prospective evaluation of chronic organ damage in adult sickle cell patients: A seven‐year follow‐up study. Am J Hematol. 2017;92(10):E584-E590. https://doi.org/10.1002/ajh.24855.
Fortuna V, Lima J, Oliveira GF, Oliveira YS, Getachew B, Nekhai S, et al. Ferroptosis as an emerging target in sickle cell disease. Curr Res Toxicol. 2024;7:100181. https://doi.org/10.1016/j.crtox.2024.100181.
DiMartino LD, Baumann AA, Hsu LL, Kanter J, Gordeuk VR, Glassberg J, et al; Sickle Cell Disease Implementation Consortium. The sickle cell disease implementation consortium: Translating evidence-based guidelines into practice for sickle cell disease. Am J Hematol. 2018;93(12):E391-E395. https://doi.org/10.1002/ajh.25282.
Garcia-Casal MN, Pasricha SR, Martinez RX, Lopez-Perez L, Peña-Rosas JP. Serum or plasma ferritin concentration as an index of iron deficiency and overload. Cochrane Database Syst Rev. 2021;5(5): Cd011817. https://doi.org/10.1002/14651858.CD011817.
Feld JJ, Kato GJ, Koh C, Shields T, Hildesheim M, Kleiner DE, et al. Liver injury is associated with mortality in sickle cell disease. Aliment Pharmacol Ther. 2015;42(7):912-921. https://doi.org/10.1111/apt.13347.
Verduzco LA, Nathan DG. Sickle cell disease and stroke. Blood. 2009;114(25):5117- 5125. https://doi.org/10.1182/blood-2009-05-220921.
Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014;312(10):1033-1048. https://doi.org/10.1001/jama.2014.10517. Erratum in: JAMA. 2015;313(7):729.
Estcourt LJ, Hopewell S, Trivella M, Hambleton IR, Cho G. Regular long-term red blood cell transfusions for managing chronic chest complications in sickle cell disease. Cochrane Database Syst Rev. 2019;2019(10):CD008360. https://doi.org/10.1002/14651858.cd008360.pub5.
Brunson A, Lei A, Rosenberg AS, White RH, Keegan T, Wun T. Increased incidence of VTE in sickle cell disease patients: risk factors, recurrence and impact on mortality. Br J Haematol. 2017;178(2):319-326. https://doi.org/10.1111/bjh.14655.
Naik RP, Streiff MB, Haywood C, Nelson JA, Lanzkron S. Venous Thromboembolism in Adults with Sickle Cell Disease: A serious and under-recognized complication. Am J Med. 2013;126(5):443-449. https://doi.org/10.1016/j.amjmed.2012.12.016.
Ma H, Huang Y, Tian W, Liu J, Yan X, Ma L, Lai J. Endothelial transferrin receptor 1 contributes to thrombogenesis through cascade ferroptosis. Redox Biol. 2024; 70:103041. https://doi.org/10.1016/j.redox.2024.103041.
Gladwin MT, Sachdev V. Cardiovascular abnormalities in sickle cell disease. J Am Coll Cardiol. 2012;59 (13):1123-1133. https://doi.org/10.1016/j.jacc.2011.10.900.
Gladwin MT, Barst RJ, Gibbs JS, Hildesheim M, Sachdev V, Nouraie M, et al, walk-PHaSST Investigators and Patients. Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom. PLoS One. 2014;9(7):e99489. https://doi.org/10.1371/journal.pone.0099489.
Adam SS, Flahiff CM, Kamble S, Telen MJ, Reed SD, De Castro LM. Depression, quality of life, and medical resource utilization in sickle cell disease. Blood Adv. 2017;1(23):1983-1992. https://doi.org/10.1182/bloodadvances.2017006940
Kang H, Han M, Xue J, Baek Y, Chang J, Hu S, et al. Renal clearable nanochelators for iron overload therapy. Nat Commun 2019;10(1):5134. https://doi.org/10.1038/s41467-019-13143-z.
Li S, Han Q, Liu C, Wang Y, Liu F, Pan S, et al. Role of ferroptosis in chronic kidney disease. Cell Commun Signal. 2024;22(1):113. https://doi.org/10.1186/s12964-023-01422-8.
Wilson SR, Sears M, Williams E, Drapekin J, Sivakumar I, Padrino S, et al. GR-NDaD investigators. Gaps in the diagnosis and management of iron overload in sickle cell disease: a ‘real-world’ report from the GRNDaD registry. Br J Haematol. 2021;195(5):e157-e160. https://doi.org/10.1111/bjh.17762.
Puliyel M, Sposto R, Berdoukas VA, Hofstra TC, Nord A, Carson S, et al. Ferritin trends do not predict changes in total body iron in patients with transfusional iron overload. Am J Hematol. 2014;89(4):391-394. https://doi.org/10.1002/ajh.23650.
Cippà PE, Boucsein I, Adams H, Krayenbuehl PA. Estimating Iron Overload in Patients with Suspected Liver Disease and Elevated Serum Ferritin. Am J Med. 2014;127(10):1011.e1-1011.e3. https://doi.org/10.1016/j.amjmed.2014.03.016.
Ginès P, Castera L, Lammert F, Graupera I, Serra-Burriel M, Allen AM, et al. LiverScreen Consortium Investigators. Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases. Hepatology. 2022;75(1):219-228. https://doi.org/10.1002/hep.32163.
Porter J, Bowden DK, Economou M, Troncy J, Ganser A, Habr D, et al. Health-Related Quality of Life, Treatment Satisfaction, Adherence and Persistence in β-Thalassemia and Myelodysplastic Syndrome Patients with Iron Overload Receiving Deferasirox: Results from the EPIC Clinical Trial. Anemia. 2012;2012:297641. https://doi.org/10.1155/2012/297641.
Publicado
2025-12-08
Cómo citar
Vizcaíno, G., Abrams, C. M., Foster, C. B., Flórez, H., Dávila, N., & Rainey, S. C. (2025). The burden of iron overload in sickle cell disease: insights from South Carolina, USA.: La sobrecarga de hierro en la anemia falciforme: perspectivas desde Carolina del Sur, EEUU. Investigación Clínica, 66(4), 378-389. https://doi.org/10.54817/IC.v66n4a03
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