Liver iron overload: Post-transfusion implications
DOI:
https://doi.org/10.59093/27112330.132Keywords:
iron overload, blood transfusion, iron metabolism, iron, liver, chelation therapy, magnetic resonance imaging.Abstract
Post-transfusion iron overload is a common complication in patients with chronic diseases who require regular blood transfusions. Iron does not have a physiological mechanism for excretion, so it primarily accumulates in the liver, which can lead to severe liver damage. Iron homeostasis is regulated through intestinal absorption, but multiple transfusions disrupt this balance, promoting iron accumulation. This excess iron can generate free radicals, triggering oxidative stress and lipid peroxidation, which promote cellular damage in the liver and other organs. This can lead to cirrhosis, liver failure, and hepatocellular carcinoma. Biomarkers such as serum ferritin, transferrin saturation, and liver tissue iron concentration are used to diagnose iron overload. Magnetic resonance imaging is a commonly used method for estimating iron deposits in the liver as well as in other organs, including the heart, pancreas, kidneys, and endocrine glands. The primary treatment is iron chelation therapy, using agents such as deferoxamine, deferasirox, and deferiprone, which facilitate iron elimination from the body. Prevention of iron overload depends on the proper management of multiple transfusions, with a preference for erythrocytapheresis over simple transfusions, avoiding unnecessary iron administration, and using iron chelators when levels are elevated. Future approaches involve the development of more specific and personalized treatments, based on biomarkers and advancements in imaging techniques, which will allow for more precise and less invasive management of iron overload.
Downloads
References
Mancardi D, Mezzanotte M, Arrigo E, Barinotti A, Roetto A. Iron overload, oxidative stress, and ferroptosis in the failing heart and liver. Antioxidants 2021;10:1864. https://doi.org/10.3390/antiox10121864.
Shander A, Cappellini MD, Goodnough LT. Iron overload and toxicity: the hidden risk of multiple blood transfusions. Vox Sang 2009;97:185-197. https://doi.org/10.1111/j.1423-0410.2009.01207.x.
França M, Carvalho JG. MR imaging assessment and quantification of liver iron. Abdom Radiol 2020;45:3400-3412. https://doi.org/10.1007/s00261-020-02574-8.
Hollán S. Iron overload in light of the identification of a haemochromatosis gene. Haematologia 1997;28:109-116.
Deugnier Y, Turlin B. Pathology of hepatic iron overload. World J Gastroenterol 2007; 13:4755-4760. https://doi.org/10.3748/wjg.v13.i35.4755.
Ozment CP, Turi JL. Iron overload following red blood cell transfusion and its impact on disease severity. Biochim Biophys Acta 2009;1790:694-701.
Coates TD. Iron overload in transfusion-dependent patients. Hematology Am Soc Hematol Educ Program 2019; 2019: 337-344. https://doi.org/10.1182/hematology.2019000036.
Feng Q, Yi J, Li T, Liang B, Xu F, Peng P. Narrative review of magnetic resonance imaging in quantifying liver iron load. Front Med 2024;11:1321513. https://doi.org/10.3389/fmed.2024.1321513.
Taher AT, Musallam KM, Inati A. Iron overload: consequences, assessment, and monitoring. Hemoglobin 2009;33:S46-57. https://doi.org/10.3109/03630260903346676.
Taher AT, Musallam KM, Cappellini MD. Thalassemias: From genotype to phenotype. Haematologica 2017;102:462-480. https://doi.org/10.3324/haematol.2017.167643.
Anderson GJ, Frazer DM. Current understanding of iron homeostasis. Am J Clin Nutr 2017;106:1559S-1566S. https://doi.org/10.3945/ajcn.117.155804.
Ganz T, Nemeth E. Iron metabolism: interactions with normal and disordered erythropoiesis. Cold Spring Harb Perspect Med 2012;2:a011668. https://doi.org/10.1101/cshperspect.a011668.
Ito H, Kurokawa H, Matsui H. Mitochondrial reactive oxygen species and heme, non-heme iron metabolism. Arch Biochem Biophys 2021;700:108695. https://doi.org/10.1016/j.abb.2020.108695.
Cazzola M, Della Porta MG, Malcovati L. Clinical relevance of anemia and transfusion iron overload in myelodysplastic syndromes. Hematology Am Soc Hematol Educ Program 2008:166-175. https://doi.org/10.1182/asheducation-2008.1.166.
Fleming RE, Ponka P. Iron overload in human disease. N Engl J Med 2012;366:348-359. https://doi.org/10.1056/NEJMra1004967.
Kohgo Y, Ikuta K, Ohtake T, Torimoto Y, Kato J. Body iron metabolism and pathophysiology of iron overload. Int J Hematol. 2008;88:7-15. https://doi.org/10.1007/s12185-008-0120-5.
Batts KP. Iron overload syndromes and the liver. Mod Pathol 2007;20:S31-39. https://doi.org/10.1038/modpathol.3800715.
Bloomer SA, Brown KE. Iron-induced liver injury: A critical reappraisal. Int J Mol Sci 2019;20:2132. https://doi.org/10.3390/ijms20092132.
Porter JB. Practical management of iron overload. Br J Haematol 2020;191:371-381. https://doi.org/10.1111/bjh.16623.
Hsu CC, Senussi NH, Fertrin KY, Kowdley KV. Iron overload disorders. Hepatol Commun 2022 Aug;6:1842-1854. https://doi.org/10.1002/hep4.2012.
Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 2006;108:2509-2519. https://doi.org/10.1182/blood-2006-03-010777.
Piel FB, Steinberg MH, Rees DC. Sickle cell disease. N Engl J Med 2017;376:1561-1573. https://doi.org/10.1056/NEJMra1510865.
Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, et al. Erythropoietin or darbepoetin for patients with cancer. Cochrane Database Syst Rev 2009;(3):CD003407. https://doi.org/10.1002/14651858.CD007303.pub2.
Ozment CP, Turi JL. Iron overload following red blood cell transfusion and its impact on disease severity. Biochim Biophys Acta 2009;1790:694-701. https://doi.org/10.1016/j.bbagen.2008.09.010.
Brissot P, Brissot E, Loréal O, Ropert M. Laboratory medicine and iron overload: diagnostic and therapeutic. J Lab Precis Med 2020;5:25. https://doi.org/10.21037/jlpm-2019-im-01.
Cazzola M, Della Porta MG, Malcovati L. Clinical relevance of anemia and transfusion iron overload in myelodysplastic syndromes. Hematology Am Soc Hematol Educ Program 2008:166-175. https://doi.org/10.1182/asheducation-2008.1.166.
Fortuna V, Lima J, Oliveira GF, Oliveira YS, Getachew B, Nekhai S, Aschner M, Tizabi Y. Ferroptosis as an emerging target in sickle cell disease. Curr Res Toxicol 2024;7:100181. https://doi.org/10.1016/j.crtox.2024.100181.
Kouroumalis E, Tsomidis I, Voumvouraki A. Iron as a therapeutic target in chronic liver disease. World J Gastroenterol 2023;29:616-655. https://doi.org/10.3748/wjg.v29.i4.616.
Adams PC, Barton JC. Haemochromatosis. Lancet 2007;370:1855-1860. https://doi.org/10.1016/S0140-6736(07)61782-6.
Ghoti H, Rachmilewitz EA, Simon-Lopez R, Gaber R, Katzir Z, Konen E, et al. Evidence for tissue iron overload in long-term hemodialysis patients and the impact of withdrawing parenteral iron. Eur J Haematol 2012;88:229-236. https://doi.org/10.1111/j.1600-0609.2012.01783.x.
Hoffbrand AV, Taher A, Cappellini MD. How I treat transfusional iron overload. Blood 2012;120:3657-69. https://doi.org/10.1182/blood-2012-05-370098.
Omena J, Curioni C, Cople-Rodrigues CS, Citelli M. The effect of food and nutrients on iron overload: what do we know so far? Eur J Clin Nutr 2021;75:1771-1780. https://doi.org/10.1038/s41430-021-00887-5
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;127:1011.e1-3. https://doi.org/10.1016/j.amjmed.2014.03.016.
Angelucci E, Brittenham GM, McLaren CE, Ripalti M, Baronciani D, Giardini C, et al. Hepatic iron concentration and total body iron stores in thalassemia major. N Engl J Med 2000;343:327-331. https://doi.org/10.1056/NEJM200008033430503.
Porter J. Chapter 3: Iron overload: Pathophysiology, diagnosis and monitoring. In: Cappellini MD, Farmakis D, Porter J, et al., editors. 2021 Guidelines: For the management of transfusion dependent thalassaemia (TDT). 4th edition. Nicosia (Cyprus): Thalassaemia International Federation; 2023.
Sohal A, Kowdley KV. A review of new concepts in iron overload. Gastroenterol Hepatol 2024;20:98-107.
Wood JC. Diagnosis and management of transfusion iron overload: the role of imaging. Am J Hematol 2007;82:1132-1135. https://doi.org/10.1002/ajh.21099.
Vasanawala SS, Yu H, Shimakawa A, Jeng M, Brittain JH. Estimation of liver T₂ in transfusion-related iron overload in patients with weighted least squares T₂ IDEAL. Magn Reson Med 2012;67:183-190. https://doi.org/10.1002/mrm.22986.
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;175:705-713. https://doi.org/10.1111/bjh.14277.
Porter JB, Garbowski M. Consequences and management of iron overload in sickle cell disease. Hematol Oncol Clin North Am. 2020;34:451-469.
Cappellini MD, Viprakasit V, Taher AT, Georgiev P, Kuo KHM, Coates T, et al. A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia. N Engl J Med. 2020;382:1219-1231. https://doi.org/10.1056/NEJMoa1910182.
Wood JC, Enriquez C, Ghugre N, Tyzka JM, Carson S, Nelson MD, Coates TD. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood 2005;106:1460-1465. https://doi.org/10.1182/blood-2004-10-3982.
Gandon Y, Olivie D, Guyader D, Aube C, Oberti F, Sebille V, et al. Non-invasive assessment of hepatic iron stores by MRI. Lancet. 2004;363(9406):357-362. https://doi.org/10.1016/S0140-6736(04)15436-6.
Piga A, Perrotta S, Gamberini MR, Voskaridou E, Melpignano A, Filosa A, et al. Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with β-thalassemia. Blood 2019;133:1279-1289. https://doi.org/10.1182/blood-2018-10-879247.
Ganz T. Systemic iron homeostasis. Physiol Rev 2019;99:381-405. https://doi.org/10.1152/physrev.00034.2017.
Macdougall IC, Malyszko J, Hider RC, Bansal SS. Current status of the measurement of blood hepcidin levels in chronic kidney disease. Clin J Am Soc Nephrol. 2019;14:757-766. https://doi.org/10.2215/CJN.13701118.
St Pierre TG, Clark PR, Chua-Anusorn W, Fleming AJ, Jeffrey GP, Olynyk JK, et al. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood 2005;105:855-861. https://doi.org/10.1182/blood-2004-05-1846.
Henninger B, Kremser C, Rauch S, Gschwantler M, Schocke M. Assessment of liver iron overload with T2* relaxation magnetic resonance imaging. Eur Radiol. 2006;16:1892-1897. https://doi.org/10.1007/s00330-006-0193-y.
Cappellini MD, Porter J, El-Beshlawy A. Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias. Haematologica 2019;104:1933-1943. https://doi.org/10.3324/haematol.2018.207324.
Musallam KM, Cappellini MD, Wood JC, Motta I, Graziadei G, Tamim HM, et al. Elevated liver iron concentration is a marker of increased morbidity in patients with β-thalassemia intermedia. Haematologica. 2013;98:1865-1871. https://doi.org/10.3324/haematol.2013.091876.
Anderson LJ, Westwood MA, Holden S, Davis B, Prescott E, Wonke B, et al. Myocardial iron clearance during reversal of siderotic cardiomyopathy with intravenous desferrioxamine: a prospective study using T2* cardiovascular magnetic resonance. Br J Haematol 2001;115:386-392. https://doi.org/10.1046/j.1365-2141.2001.03098.x.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Authors retain all copyright and grant the Colombian Association of Hepatology a non-exclusive right to publish and disseminate their work.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Hepatología’s authorship policy is based on the criteria established by the International Committee of Medical Journal Editors (ICMJE) to credit a person for their work while assigning them responsibility for its publication.
| Article metrics | |
|---|---|
| Abstract views | |
| Galley vies | |
| PDF Views | |
| HTML views | |
| Other views | |
