Iron Dysregulation in Sickle Cell Disease: Trend and Clinical Implications

Dr. Bashir Abdrhman Bashir

doi:10.55640/ijmsdh-11-10-10

Open Access

Iron Dysregulation in Sickle Cell Disease: Trend and Clinical Implications

Vol. 11 No. 10 (2025): Volume 11 Issue 10 | Pages: 93-100 | https://doi.org/10.55640/ijmsdh-11-10-10

Authors

Dr. Bashir Abdrhman Bashir
Associate Professor of Hematology / Consultant of Medical Laboratory Sciences Port Sudan Ahlia University, Faculty of Medical Laboratory Sciences, Port Sudan, Sudan
https://orcid.org/0000-0002-5089-9531

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Published Date: 2025-10-18
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Dr. Bashir Abdrhman Bashir. (2025). Iron Dysregulation in Sickle Cell Disease: Trend and Clinical Implications. International Journal of Medical Science and Dental Health, 11(10), 93-100. https://doi.org/10.55640/ijmsdh-11-10-10

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Abstract

Iron imbalance in sickle cell disease (SCD) is a complex puzzle that leads to persistent hemolysis, recurrent transfusions, and dysregulated iron metabolism. This brief review examines the key trends in iron homeostasis, overload, and deficiency in SCD, exploring the underlying mechanisms, clinical implications, and therapeutic approaches. Iron overload frequently arises from transfusion therapy, although iron shortage may also result from heightened erythropoietic demand and inflammation. We highlight the functions of serum ferritin, transferrin saturation (TSAT), hepcidin, and new biomarkers, as well as therapeutic strategies encompassing chelation and innovative treatments. This review synthesizes current findings, identifies knowledge gaps, and suggests future research directions to enhance iron-related outcomes in sickle cell disease (SCD).

Keywords:

Sickle cell disease, iron overload, iron deficiency, transfusion, chelation therapy, hemolysis, Iron, Ferritin, TSAT

References

Kato GJ, Piel FB, Reid CD, Gaston MH, Ohene-Frempong K, Krishnamurti L, Smith WR, Panepinto JA, Weatherall DJ, Costa FF, Vichinsky EP. Sickle cell disease. Nat Rev Dis Primers. 2018 Mar 15;4:18010. doi: 10.1038/nrdp.2018.10. PMID: 29542687.

Minniti C, Brugnara C, Steinberg MH. HbSC disease: A time for progress. Am J Hematol. 2022 Nov;97(11):1390-1393. doi: 10.1002/ajh.26702. Epub 2022 Sep 8. PMID: 36073655.[3] Tebbi CK. Sickle cell disease, a review. Hemato. 2022;3(2):341-366.

Luzzatto L. Sickle cell anaemia and malaria. Mediterr J Hematol Infect Dis. 2012;4(1):e2012065. doi: 10.4084/MJHID.2012.065. Epub 2012 Oct 3. PMID: 23170194; PMCID: PMC3499995.

Centers for Disease Control and Prevention. Data and Statistics on Sickle Cell Disease. July 6, 2023. Accessed September 15, 2023. https://www.cdc.gov/ncbddd/sicklecell/data.html.

McGann PT. Sickle cell anemia: an underappreciated and unaddressed contributor to global childhood mortality. J Pediatr. 2014 Jul;165(1):18-22. doi: 10.1016/j.jpeds.2014.01.070. Epub 2014 Mar 12. PMID: 24630351.

Salinas Cisneros G, Thein SL. Recent Advances in the Treatment of Sickle Cell Disease. Front Physiol. 2020 May 20;11:435. doi: 10.3389/fphys.2020.00435. PMID: 32508672; PMCID: PMC7252227.

Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010 Dec 11;376(9757):2018-31. doi: 10.1016/S0140-6736(10)61029-X. Epub 2010 Dec 3. PMID: 21131035.

Kontoghiorghes GJ. Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications. Int J Mol Sci. 2023 Aug 18;24(16):12928. doi: 10.3390/ijms241612928. PMID: 37629109; PMCID: PMC10454416.

Coates TD, Wood JC. How we manage iron overload in sickle cell patients. Br J Haematol. 2017 Jun;177(5):703-716. doi: 10.1111/bjh.14575. Epub 2017 Mar 14. PMID: 28295188; PMCID: PMC5444974.

McDowell LA, Kudaravalli P, Chen RJ, et al. Iron Overload. [Updated 2024 Jan 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/sites/books/NBK526131/.

Guo S, Frazer DM, Anderson GJ. Iron homeostasis: transport, metabolism, and regulation. Curr Opin Clin Nutr Metab Care. 2016 Jul;19(4):276-81. doi: 10.1097/MCO.0000000000000285. PMID: 27137899.

Coates TD. Management of iron overload: lessons from transfusion-dependent hemoglobinopathies. Blood. 2025 Jan 23;145(4):359-371. doi: 10.1182/blood.2023022502. PMID: 39293029.

Porter J, Garbowski M. Consequences and management of iron overload in sickle cell disease. Hematology Am Soc Hematol Educ Program. 2013;2013:447-56. doi: 10.1182/asheducation-2013.1.447. PMID: 24319218.

Pfeiffer CM, Looker AC. Laboratory methodologies for indicators of iron status: strengths, limitations, and analytical challenges. Am J Clin Nutr. 2017 Dec;106(Suppl 6):1606S-1614S. doi: 10.3945/ajcn.117.155887. Epub 2017 Oct 25. PMID: 29070545; PMCID: PMC5701713.

Nekhai S, Xu M, Foster A, Kasvosve I, Diaz S, Machado RF, Castro OL, Kato GJ, Taylor JG 6th, Gordeuk VR. Reduced sensitivity of the ferroportin Q248H mutant to physiological concentrations of hepcidin. Haematologica. 2013 Mar;98(3):455-63. doi: 10.3324/haematol.2012.066530. Epub 2012 Oct 12. PMID: 23065513; PMCID: PMC3659936.

Mariani R, Trombini P, Pozzi M, Piperno A. Iron metabolism in thalassemia and sickle cell disease. Mediterr J Hematol Infect Dis. 2009 Oct 27;1(1):e2009006. doi: 10.4084/MJHID.2009.006. PMID: 21415988; PMCID: PMC3033158.

Gomez S, Diawara A, Gbeha E, Awadalla P, Sanni A, Idaghdour Y, Rahimy MC. Comparative Analysis of Iron Homeostasis in Sub-Saharan African Children with Sickle Cell Disease and Their Unaffected Siblings. Front Pediatr. 2016 Feb 23;4:8. doi: 10.3389/fped.2016.00008. PMID: 26942167; PMCID: PMC4762986.

Ginzburg YZ. Hepcidin and its multiple partners: Complex regulation of iron metabolism in health and disease. Vitam Horm. 2023;123:249-284. doi: 10.1016/bs.vh.2023.03.001. Epub 2023 Mar 30. PMID: 37717987.

Omena J, Cople-Rodrigues CDS, Cardoso JDDA, Soares AR, Fleury MK, Brito FDSB, Koury JC, Citelli M. Serum Hepcidin Concentration in Individuals with Sickle Cell Anemia: Basis for the Dietary Recommendation of Iron. Nutrients. 2018 Apr 17;10(4):498. doi: 10.3390/nu10040498. PMID: 29673144; PMCID: PMC5946283.

Valentini CG, Teofili L, Gehrie E. Iron metabolism in sickle cell disease patients undergoing chronic red blood cell exchange: A delicate homeostasis in balance. Br J Haematol. 2024 Oct;205(4):1257-1259. doi: 10.1111/bjh.19703. Epub 2024 Aug 11. PMID: 39128849.

Ras-Jiménez MDM, Ramos-Polo R, Francesch Manzano J, Corbella Santano M, Morillas Climent H, Jose-Bazán N, Jiménez-Marrero S, Garcimartin Cerezo P, Yun Viladomat S, Moliner Borja P, Torres Cardús B, Verdú-Rotellar JM, Diez-López C, González-Costello J, García-Romero E, de Frutos Seminario F, Triguero-Llonch L, Enjuanes Grau C, Tajes Orduña M, Comin-Colet J. Soluble Transferrin Receptor as Iron Deficiency Biomarker: Impact on Exercise Capacity in Heart Failure Patients. J Pers Med. 2023 Aug 21;13(8):1282. doi: 10.3390/jpm13081282. PMID: 37623532; PMCID: PMC10455097.

Alkindi S, Panjwani V, Al-Rahbi S, Al-Saidi K, Pathare AV. Iron Overload in Patients With Heavily Transfused Sickle Cell Disease-Correlation of Serum Ferritin With Cardiac T2* MRI (CMRTools), Liver T2* MRI, and R2-MRI (Ferriscan®). Front Med (Lausanne). 2021 Oct 25;8:731102. doi: 10.3389/fmed.2021.731102. PMID: 34760898; PMCID: PMC8573209.

Aslan E, Luo JW, Lesage A, Paquin P, Cerny M, Chin AS, Olivié D, Gilbert G, Soulières D, Tang A. MRI-based R2* mapping in patients with suspected or known iron overload. Abdom Radiol (NY). 2021 Jun;46(6):2505-2515. doi: 10.1007/s00261-020-02912-w. Epub 2021 Jan 2. PMID: 33388804.

Badawy SM, Payne AB, Hulihan MM, Coates TD, Majumdar S, Smith D, Thompson AA. Concordance with comprehensive iron assessment, hepatitis A vaccination, and hepatitis B vaccination recommendations among patients with sickle cell disease and thalassaemia receiving chronic transfusions: an analysis from the Centers for Disease Control haemoglobinopathy blood safety project. Br J Haematol. 2021 Dec;195(5):e160-e164. doi: 10.1111/bjh.17798. Epub 2021 Aug 24. PMID: 34431082; PMCID: PMC8627444.

Reddy NS, Vagha K, Varma A, Javvaji CK. A Study of the Clinical Profile of Iron Deficiency Anemia in Children With Sickle Cell Disease in a Tertiary Care Center. Cureus. 2024 Sep 24;16(9):e70087. doi: 10.7759/cureus.70087. PMID: 39449937; PMCID: PMC11501420.

Mangaonkar AA, Thawer F, Son J, Ajebo G, Xu H, Barrett NJ, Wells LG, Bowman L, Clair B, Patel N, Bora P, Jung G, Nemeth E, Kutlar A. Regulation of iron homeostasis through the erythroferrone-hepcidin axis in sickle cell disease. Br J Haematol. 2020 Jun;189(6):1204-1209. doi: 10.1111/bjh.16498. Epub 2020 Feb 6. PMID: 32030737; PMCID: PMC8011855.

Hoenemann C, Ostendorf N, Zarbock A, Doll D, Hagemann O, Zimmermann M, Luedi M. Reticulocyte and Erythrocyte Hemoglobin Parameters for Iron Deficiency and Anemia Diagnostics in Patient Blood Management. A Narrative Review. J Clin Med. 2021 Sep 19;10(18):4250. doi: 10.3390/jcm10184250. PMID: 34575361; PMCID: PMC8470754.

Koren A, Fink D, Admoni O, Tennenbaum-Rakover Y, Levin C. Non-transferrin-bound labile plasma iron and iron overload in sickle-cell disease: a comparative study between sickle-cell disease and beta-thalassemic patients. Eur J Haematol. 2010 Jan 1;84(1):72-8. doi: 10.1111/j.1600-0609.2009.01342.x. PMID: 19732137.

Larissi K, Politou M, Margeli A, Poziopoulos C, Flevari P, Terpos E, Papassotiriou I, Voskaridou E. The Growth Differentiation Factor-15 (GDF-15) levels are increased in patients with compound heterozygous sickle cell and beta-thalassemia (HbS/βthal), correlate with markers of hemolysis, iron burden, coagulation, endothelial dysfunction and pulmonary hypertension. Blood Cells Mol Dis. 2019 Jul;77:137-141. doi: 10.1016/j.bcmd.2019.04.011. Epub 2019 Apr 23. PMID: 31071550.

Castro OL, De Franceschi L, Ganz T, Kanter J, Kato GJ, Pasricha SR, Rivella S, Wood JC. Iron restriction in sickle cell disease: When less is more. Am J Hematol. 2024 Jul;99(7):1349-1359. doi: 10.1002/ajh.27267. Epub 2024 Feb 23. PMID: 38400590.

Pinto VM, Mazzi F, De Franceschi L. Novel therapeutic approaches in thalassemias, sickle cell disease, and other red cell disorders. Blood. 2024 Aug 22;144(8):853-866. doi: 10.1182/blood.2023022193. PMID: 38820588.

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Iron Dysregulation in Sickle Cell Disease: Trend and Clinical Implications

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Dr. Bashir Abdrhman Bashir

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