ORIGINAL ARTICLE
Open Access

Serum Hepcidin Levels as Predictors of Transfusion Requirement in β-Thalassemia Major: Cross-sectional Correlation with Ferritin and Erythropoietic Markers

Thabo M. Nkosi 1, Sipho R. Dlamini 1, Ayesha Patel 2, Michael J. Merwe ORCID 2

1Division of Hematopathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
2Department of Medicine, University of KwaZulu-Natal, Durban, South Africa
DOI: 10.18081/ajbm.2025.4.352

Publication History: Received 02 September 2025, Revised 9 October 2025, Accepted 01 November 2025, Available online 20 November 2025
Copyright: © 2025 Merwe, et al. This is an open-access article under a Creative Commons license (CC BY 4.0).

ABSTRACT

Background

β-Thalassemia major is characterised by ineffective erythropoiesis and lifelong transfusion dependence, leading to progressive iron overload. Although serum ferritin is widely used to assess iron burden, it does not reliably reflect erythropoietic activity or transfusion requirement. Hepcidin, a key regulator of iron homeostasis, is known to be dysregulated in thalassemia; however, its relationship with transfusion burden remains incompletely defined, particularly in African populations.

Objective

To evaluate serum hepcidin levels in patients with β-thalassemia major and to examine their association with transfusion requirement, serum ferritin, and selected erythropoietic markers.

Methods

This cross-sectional study was conducted at tertiary hematology centres in South Africa between January 2023 and December 2024. Patients with confirmed β-thalassemia major receiving regular transfusion therapy were enrolled. Clinical data, transfusion history over the preceding 12 months, and laboratory parameters were collected. Serum hepcidin was measured using enzyme-linked immunosorbent assay, while ferritin and hematologic indices were assessed using standard laboratory methods. Correlation analyses and multivariable regression were performed to identify predictors of transfusion requirement.

Results

Seventy-two patients were included in the analysis. Median serum hepcidin levels were low relative to iron burden, while serum ferritin levels were markedly elevated across the cohort. Serum hepcidin demonstrated a significant inverse correlation with annual transfusion volume and transfusion frequency. In contrast, no consistent correlation was observed between serum hepcidin and ferritin levels. Hepcidin also showed a strong inverse association with reticulocyte count and a positive association with pre-transfusion haemoglobin. In multivariable analysis, serum hepcidin remained an independent predictor of transfusion requirement, whereas ferritin did not.

Conclusion

In UK real-world practice, first-line amivantamab-based therapy demonstrated a clinically meaningful PFS advantage over osimertinib, particularly among patients with MET-associated biology, though OS differences were not yet evident. These findings support the emerging role of early dual EGFR/MET inhibition and highlight the importance of comprehensive molecular profiling to optimise first-line treatment selection. Longer follow-up and prospective studies are warranted to refine sequencing strategies and confirm survival impact.

Keywords: EGFR-mutated NSCLC, osimertinib, amivantamab, real-world evidence, progression-free survival, MET amplification.

Recommended Citation

Thompson E, Carter D, Rahman A. Serum Hepcidin Levels as Predictors of Transfusion Requirement in β-Thalassemia Major:
Cross-sectional Correlation with Ferritin and Erythropoietic Markers. Advanced Journal of Biomedicine & Medicine. 2025;13(4):352-365. doi:10.18081/ajbm.2025.4.352

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.


References

1.      Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V. Guidelines for the Management of Transfusion Dependent Thalassaemia. 4th ed. Thalassaemia International Federation; 2021.

2.      Taher AT, Musallam KM, Cappellini MD. Thalassemia intermedia: an update. Mediterr J Hematol Infect Dis. 2009;1(1):e2009004. doi:10.4084/MJHID.2009.004

3.      Angelucci E, Brittenham GM. Iron-chelating therapy and survival in thalassemia major. N Engl J Med. 2010;363(2):147-156. doi:10.1056/NEJMoa1002554

4.      Ganz T. Hepcidin and iron regulation, 10 years later. Blood. 2011;117(17):4425-4433. doi:10.1182/blood-2011-01-258467

5.      Nemeth E, Ganz T. Regulation of iron metabolism by hepcidin. Annu Rev Nutr. 2006;26:323-342. doi:10.1146/annurev.nutr.26.061505.111303

6.      Rivella S. Ineffective erythropoiesis and thalassemias. Curr Opin Hematol. 2009;16(3):187-194. doi:10.1097/MOH.0b013e32832a1c7a

7.      Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet. 2014;46(7):678-684. doi:10.1038/ng.2996

8.      Tanno T, Bhanu NV, Oneal PA, et al. High levels of GDF15 in thalassemia suppress hepcidin expression. Nat Med. 2007;13(9):1096-1101. doi:10.1038/nm1629

9.      Musallam KM, Taher AT. Iron overload in beta-thalassemia major and intermedia. Hematol Oncol Clin North Am. 2018;32(2):177-193. doi:10.1016/j.hoc.2017.11.002

10.   Origa R, Galanello R, Ganz T, et al. Liver iron concentrations and serum hepcidin in thalassemia. Haematologica. 2007;92(5):583-588. doi:10.3324/haematol.10657

11.   Piperno A, Mariani R, Trombini P, Girelli D. Hepcidin modulation in human diseases. Haematologica. 2009;94(12):163-167. doi:10.3324/haematol.2009.013649

12.   Pasricha SR, Tye-Din J, Muckenthaler MU, Swinkels DW. Iron deficiency. Lancet. 2021;397(10270):233-248. doi:10.1016/S0140-6736(20)32594-0

13.   Kearney SL, Nemeth E, Neufeld EJ, et al. Urinary hepcidin in congenital hemolytic anemias. Blood. 2007;109(10):4144-4149. doi:10.1182/blood-2006-10-051417

14.   Gardenghi S, Grady RW, Rivella S. Anemia, ineffective erythropoiesis, and hepcidin regulation. Blood. 2010;116(19):3783-3791. doi:10.1182/blood-2010-05-286252

15.   Taher AT, Musallam KM, Karimi M, et al. Overview of iron chelation therapy. Transfusion. 2011;51(5):919-928. doi:10.1111/j.1537-2995.2010.02967.x

16.   Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372(19):1832-1843. doi:10.1056/NEJMra1401038

17.   Casu C, Rivella S. Iron chelation and erythropoiesis in thalassemia. Hematology Am Soc Hematol Educ Program. 2014;2014(1):451-458. doi:10.1182/asheducation-2014.1.451

18.   Cappellini MD, Porter JB, Viprakasit V, Taher AT. A paradigm shift on beta-thalassemia treatment. Blood Rev. 2018;32(4):300-311. doi:10.1016/j.blre.2018.02.003

19.   Dussiot M, Maciel TT, Fricot A, et al. An activin receptor IIA ligand trap corrects ineffective erythropoiesis in β-thalassemia. Nat Med. 2014;20(4):398-407. doi:10.1038/nm.3514

20.   Weiss G, Ganz T, Goodnough LT. Anemia of inflammation. Blood. 2019;133(1):40-50. doi:10.1182/blood-2018-06-856500

21.   Makubi A, Roberts DJ. Haemoglobinopathies in sub-Saharan Africa. Br J Haematol. 2020;189(1):111-125. doi:10.1111/bjh.16336

22.   Porter JB, Garbowski MW. Iron overload in sickle cell disease and thalassemia. Hematology Am Soc Hematol Educ Program. 2013;2013(1):447-456. doi:10.1182/asheducation-2013.1.447

23.   Musallam KM, Cappellini MD, Taher AT. Iron overload in β-thalassemia intermedia. Blood Rev. 2012;26(Suppl 1):S16-S19. doi:10.1016/S0268-960X(12)70006-9

24.   Ginzburg YZ, Rivella S. β-thalassemia: a model for dysregulated iron metabolism. Blood. 2011;118(16):4321-4330. doi:10.1182/blood-2011-03-331629

25.   Kattamis A, Papassotiriou I, Palaiologou D, et al. Effect of iron overload on hepcidin levels in thalassemia. Blood Cells Mol Dis. 2009;42(1):1-5. doi:10.1016/j.bcmd.2008.08.007

2025 Vol 13, Issue 4 Pages 352-365

Download article

PDF (519.0 KB) XML (4.5 KB)

Cite this article

Thabo M. Nkosi, Sipho R. Dlamini, Ayesha Patel, Michael J. Merwe (2025). Serum Hepcidin Levels as Predictors of Transfusion Requirement in β-Thalassemia Major: Cross-sectional Correlation with Ferritin and Erythropoietic Markers<br /> . Advanced Journal of Biomedicine & Medicine, 13(4), 352-365. https://doi.org/10.18081/ajbm.2025.4.352
Thabo M. Nkosi, Sipho R. Dlamini, Ayesha Patel, Michael J. Merwe. "Serum Hepcidin Levels as Predictors of Transfusion Requirement in β-Thalassemia Major: Cross-sectional Correlation with Ferritin and Erythropoietic Markers<br /> ." Advanced Journal of Biomedicine & Medicine, vol. 13, no. 4, 2025, pp. 352-365. DOI: 10.18081/ajbm.2025.4.352.
Thabo M. Nkosi, Sipho R. Dlamini, Ayesha Patel, Michael J. Merwe. Serum Hepcidin Levels as Predictors of Transfusion Requirement in β-Thalassemia Major: Cross-sectional Correlation with Ferritin and Erythropoietic Markers<br /> . AJBM. 2025;13(4):352-365. DOI: 10.18081/ajbm.2025.4.352. PMID: .
Thabo M. Nkosi, Sipho R. Dlamini, Ayesha Patel, Michael J. Merwe 2025, "Serum Hepcidin Levels as Predictors of Transfusion Requirement in β-Thalassemia Major: Cross-sectional Correlation with Ferritin and Erythropoietic Markers<br /> ", Advanced Journal of Biomedicine & Medicine, vol. 13, no. 4, pp. 352-365.
@article{thabo2025, title={Serum Hepcidin Levels as Predictors of Transfusion Requirement in β-Thalassemia Major: Cross-sectional Correlation with Ferritin and Erythropoietic Markers<br /> }, author={Thabo M. Nkosi, Sipho R. Dlamini, Ayesha Patel, Michael J. Merwe}, journal={Advanced Journal of Biomedicine & Medicine}, volume={13}, number={4}, pages={352-365}, year={2025}, doi={10.18081/ajbm.2025.4.352} }
TY - JOUR AU - Thabo M. Nkosi, Sipho R. Dlamini, Ayesha Patel, Michael J. Merwe TI - Serum Hepcidin Levels as Predictors of Transfusion Requirement in β-Thalassemia Major: Cross-sectional Correlation with Ferritin and Erythropoietic Markers<br /> JO - American Journal of Biomedicine VL - 13 IS - 4 SP - 352-365 PY - 2025 DO - 10.18081/ajbm.2025.4.352 ER -
%0 Journal Article %A Thabo M. Nkosi, Sipho R. Dlamini, Ayesha Patel, Michael J. Merwe %T Serum Hepcidin Levels as Predictors of Transfusion Requirement in β-Thalassemia Major: Cross-sectional Correlation with Ferritin and Erythropoietic Markers<br /> %J American Journal of Biomedicine %V 13 %N 4 %P 352-365 %D 2025 %R 10.18081/ajbm.2025.4.352 %M
Thabo M. Nkosi, Sipho R. Dlamini, Ayesha Patel, Michael J. Merwe (2025). Serum Hepcidin Levels as Predictors of Transfusion Requirement in β-Thalassemia Major: Cross-sectional Correlation with Ferritin and Erythropoietic Markers<br /> . Advanced Journal of Biomedicine & Medicine, 13(4), 352-365. https://doi.org/10.18081/ajbm.2025.4.352

Article metric