# Erythroferrone-Driven Regulation of Hepcidin and Iron Levels in Polytransfused Sickle Cell Anaemia Patients: A Prospective Study

## TL;DR

This study shows that high erythroferrone levels in sickle cell anemia patients may lower hepcidin, increasing the risk of iron overload from frequent blood transfusions.

## Contribution

The study identifies a novel regulatory relationship between erythroferrone and hepcidin in polytransfused sickle cell anemia patients.

## Key findings

- SCA patients had significantly higher ERFE and iron-related markers compared to controls.
- ERFE levels were inversely correlated with hepcidin, suggesting a regulatory mechanism.
- Regular transfusions were linked to higher ERFE and ferritin levels in SCA patients.

## Abstract

The interplay of erythroferrone (ERFE), hepcidin, and ferroportin is crucial for ensuring systemic iron homeostasis. This study determined the influence of ERFE on hepcidin and iron levels in polytransfused patients with sickle cell anaemia (SCA). This multicentre case-control study recruited 60 SCA participants and 30 controls (HbA), aged 2–34 years, from Tamale Teaching Hospital; Methodist Hospital, Wenchi; and Seventh Day Adventist Hospital, Sunyani, Ghana, between the periods of March to July 2023. About 4 mL of blood was collected for a full blood count using a haematology analyzer and serum ERFE, hepcidin, ferroportin, and ferritin estimation using an enzyme-linked immunosorbent assay. Data were analyzed using SPSS Version 26.0. ERFE (p < 0.001), ferroportin (p = 0.016), ferritin (p < 0.001), serum iron (p < 0.001), transferrin (p = 0.001), soluble transferrin receptor (sTFR) (p = 0.019), TWBC (p < 0.001), and platelet (p < 0.001) were significantly higher in SCA participants and hydroxyurea-naïve participants than in the control group and hydroxyurea-treated participants, respectively. Levels of hepcidin (p < 0.001), red blood cell (p < 0.001), haemoglobin (p < 0.001), and haematocrit (p < 0.001) were lower in the SCA and hydroxyurea-naïve groups than in the control and hydroxyurea-treated groups, respectively. An inverse correlation was observed between serum ERFE and hepcidin (r = −0.391, p = 0.002) and hepcidin and ferroportin (r = −0.266, p = 0.040), while ferritin (r = 0.439, p < 0.001) and ferroportin (r = 0.309, p = 0.016) showed a positive correlation with ERFE. No correlation was found between serum hepcidin and ferritin levels (r = 0.025, p = 0.853). Again, participants with regular blood transfusions had significantly higher levels of ERFE (p < 0.001) and ferritin (p = 0.002) than those with rare and no transfusions per year. None of the SCA participants had done iron testing. In conclusion, the negative impact of ERFE on hepcidin levels may exacerbate the risk of iron burden, as evident by elevated iron levels in SCA patients and the need for regular monitoring of the iron status of polytransfused SCA patients.