Serum Hepcidin Is an Early Predictor of Iron Depletion in Non-Anemic Blood Donors
Authors: Arunphong Khetwasan , Hantrakool Sasinee , Koonyosying Pimpisid , Sriwichai Maitree , Shaengkhamnang Banphot , Leetrakool Nipapan , Niprapan Piangrawee , Punnachet Teerachat , Hantrakun Nonthakorn , Piriyakhuntorn Pokpong , Rattanathammethee Thanawat , Chai-Adisaksopha Chatree , Rattarittamrong Ekarat , Tantiworawit Adisak , Norasetthada Lalita , Srichairatanakool Somdet 
Published: December 2023

Introduction
Iron deficiency is one of the major concerns in repeated whole blood donors. Although taking iron supplementation, frequent whole blood donors sometimes suffer from iron depletion which contributes to adverse impact on donor's health and may reduce the donor blood pool. Laboratory parameters identifying iron depleted status could help early recognize donors at risk of iron deficiency. Hepcidin is a key iron regulator, which blocks ferroportin to inhibit iron absorption and iron release from hepatocytes. In iron depletion, hepcidin down regulates to encourage iron absorption. Previous data reported that serum hepcidin at less than 10 ng/mL was significantly associated with iron deficiency. According to the biological function and physiological response of hepcidin, we hypothesize that hepcidin could be an early predictor of iron deficiency status in non-anemic individuals.
Methods
This cross-sectional study was conducted at the Blood Bank Center at Chiang Mai University Hospital, Chiang Mai, Thailand in May 2023. After the informed consent was obtained, ninety-seven healthy repeated whole blood donors who had donated blood at least twice in the past year were recruited. The medical records were reviewed. Basic characteristics and laboratories including complete blood count, reticulocyte indices, iron parameters, and serum hepcidin were evaluated. Donors who had serum ferritin level less than 30 and 30-100 ng/mL were categorized as iron deficiency, and low ferritin group, respectively. Those who had ferritin more than 100 ng/mL were the control group. Logistic regression analysis was done to determine the value of serum hepcidin in predicting iron deficiency status in each group.
Results
The total of 97 repeated whole blood donors were recruited, 48 (49.5%) were women. Mean age was 34.6 ± 10.7 years. There were 8 donors in the iron deficiency group, 38 in the low ferritin group, and 51 donors in the control group. Mean hemoglobin levels were 13.4 ± 1.1, 13.8 ± 1.2, and 14.2 ± 1.2 g/dL in the iron deficiency, low ferritin group and control, respectively, (p = 0.796). White blood cell and platelet count were not different in these groups. Similarly, red cell indices including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), and reticulocyte indices showed no difference among groups. Serum hepcidin had a significant difference between the three groups. Median levels of hepcidin were 2.61 (1.37, 3.4) and 12.35 (10.12, 15.57) ng/mL in the iron deficiency and the low ferritin group, respectively, compared to 26.01 (21.36, 39.08) ng/mL in the control group, (p &lt; 0.001). Low serum hepcidin (less than 10 ng/mL) were found in 14 (36.8 %) donors who had ferritin levels less than 100 ng/mL, compared to only 1 (2.4%) donor in the control group, (p &lt; 0.001). In addition, serum hepcidin showed a strong correlation with ferritin levels (r = 0.779). Logistic regression model showed that only female sex (OR: 2.87; 95% CI: 1.26, 6.56) and hepcidin (OR: 0.76; 95% CI: 0.66, 0.86) were significant predictors of repeated donors who were at risk of iron depletion and had the ferritin levels less than 100 ng/mL.
Conclusions
Frequent blood donors are at risk of iron depletion. Serum hepcidin was a significant predictor of iron depleted status in non-anemic donors. Serum hepcidin also showed a significant correlation with ferritin levels. The downregulation of serum hepcidin was detected prior to the changes of red blood cell indices and reticulocyte responses. Early recognition and identification of donors at risk of iron depletion and prompt iron restoration are the key to ensuring the donor safety and preserving adequate blood donor pool.