Biochemical evaluation of iron metabolism: The diagnostic role of hepcidin and soluble transferrin receptor in anemia

Abstract

Background: Accurate biochemical classification of Anemia is often restricted due to the inflammatory confounding of traditional Iron indices. Serum ferritin may be increased as an acute-phase reactant whereas transferrin saturation (TSAT) may be decreased during both absolute iron deficiency and restriction secondary to inflammation. Hepcidin and soluble transferrin receptor (sTfR) offer mechanistically different signals that might serve to enable a better distinction between iron deficiency anemia (IDA), anemia of inflammation (AI) and mixed anemia. Objective: To assess the diagnostic value of hepcidin and sTfR (alone and in combination) in differential diagnosis of the anemia phenotypes, and for the identification of IDA. Methods: A cross-sectional study of the diagnostic accuracy was performed among 100 anemia cases recruited from Imam Al-Sadiq Hospital as well as private outpatient clinics in Babylon Governorate of Iraq from October 2025 to February 2026. Demographic/ clinical data was recorded. Laboratory testing consisted of CBC, serum iron, TIBC, TSAT, ferritin, CRP, hepcidin and sTfR. An estimate of the sTfR/log10 (ferritin) ratio was generated. Anemia phenotypes (IDA, AI, mixed) have been assigned on the basis of a predefined composite standard of reference based on the traditional iron studies according to the state of inflammation (CRP). Appropriate parametric/nonparametric tests were used for group comparisons. Correlations between biomarkers with Spearman's correlations were done. Diagnostic accuracy to assess IDA (IDA vs non-IDA) was assessed using ROC analysis and multivariable logistic regression was performed for independent associations using IDA. Results: Out of 100 cases were IDA (45%) (n=45) cases, AI (35%) (n=35) and Mixed (20%) (n=20) cases. Mean age was found to be significantly different (IDA 31.9±10.4 years; AI 54.9±13.9; mixed 49.7±9.0; p