The Diagnostic Utility of Reticulocyte Hemoglobin in Iron Deficiency Anemia and Early Response Following Intravenous Iron Therapy.

Background and objectives Iron deficiency anemia (IDA) remains a major global health concern, with diagnostic challenges arising from the limitations of traditional biochemical markers. This study aimed to evaluate the diagnostic utility and reliability of reticulocyte hemoglobin (RET-Hb) in identifying IDA and assessing the early functional response, defined as any change in RET-Hb within 48 hours of intravenous iron infusion, as a marker of early marrow iron availability. Specifically, the study sought to assess the percentage change in RET-Hb from baseline following iron infusion. Furthermore, the correlations between RET-Hb and traditional iron indices were evaluated. Methods A single-center combined observational design, including a case-control and longitudinal (within-subject) study, was conducted over 12 months in the Department of General Medicine, All India Institute of Medical Sciences (AIIMS) Bhopal. The study included 200 participants, with 100 patients diagnosed with IDA and 100 healthy controls. RET-Hb and other hematological and biochemical parameters were measured at baseline and at 48 hours after intravenous iron therapy in patients receiving intravenous iron as part of standard care. Statistical analyses included the Shapiro-Wilk test, Spearman's rank correlation, paired t-tests, and receiver operating characteristic (ROC) curve analysis. The diagnostic performance of RET-Hb was also compared with that of serum ferritin, transferrin saturation (TSAT), serum iron, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). Results RET-Hb levels were remarkably lower in IDA patients compared to controls (26.68 ± 4.04 vs. 32.68 ± 1.94 pg; p < 0.001). RET-Hb demonstrated strong positive correlations with serum iron (r = 0.631), serum ferritin (r = 0.672), and TSAT (r = 0.619), and a negative correlation with total iron-binding capacity (TIBC) (r = -0.571). ROC analysis identified a RET-Hb cutoff of 29.65 pg, which predicted IDA with 73% sensitivity and 100% specificity (area under the curve (AUC) = 0.895). RET-Hb increased within 48 hours of treatment, indicating its utility as an early marker of improvement in functional iron availability, preceding measurable changes in hemoglobin (Hb). Overall, 80% of cases demonstrated measurable improvement. The most common category of change was a 1-2 pg increase, observed in 35% of patients, while 14% experienced a rise of more than 5 pg. Conclusions RET-Hb demonstrated good diagnostic performance for identifying IDA in this study and showed an early increase following intravenous iron therapy, suggesting an improvement in functional iron availability. However, because the study compared patients with confirmed IDA with healthy controls, the observed diagnostic performance should be interpreted cautiously and requires validation in more diverse clinical populations.