Optimal Reticulocyte Hemoglobin Equivalent Cutoff to Diagnose Iron Deficiency: A Study from South Indian Population

Abstract Background: Anemia is the most common health problem affecting approximately one-third of the population worldwide, with 50% of patients suffering from iron-deficiency anemia (IDA). Hematological parameters along with peripheral smear finding may help in picking up patients with IDA but are insensitive to early stages of iron deficiency. Serum iron studies are required for confirmation but these are affected by inflammation, infection, and liver disease. Reticulocyte hemoglobin equivalent (Ret He) measures the hemoglobin (HGB) content in circulating reticulocytes, reflecting iron availability for erythropoiesis over the preceding 3–4 days and it is not influenced by inflammation or diurnal variation and provides a real-time assessment of iron deficiency. However, Ret He cutoff show variation across different population. Methods: This cross-sectional study done at a tertiary care health center in South India, for the period of 2 years (September 2024–February 2026). The study population includes individuals more than 18 years of age and is categorized into two categories. Category I composed of 100 normal individuals with HGB values and serum iron studies within normal limits. Category II comprising of 200 individuals having serum ferritin levels <30 ng/mL or transferrin saturation (T-SAT) of <20%. Results: Comparison of the mean values of parameters such as HGB, red blood cell (RBC) count, RBC indices, reticulocyte parameters, Ret He, serum iron, T-SAT, and serum ferritin levels were reduced below normal limits in cases with iron deficiency. A strong statistically significant positive correlation is observed with mean corpuscular hemoglobin (r = 0.823), mean corpuscular volume (r = 0.8186), and HGB (r = 0.8165). Moderate positive correlations are evident with key iron profile parameters, including T-SAT%, serum iron, and ferritin. Receiver operating characteristic analysis Ret He cutoff of 29.85 pg was obtained which showed 85% sensitivity and 88% specificity with excellent area under the curve of 0.941 and statistically significant P < 0.001 in predicting iron deficiency. Conclusion: Reticulocyte hemoglobin equivalent (Ret-He) is a reliable and effective marker for detecting iron deficiency, demonstrating excellent diagnostic accuracy, with a cutoff of 29.85 pg. Its incorporation into routine hematological evaluation may facilitate early identification of iron deficiency, although population-specific cutoffs should be considered.