Diagnostic Utility of Reticulocyte Hemoglobin Equivalent in Iron-Deficiency Anemia: An Observational Study From Eastern India

TL;DR

This study shows that reticulocyte hemoglobin equivalent (Ret-He) is more reliable than serum ferritin for diagnosing iron-deficiency anemia, especially in cases with inflammation.

Contribution

The study demonstrates Ret-He's superior diagnostic accuracy over serum ferritin in iron-deficiency anemia detection, particularly in inflammatory conditions.

Findings

Ret-He had higher diagnostic accuracy (AUC=0.839) compared to serum ferritin (AUC=0.728) in detecting IDA.

Ret-He remained low in both pure IDA and IDA with inflammation, unlike serum ferritin which is elevated in inflammation.

Ret-He at <23.6 pg showed 81.7% sensitivity and 73.2% specificity for IDA diagnosis.

Abstract

Background

Iron deficiency anemia (IDA) continues to be a major global health concern, especially in India. Serum ferritin, a conventional marker for iron deficiency, is considered unreliable in inflammatory conditions. Reticulocyte hemoglobin equivalent (Ret-He) reflects real-time iron availability for erythropoiesis and may overcome this limitation. This study aimed to evaluate the diagnostic efficacy of Ret-He and compare it with serum ferritin in detecting IDA in patients receiving treatment at an Eastern Indian tertiary care facility.

Methods

A hospital-based observational study was conducted at Tata Main Hospital, Jamshedpur, from December 2023 to December 2024. Patients with anemia (hemoglobin <12 g/dL for females and <13 g/dL for males), ≥18 years old, were included in the study. Complete blood count parameters, including Ret-He, were measured using the Sysmex XN-1000 analyzer (Sysmex, Kobe, Japan). IDA was diagnosed based on microcytic hypochromic indices, peripheral smear findings, and serum ferritin <70 ng/mL. Receiver operating characteristic (ROC) curve analysis was done to obtain the optimal cut-off values for serum ferritin and Ret-He and their respective specificity, sensitivity, and diagnostic accuracy; negative and positive predictive values were also calculated. To compare areas under the curve (AUC), the DeLong test was employed.

Results

Among 672 patients (mean age 61.3±17.3 years, 67% females), IDA was diagnosed in 257 (38.2%) patients, including 151 (58.8%) with pure IDA and 106 (41.2%) with IDA and concomitant inflammation. In comparison to non-IDA, Ret-He was considerably lower in IDA (21.0±4.8 vs. 27.6±4.6 pg, p<0.001). ROC analysis demonstrated superior diagnostic performance of Ret-He (AUC=0.839) over serum ferritin (AUC=0.728, p=0.045). At an “optimal cut-off” of <23.6 pg, Ret-He showed 81.7% sensitivity, 73.2% specificity, and 78.4% diagnostic accuracy. Serum ferritin (<39.0 ng/ml) had higher sensitivity (90.6%) but lower specificity (50.0%). Ret-He remained low in both pure IDA and IDA with inflammation, while ferritin was markedly elevated in inflammatory states.

Conclusion

Ret-He demonstrates superior diagnostic accuracy compared to serum ferritin for identifying IDA and remains unaffected by inflammation. Its integration into routine complete blood count analysis offers a cost-effective, reliable approach for early detection of iron deficiency, making it particularly valuable in resource-limited settings and patients with concurrent inflammatory conditions.

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