Using Reticulocyte Hemoglobin Equivalent as a Marker for Iron Deficiency and Responsiveness to Iron Therapy

To assess the accuracy of a simplified approach for the diagnosis of iron deficiency anemia (IDA) based on the complete blood cell count (CBC) and reticulocyte analysis.

Five hundred fifty-six consecutive, nonselected patients referred for diagnosis and/or treatment of anemia were included in this diagnostic study to compare the performance of reticulocyte hemoglobin equivalent (RET-He) versus traditional biochemical markers for diagnosis and treatment of IDA. Complete blood count, serum ferritin, iron, and transferrin saturation were performed as clinically indicated. Reticulocyte hemoglobin equivalent was measured with a Sysmex XN-450 analyzer on the residual CBC sample. The study period was from September 20, 2017, through and including November 15, 2018.

Patients (N=556) were studied at baseline, of whom 150 were subsequently treated with intravenous iron. Receiver operating characteristic analysis yielded an RET-He cut-off of 30.7 pg to identify IDA (area under curve, 0.733; 95% CI, 0.692 to 0.775), with 68.2% sensitivity and 69.7% specificity. Patients (n=240) were seen at follow-up, with 57 treated and 183 not treated with intravenous iron. Responsiveness was defined as a hemoglobin increase of ≥1.0 g: a combination of RET-He <28.5 pg and hemoglobin value <10.3 g/dL had 84% sensitivity and 78% specificity as response predictor (area under the curve, 0.749; 95% CI, 0.622 to 0.875).

Data from CBC and RET-He can identify patients with IDA, determine need for and responsiveness to intravenous iron, and reduce time for therapeutic decisions. Limitations of this study are uncontrolled design, its single-site and retrospective nature, and that it requires prospective validation.