The Role of Reticulocyte-Derived Parameters in the Detection of Iron-Restricted Erythropoiesis in the Elderly

Background: Mindray BC-6800 Plus ^TM (Mindray, Shenzhen, China) measures reticulocyte counts and provides the reticulocyte hemoglobin (RHe, reticulocyte Hb expression) and mean reticulocyte volume (MRV). We studied the performance of those reticulocyte-derived parameters for the detection of iron-restricted erythropoiesis in older patients, compared with standard laboratory tests. Methods: A total of 220 anemic patients, age > 65 years, were recruited in the context of routine health controls. Group differences were assessed using analysis of variance (ANOVA), with p values < 0.05 considered statistically significant. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance of RHe and MRV for detecting iron-restricted erythropoiesis. The reference standard for iron deficiency was sTfR > 52 nmol/L. A multivariable logistic regression model was constructed for iron-restricted erythropoiesis, including MRV, Ret-He and s-ferritin as independent covariates, and adjusted for inflammatory status and renal function. Results: Overall, 30.1% in the group had IDA and 29.0% had mixed IDA/ACD, so 59.1% had absolute or functional iron deficiency, while 40.9% had adequate iron supply. RHe and MRV values differed significantly between both groups (p = 0.0001). For s-ferritin, ROC analysis yielded an AUC of 0.685 (95% CI 0.606-0.767), with the best Youden index at a cut-off of 100 µg/L, corresponding to 72.5% sensitivity and 65.9% specificity. An MRV cut-off of 97.4 fL identified iron-restricted erythropoiesis with 88.2% sensitivity and 82.7% specificity (AUC 0.878, 95% CI 0.799-0.957); RHe AUC 0.860, 95% CI 0.777-0.947; cut-off 30.4 pg; sensitivity 82.4%, specificity 79.8%). In multivariable logistic regression adjusted for CRP and eGFR, s-ferritin was not an independent predictor of iron-restricted erythropoiesis, whereas MRV and RHe remained significant. The overall model demonstrated good discrimination, with an AUC 0.808 (95% CI 0.804-0.814). Conclusions: RHe and MRV are reliable parameters for assessing iron supply to erythropoiesis in older patients and can assist in distinguishing iron-restricted erythropoiesis in complex, inflammation-driven settings.