Diagnostic Utility of Complete Blood Count Indices in Ferritin-Defined Microcytosis Among United States Women Aged 18-49 Years.

INTRODUCTION: Complete blood count (CBC) discrimination indices are widely used as low-cost triage tools for microcytosis, but their diagnostic utility in population-based samples with ferritin-defined iron status is uncertain. We evaluated whether commonly used indices distinguish ferritin-defined iron-deficient from noniron-deficient microcytosis among women aged 18-49 years. METHODS: We analyzed the National Health and Nutrition Examination Survey (NHANES) 2015-2016, 2017-2018, and August 2021-August 2023 data among nonpregnant women aged 18-49 years with CBC, serum ferritin, and survey design variables. Among microcytic (MCV < 80 fL) women, iron-deficient microcytosis was defined as ferritin < 15 ng/mL and noniron-deficient microcytosis as ferritin ≥ 15 ng/mL. Mentzer, England-Fraser, Srivastava, and red cell distribution width (RDW) indices were evaluated at conventional cutoffs. Sensitivity analyses used ferritin < 30 ng/mL and C-reactive protein (CRP) restrictions of ≤ 5 and ≤ 3 mg/L. All estimates were survey-weighted. RESULTS: Among 3991 women, 507 had microcytosis. Ferritin-defined noniron-deficient microcytosis comprised 40.8% (95% CI, 35.5-46.2) and remained 37.0% and 33.6% after CRP restrictions of ≤ 5 and ≤ 3 mg/L. With ferritin ≥ 30 ng/mL, the corresponding proportions were 26.5%, 22.6%, and 20.2%. All four indices showed high sensitivity (92.9%-97.6%) but poor specificity (6.7%-35.3%). RDW had the highest specificity but still misclassified most noniron-deficient cases. CONCLUSIONS: Classic CBC indices had limited utility as standalone triage tools for ferritin-defined microcytosis. Ferritin-based assessment, interpreted in the relevant clinical and inflammatory context, should remain central. Persistent microcytosis without evidence of reduced iron stores should prompt diagnostic reconsideration and, when appropriate, hemoglobinopathy-aware evaluation.