Re-evaluating ferritin thresholds to diagnose iron deficiency

Iron deficiency (ID) and iron deficiency anemia (IDA) are prevalent and treatable conditions which disproportionately affect women. Serum ferritin is the most sensitive biomarker for ID and IDA, but its utility in clinical decision making is limited by sex-specific reference intervals (RIs) that are frequently lower than evidence-based recommendations. The inclusion of asymptomatic, iron-depleted individuals in RI studies likely accounts for inappropriate ferritin thresholds, and a lower cutoff of 30 µg/L has been proposed by an expert consensus panel to improve sensitivity.In this study, we assessed ferritin RIs for diagnosing ID and IDA in our patient population.

Patient data, including age, sex assigned at birth, hemoglobin, and iron markers, were extracted from the laboratory information system (LIS). Patients were stratified into iron replete (IR), ID, or IDA groups based on measurements for iron, transferrin saturation, and hemoglobin. Ferritin values from the IR group were used to generate new reference ranges and receiver operator characteristic (ROC) curves were plotted to define optimal ferritin cutoffs for diagnosis of ID and IDA.

Ferritin RIs generated from the IR group had lower limit cutoffs of 16.9 µg/L and 30 µg/L for females and males, respectively. Youden Index analysis of ROC curves identified optimal cutoffs of 45 µg/L and 70 µg/L for ID in females and males, respectively, improving diagnostic sensitivity by 44 % in the female group.

These findings are consistent with recommendations for increasing ferritin cutoffs and demonstrate the need for clinical laboratories to re-examine ferritin RIs, particularly for ID diagnosis in the female patient population.