Revising Ferritin Lower Limits: It's Time to Raise the Bar on Iron Deficiency

Ferritin is a key diagnostic marker of iron deficiency (ID), but the interpretative guidance provided to physicians varies significantly. Clear discrepancies exist between clinical guidelines that recommend evidence-based ferritin cutoffs and clinical laboratories that report highly variable ferritin reference intervals (RIs) derived from apparently healthy populations. In this study, clinical laboratories across North America were surveyed to assess the RIs provided with ferritin results. Although clinical guidelines often recommend ferritin cutoffs of 15 or 30 µg/L to identify uncomplicated ID, the survey showed that 18 of 23 responding laboratories reported female RI lower limits well below 15 µg/L. To understand the clinical impact, we analyzed 52 027 unique patient ferritin values over a 5-year period (2013-2017) from a tertiary care hospital. In this population, the 90th percentile ferritin cutoff to identify ID anemia in adults was 24 µg/L in female patients and 25 µg/L in male patients. Distribution of ferritin results in female patients showed that menopausal status had a significant effect on median values, which increased 2- to 3-fold in the postmenopausal state. Furthermore, sorting the data for female patients by physician specialty showed the highest prevalence of low ferritin values in patients seen in obstetrics and gynecology. This study highlights the discrepancy between clinical guidelines and clinical laboratory practice for ferritin reporting and indicates that ferritin RIs, particularly for female patients, are set to an inappropriately low threshold in most clinical laboratories in North America; this level provides good specificity but poor sensitivity when screening for ID.