What is the ferritin threshold to diagnose iron deficiency anemia?

Ferritin Threshold to Diagnose Iron Deficiency Anemia

Use a ferritin cutoff of <45 ng/mL to diagnose iron deficiency in patients with anemia, as this provides the optimal balance between sensitivity and specificity in clinical practice. 1

Diagnostic Thresholds Based on Clinical Context

Standard Threshold (No Inflammation)

• Ferritin <45 ng/mL is the recommended diagnostic cutoff for iron deficiency anemia in patients without inflammatory conditions, with strong evidence supporting this threshold over the traditional <15 ng/mL cutoff 1
• Ferritin <15 ng/mL has 99% specificity for absolute iron deficiency but misses many cases due to low sensitivity 1, 2
• Ferritin <30 ng/mL generally indicates depleted iron stores and is the threshold recommended by European guidelines for patients without active inflammation 1, 2

Adjusted Thresholds for Inflammatory Conditions

• In patients with inflammation, chronic kidney disease, heart failure, IBD, or cancer, use ferritin <100 ng/mL as the diagnostic threshold 2, 3, 4
• Ferritin is an acute-phase reactant that rises during inflammation, potentially masking true iron deficiency even when levels appear "normal" 1, 2
• When ferritin is 30-100 ng/mL in the presence of elevated CRP or ESR, suspect a combination of true iron deficiency and anemia of chronic disease 2

Complementary Testing Required

Always measure transferrin saturation (TSAT) alongside ferritin to improve diagnostic accuracy 2, 3:

• TSAT <20% confirms iron deficiency, particularly when ferritin is in the equivocal range (30-100 ng/mL) 2, 3
• The combination of ferritin <100 ng/mL AND TSAT <20% defines absolute iron deficiency in CKD patients 2
• Calculate TSAT using: (serum iron × 100) ÷ total iron-binding capacity 2

Diagnostic Algorithm

Step 1: Measure ferritin and calculate TSAT

• If ferritin <15 ng/mL → absolute iron deficiency confirmed, proceed to investigate source of blood loss 1, 2
• If ferritin 15-45 ng/mL → iron deficiency highly likely, initiate treatment and investigation 1
• If ferritin 45-100 ng/mL → check inflammatory markers (CRP, ESR) 2

Step 2: Interpret based on inflammation status

• If CRP/ESR normal and ferritin 45-100 ng/mL → likely adequate iron stores, consider alternative causes of anemia 2
• If CRP/ESR elevated and ferritin 45-100 ng/mL with TSAT <20% → mixed picture of iron deficiency and anemia of chronic disease, treat both 2
• If ferritin >100 ng/mL with elevated CRP/ESR → anemia of chronic disease predominates unless TSAT <20%, which suggests functional iron deficiency 2

Critical Caveats

Common pitfall: Using the traditional ferritin cutoff of <15 ng/mL misses the majority of iron deficiency cases because this threshold has high specificity but poor sensitivity 1

Elderly patients: The conventional cutoffs may be inadequate; iron deficiency anemia can develop with ferritin levels up to 100 ng/mL in older adults due to chronic inflammatory conditions 5

Ferritin >150 ng/mL: This level is unlikely to represent absolute iron deficiency, even in the presence of inflammation, and should prompt consideration of alternative diagnoses 1

Special Populations

Premenopausal Women

• Heavy menstrual bleeding is the most common cause 3, 4
• GI investigation is conditional rather than mandatory if menstrual blood loss is the obvious cause 2
• Reserve endoscopy for: age >50, GI symptoms, failure to respond to iron supplementation after 8-10 weeks, or positive H. pylori/celiac testing 2

Chronic Kidney Disease

• Use ferritin <100 ng/mL AND TSAT <20% to define absolute iron deficiency 2
• Functional iron deficiency occurs when ferritin is 100-700 ng/mL but TSAT remains <20% 2

Inflammatory Bowel Disease

• Use ferritin <30 ng/mL in remission or <100 ng/mL in active disease 2
• Monitor every 3 months in active disease, every 6-12 months in remission 2