At what ferritin level is intravenous iron supplementation recommended?

Intravenous Iron Supplementation: Ferritin Thresholds

Intravenous iron supplementation should be considered when ferritin is below 100 ng/mL in the absence of inflammation, with a goal ferritin of 50 ng/mL, though treatment decisions must also incorporate transferrin saturation (TSAT) <20% as a key diagnostic criterion. 1

Diagnostic Thresholds for IV Iron Initiation

General Population (Without Inflammation)

• Ferritin <100 ng/mL has low sensitivity (35-48%) for diagnosing iron deficiency, making it an unreliable sole criterion 1
• TSAT <20% has high sensitivity for diagnosing absolute or functional iron deficiency and should be the primary trigger 1
• Goal ferritin after treatment is 50 ng/mL regardless of sex 1

Patients with Inflammatory Conditions

• Ferritin can be spuriously elevated due to acute phase reactivity, making interpretation challenging 1
• When ferritin is elevated but TSAT <20%, this indicates functional iron deficiency requiring IV iron 1
• Consider soluble transferrin receptor (sTfR) or reticulocyte hemoglobin content (CHr/RET-He) for more accurate assessment when inflammation is present 1

Special Population Considerations

Hemodialysis Patients (CKD)

• Historical guidelines redefined iron deficiency as ferritin <100 μg/L (previously 50 μg/L) 1
• Target ferritin range: >250 and <500 μg/L for maintenance 1
• Upper safety limit: ferritin should not exceed 500-800 μg/L to avoid iron overload toxicity 1
• KDIGO 2012 set upper ferritin limit at 500 μg/L for hemodialysis patients 1

Genetic Iron Disorders (IRIDA)

• IV iron indicated when patients have low TSAT and normal or reduced ferritin who fail oral iron 1
• During treatment, ferritin should preferably not exceed 500 mg/L to avoid toxicity, especially in children and adolescents 1

Clinical Decision Algorithm

1. Measure both ferritin AND TSAT - never rely on ferritin alone 1

2. Without inflammation:

   • Ferritin <50 ng/mL + TSAT <20% → Strong indication for IV iron 1
   • Ferritin 50-100 ng/mL + TSAT <20% → Consider IV iron 1

3. With inflammation:

   • Elevated ferritin + TSAT <20% → Functional iron deficiency, consider IV iron 1
   • Consider sTfR or reticulocyte hemoglobin testing for confirmation 1

4. Severe iron deficiency (ferritin ~7 ng/mL):

   • Requires prompt IV iron repletion 2
   • Target ferritin >100 ng/mL after treatment 2

Dosing and Safety Considerations

• Total iron deficit typically ranges 1392-1531 mg in iron deficiency anemia patients 3
• A cumulative dose of 1500 mg is closer to actual deficit than the commonly used 1000 mg 3
• Avoid IV iron when TSAT >50% or ferritin >800 μg/L as upper safety limits 2
• Do not administer IV iron during active infection 2

Monitoring Post-Treatment

• Reassess iron parameters (CBC, ferritin, TSAT) 4-8 weeks after last infusion 1
• Do not check iron parameters within 4 weeks of total dose infusion due to assay interference 1
• Hemoglobin should increase 1-2 g/dL within 4-8 weeks of therapy 1

Critical Pitfall

The most common error is relying solely on ferritin levels without considering TSAT, particularly in inflammatory states where ferritin is an acute phase reactant and can be falsely elevated despite true iron deficiency 1. Always measure both parameters together.