At what serum ferritin level should an adult (or pregnant) patient be referred for intravenous iron infusion?

Ferritin Thresholds for IV Iron Referral

For most adult patients, IV iron infusion should be considered when ferritin is <100 ng/mL in hemodialysis patients or <30 ng/mL in non-dialysis patients, combined with transferrin saturation (TSAT) <20%, particularly when oral iron has failed or is not tolerated. 1

Clinical Context Determines Thresholds

The ferritin threshold for IV iron referral varies substantially based on clinical setting:

Hemodialysis Patients

• Initiate IV iron when ferritin <100 ng/mL and/or TSAT <20% 1
• Administer 100-125 mg IV iron at each hemodialysis session for 8-10 doses 1
• Most hemodialysis patients require regular IV iron to maintain hemoglobin 11-12 g/dL 1
• Withhold IV iron when ferritin >800 ng/mL and/or TSAT >50% to prevent iron overload 1

Non-Dialysis CKD and General Adult Patients

• First-line treatment is oral iron (200 mg elemental iron daily for adults) 1
• Consider IV iron when ferritin <30 ng/mL with documented oral iron failure, intolerance, or malabsorption 2
• IV iron carries 4.3% risk of infusion reactions and should be reserved for appropriate indications 2

Cancer Patients with Anemia

• IV iron can be offered when ferritin is 30-800 ng/mL and TSAT is 20-50%, particularly when combined with erythropoiesis-stimulating agents (ESAs) 1
• Patients with ferritin up to 600 ng/mL and TSAT <20% may benefit from IV iron, representing functional iron deficiency 1
• IV iron monotherapy (without ESA) has limited evidence but may be considered when ferritin <500 ng/mL 1

Pregnant Patients

• Severe iron deficiency (ferritin <15 ng/mL) warrants IV iron consideration when rapid correction is needed 3
• IV iron demonstrates superior efficacy over oral iron for hemoglobin and ferritin improvement 3

Functional Iron Deficiency: A Critical Concept

Functional iron deficiency occurs when TSAT <20% despite ferritin >100 ng/mL, particularly in patients receiving ESAs or with chronic inflammation 1

• This represents inadequate iron availability for erythropoiesis despite adequate storage iron 1
• In cancer patients, IV iron with ferritin up to 800 ng/mL can improve hemoglobin when TSAT is low 1
• Trial IV iron therapy can be diagnostic: lack of erythropoietic response after 8-10 doses suggests inflammatory block rather than true deficiency 4

Absolute Contraindications to IV Iron

Do not administer IV iron when:

• Ferritin >1000 ng/mL without clear functional deficiency 4
• TSAT >50% (indicates iron overload risk) 1
• Active infection or bacteremia 3
• Known hypersensitivity to IV iron preparations 3
• Anemia not due to iron deficiency 3

Special Populations Requiring Different Thresholds

IRIDA (Iron-Refractory Iron Deficiency Anemia)

• Patients with TMPRSS6 mutations have microcytic anemia with low TSAT and low-normal ferritin 1
• These patients require IV iron when oral iron fails, regardless of specific ferritin threshold 1
• Monitor ferritin to keep <500 ng/mL to avoid toxicity, especially in children 1

Ferroportin Disease

• Do NOT use IV iron for microcytic anemia in ferroportin disease 1
• These patients develop anemia during phlebotomy treatment despite elevated ferritin 1

Monitoring After IV Iron Administration

• Recheck ferritin, hemoglobin, and TSAT at 3 months post-infusion 3
• Target ferritin 100-400 ng/mL for sustained iron stores 3
• Reinitiate IV iron when ferritin drops <100 ng/mL or hemoglobin falls below normal 3
• For doses ≥1000 mg, wait 2 weeks before rechecking iron parameters for accuracy 1

Common Pitfalls to Avoid

• Do not rely on ferritin alone: Always assess TSAT and hemoglobin together, as ferritin is an acute phase reactant elevated by inflammation 2, 4
• Do not give IV iron for normal hemoglobin with mildly low ferritin: This lacks evidence and risks iron overload 2
• Do not continue IV iron without erythropoietic response: If no improvement after 8-10 doses, suspect inflammatory block 4
• Do not exceed ferritin 500-800 ng/mL in most patients: Risk of iron overload and oxidative stress increases 1