What is the recommended work‑up and management for iron deficiency in a critically ill patient, including appropriate laboratory tests and intravenous iron therapy?

Assessing for Iron Deficiency in Critically Ill Patients

In critically ill patients with anemia, perform a comprehensive iron panel including plasma iron, transferrin, transferrin saturation, ferritin, CRP, and hepcidin, with reticulocyte hemoglobin content (RET-He) providing the most accurate assessment of functional iron deficiency, and reserve intravenous iron therapy (1 g ferric carboxymaltose) exclusively for patients with confirmed iron deficiency by low hepcidin levels. 1

Diagnostic Work-Up

Initial Laboratory Assessment

Obtain a complete iron panel that must include: 1

• Plasma iron
• Transferrin and transferrin saturation (TSAT)
• Serum ferritin
• C-reactive protein (CRP)
• Hepcidin levels (when available)
• Red blood cell morphology evaluation

Interpretation Challenges in Critical Illness

Traditional iron markers are unreliable in critically ill patients due to inflammation: 1

• Ferritin acts as an acute-phase reactant and increases with inflammation, making levels >300 ng/mL difficult to interpret 1, 2
• Serum iron and transferrin saturation are suppressed by inflammatory cytokines regardless of true iron stores 3
• A ferritin <100 μg/L with TSAT <20% suggests true iron deficiency in the critical care setting 1

Superior Diagnostic Markers

Reticulocyte hemoglobin parameters provide more accurate assessment: 4

• RET-He (reticulocyte hemoglobin content) <29 pg indicates iron-restricted erythropoiesis with superior sensitivity (AUC 0.847) compared to ferritin (AUC 0.678) 1, 4
• Delta-He (Delta-hemoglobin equivalent) shows AUC 0.807 for detecting iron deficiency anemia 4
• Percentage of hypochromic reticulocytes >10% supports functional iron deficiency 1

Hepcidin is the definitive marker when available: 1

• Low hepcidin levels confirm true iron deficiency despite elevated ferritin from inflammation 1
• Elevated hepcidin indicates anemia of inflammation where iron supplementation may be harmful 1

Management Approach

When to Avoid Iron Therapy

The SFAR/SRLF guidelines strongly recommend avoiding iron therapy in most critically ill patients: 1

• Iron should be avoided except when used in conjunction with erythropoietin therapy 1
• This recommendation reflects concerns about iron fueling bacterial growth and worsening inflammation in septic patients 3, 5

Specific Indication for IV Iron

Administer IV iron only when: 1

• Anemia is present in a critically ill patient
• Iron deficiency is confirmed by low hepcidin levels (not just low ferritin or TSAT)
• The patient has demonstrated mortality benefit in this specific context 1

IV Iron Protocol When Indicated

Dosing regimen: 1, 6

• Administer 1 g elemental iron as a single dose 1
• Use ferric carboxymaltose infused over 15 minutes 1, 6
• Alternative formulations include iron sucrose or low molecular weight iron dextran 1, 6

Administration details per FDA labeling: 6

• For patients ≥50 kg: 750 mg IV in two doses separated by at least 7 days, OR 15 mg/kg up to 1,000 mg as single dose
• Dilute up to 1,000 mg in no more than 250 mL sterile 0.9% sodium chloride (concentration ≥2 mg iron/mL)
• Monitor for extravasation as brown discoloration may be long-lasting 6

Monitoring Response

Reassess laboratory parameters 8-10 weeks after IV iron administration: 1

• Do not check ferritin earlier as levels remain falsely elevated immediately post-infusion 1
• Repeat hemoglobin, ferritin, transferrin saturation, and RET-He 1
• Expect hemoglobin increase of 1-2 g/dL and ferritin >100 ng/mL if treatment successful 7

Critical Pitfalls to Avoid

Do not rely on ferritin alone in critically ill patients: 3, 2

• 88% of ICU patients have elevated CRP, which falsely elevates ferritin 3
• Ferritin correlates with severity of illness (SAPS score) and length of ICU stay, not iron stores 2

Do not administer iron based solely on anemia: 1

• 76% of ICU patients are anemic, but most have anemia of inflammation, not iron deficiency 3
• Iron therapy without confirmed deficiency (via hepcidin) may worsen outcomes 1

Recognize functional iron deficiency: 3

• 21% of ICU patients with anemia of inflammation have coexisting true iron deficiency (TSAT <20%, ferritin <100, elevated sTfR) 3
• Hepcidin-mediated iron sequestration creates "functional" deficiency where total body iron is adequate but unavailable for erythropoiesis 1, 3

Check serum phosphate before repeat dosing: 6

• Patients requiring repeat courses within 3 months need phosphate monitoring 6
• Treat hypophosphatemia as medically indicated before additional iron 6