A patient with serum iron 27 µg/dL, unsaturated iron‑binding capacity 98 µg/dL, total iron‑binding capacity 125 µg/dL, transferrin saturation 21 %, ferritin 552 ng/mL, normal renal function, and currently taking oral ferrous sulfate, what is the appropriate next step in management?

Management of Functional Iron Deficiency with Elevated Ferritin

Discontinue oral ferrous sulfate immediately and initiate intravenous iron therapy, as this patient has functional iron deficiency (anemia of chronic disease) where hepcidin-mediated blockade prevents intestinal iron absorption despite adequate or elevated iron stores. 1

Diagnostic Interpretation

This patient's iron panel reveals a classic pattern of functional iron deficiency in the setting of chronic inflammation:

• Transferrin saturation of 21% is borderline but combined with other parameters suggests iron-deficient erythropoiesis, as TSAT <20% in inflammatory conditions defines functional iron deficiency 1
• Ferritin 552 ng/mL is markedly elevated, indicating both inflammation (ferritin is an acute-phase reactant) and sequestered iron stores that cannot be mobilized for erythropoiesis 2
• Low serum iron (27 µg/dL) with low TIBC (125 µg/dL) confirms chronic inflammation suppressing transferrin synthesis, distinguishing this from absolute iron deficiency where TIBC would be elevated 1
• The combination of TSAT near 20% with ferritin 100-300+ ng/mL specifically defines functional iron deficiency in chronic disease states, where hepcidin traps iron in storage sites making it unavailable for red blood cell production 1

Key Diagnostic Pitfall

The elevated ferritin of 552 ng/mL might falsely suggest iron overload, but ferritin levels up to 100-300 ng/mL (and sometimes higher) may still indicate true iron deficiency in inflammatory conditions because ferritin reflects both iron stores and inflammation 1. The low TIBC and borderline-low TSAT reveal that stored iron is sequestered and unavailable. 1

Underlying Cause Investigation

Mandatory evaluation includes:

• Inflammatory markers (CRP, ESR) to confirm and quantify the inflammatory state 1
• Complete blood count to assess hemoglobin, MCV, and reticulocyte count 1
• Renal function (creatinine, eGFR) as chronic kidney disease is a common cause of functional iron deficiency and anemia prevalence increases dramatically when GFR <30 mL/min/1.73m² 1
• Gastrointestinal evaluation (endoscopy/colonoscopy) is mandatory in men and postmenopausal women to exclude malignancy as a source of chronic blood loss 1
• Screen for chronic inflammatory conditions: chronic kidney disease, heart failure (iron deficiency prevalence 37-61%), inflammatory bowel disease (13-90%), and malignancy (18-82%) 3

Treatment Algorithm

Step 1: Discontinue Oral Iron

Oral ferrous sulfate is ineffective and should be stopped because:

• In inflammatory states, hepcidin activation blocks intestinal iron absorption while simultaneously trapping iron in storage sites 1
• Oral iron absorption is inversely correlated with body iron stores; when ferritin exceeds approximately 200 ng/mL, additional oral iron will not be absorbed 2
• Even 200 mg elemental iron daily cannot overcome hepcidin-mediated blockade in functional iron deficiency 2

Step 2: Initiate Intravenous Iron

Intravenous iron is the preferred route because it bypasses hepcidin-mediated blockade of intestinal absorption and directly delivers iron to bone marrow 1

Specific IV iron formulations:

• Ferric carboxymaltose, iron sucrose, or low-molecular-weight iron dextran 1
• Typical dosing: 50-125 mg weekly for 8-10 doses, or single 1-g dose of ferric carboxymaltose over 15 minutes 1

Target parameters after IV iron repletion:

• TSAT ≥20% to ensure adequate iron availability for erythropoiesis 1
• Ferritin ≥100 ng/mL in inflammatory conditions (higher threshold than the 30-45 ng/mL target in non-inflammatory states) 1

Step 3: Monitoring Response

• Do NOT recheck iron parameters within 4 weeks of IV iron infusion because circulating iron interferes with assay accuracy and ferritin may be falsely elevated 1
• Optimal timing for reassessment is 4-8 weeks after the last IV iron dose 1
• Expected response: Hemoglobin should increase by 1-2 g/dL within 4-8 weeks; reticulocytosis occurs at 3-5 days after ferric carboxymaltose 1

Step 4: Consider Erythropoiesis-Stimulating Agents (ESAs)

If no response to IV iron occurs after 8 weeks:

• Consider ESAs with continued iron supplementation, particularly if chronic kidney disease or heart failure is present 1
• ESAs require iron supplementation throughout therapy to optimize dose-response and red blood cell production 1
• Maintaining TSAT >20% during ESA therapy is essential to ensure sufficient iron availability 2, 1
• IV iron combined with ESAs yields higher hemoglobin response rates (≈73%) compared with oral iron (≈45%) 1

Common Clinical Pitfalls

• Misinterpreting elevated ferritin as iron overload when it actually reflects inflammation with sequestered, unavailable iron 2
• Continuing oral iron in functional iron deficiency wastes time and exposes patients to gastrointestinal side effects without benefit 2
• Measuring iron parameters too early after IV iron (within 4 weeks) yields falsely elevated results 1
• Failing to investigate underlying chronic inflammatory conditions that require specific management beyond iron repletion 1
• Not recognizing that TSAT is more reliable than ferritin in inflammatory states because it is less affected by inflammation 1

Coordination of Care

Coordinate with nephrology and cardiology for management decisions regarding ESA therapy and treatment of underlying chronic conditions 1