What is the best course of action for a patient with anemia, normal MCV, low transferrin saturation, normal ferritin, normal Vitamin B12, and normal folic acid levels, who is currently receiving iron supplementation?

Anemia of Chronic Disease with Functional Iron Deficiency

This patient has anemia of chronic disease (inflammatory anemia) with functional iron deficiency, not true iron deficiency, and should discontinue daily oral iron supplementation immediately. The elevated ferritin (386 ng/mL) combined with low transferrin saturation (27.39%) indicates iron sequestration in storage sites rather than depleted iron stores, making continued oral iron therapy ineffective and potentially harmful 1, 2.

Diagnostic Interpretation

The laboratory pattern confirms functional iron deficiency in the context of inflammation:

• Hemoglobin 8.3 g/dL indicates moderate anemia requiring treatment 1
• Normal MCV (92 fL) suggests this is not classic iron deficiency anemia, which typically presents as microcytic 1, 3
• Low serum iron (45 μg/dL) reflects iron sequestration, not depletion 2
• Low transferrin saturation (27.39%) indicates insufficient iron delivery to bone marrow despite adequate stores 2, 4
• Elevated ferritin (386 ng/mL) rules out absolute iron deficiency and suggests inflammation 1, 2

The European Crohn's and Colitis Organisation defines anemia of chronic disease as ferritin >100 μg/L with transferrin saturation <20% in the presence of inflammation 1. This patient's ferritin of 386 ng/mL far exceeds this threshold, confirming that iron is trapped in storage sites rather than depleted 2.

Why Oral Iron Should Be Discontinued

Continuing oral iron supplementation in this patient is both ineffective and potentially harmful:

• Oral iron cannot overcome the inflammatory block that prevents iron mobilization from stores 1
• Non-absorbed oral iron (>90% of ingested iron) generates reactive oxygen species that can exacerbate underlying inflammatory conditions 1
• The patient has already demonstrated failure to respond to oral iron therapy, as evidenced by persistent anemia despite "daily iron supplementation" 1, 4

The Journal of Crohn's and Colitis specifically warns that oral iron preparations can lead to gastrointestinal adverse effects and potentially worsen inflammatory conditions through the Fenton reaction 1.

Recommended Management Algorithm

Step 1: Identify and treat the underlying inflammatory condition

• Check inflammatory markers (CRP, ESR) to confirm active inflammation 1, 2
• Investigate for chronic inflammatory diseases: inflammatory bowel disease, chronic kidney disease, rheumatologic conditions, chronic infections, or malignancy 1, 2
• Treating the underlying inflammation is the first and most critical step, as this alone may improve anemia 1

Step 2: Consider intravenous iron therapy

If the patient remains symptomatic or hemoglobin fails to improve after addressing inflammation, intravenous iron is the appropriate next step 1. The European evidence-based consensus demonstrates that IV iron is more effective than oral iron in inflammatory conditions, delivers faster response rates, and is safer 1.

Intravenous iron is specifically indicated when 1:

• Patients are intolerant or unresponsive to oral iron (as demonstrated here)
• Chronic inflammation is present
• Rapid correction of anemia is needed

Step 3: Discontinue oral iron immediately

• Stop daily oral iron supplementation 1
• Oral iron has no role when ferritin >100 ng/mL in the context of inflammation 1, 2

Step 4: Monitor response

• Recheck hemoglobin, ferritin, and transferrin saturation in 8-12 weeks 4
• If no improvement occurs, consider erythropoiesis-stimulating agents in specific contexts (e.g., chronic kidney disease) 1

Critical Pitfalls to Avoid

Do not continue oral iron based solely on low transferrin saturation 2, 4. The combination of elevated ferritin with low transferrin saturation indicates functional iron deficiency (iron sequestration), not absolute iron deficiency (depleted stores) 2. Continuing oral iron in this setting provides no benefit and risks harm 1.

Do not assume this is simple iron deficiency anemia 1, 2. The normal MCV and elevated ferritin exclude classic iron deficiency anemia, which presents with microcytic anemia and ferritin <30 ng/mL 1, 2, 3.

Do not delay investigation of the underlying cause 1. Anemia of chronic disease always has an underlying inflammatory etiology that requires identification and treatment 1. The elevated ferritin itself suggests chronic inflammation, malignancy, or chronic disease 2.

Special Considerations

If chronic kidney disease is present, different thresholds apply. The National Kidney Foundation defines absolute iron deficiency in CKD as ferritin <100 ng/mL with transferrin saturation <20% 1. This patient's ferritin of 386 ng/mL exceeds this threshold, confirming functional rather than absolute deficiency even in the CKD context 1.

The KDIGO guideline specifies that ferritin levels up to 500 ng/mL with transferrin saturation ≤30% may warrant IV iron supplementation in CKD patients receiving erythropoiesis-stimulating agents 1, 5. However, the long-term safety of high-dose IV iron at these ferritin levels remains uncertain 5.