What is the recommended approach to managing iron status in a patient with ferritin level of 44, transferrin percent saturation of 12.5, and normal hemoglobin level, in the presence of systemic inflammation?

Iron Deficiency in the Setting of Systemic Inflammation

This 15-year-old male has functional iron deficiency despite normal hemoglobin, and given the presence of systemic inflammation, intravenous iron should be considered as first-line treatment rather than oral supplementation.

Diagnostic Interpretation

The laboratory values reveal true iron deficiency masked by inflammation:

• Transferrin saturation of 12.5% is significantly below the normal threshold of 20%, indicating inadequate iron availability for erythropoiesis 1
• Ferritin of 44 µg/L in the presence of inflammation likely represents iron deficiency, as ferritin levels up to 100 µg/L may still reflect iron deficiency when systemic inflammation is present 1
• The hemoglobin of 13.7 g/dL is currently normal but does not exclude iron deficiency, as iron stores are depleted before anemia develops 1

The combination of low transferrin saturation (<20%) with ferritin between 30-100 µg/L in an inflammatory state indicates either true iron deficiency or a mixed picture of iron deficiency with anemia of chronic disease 1.

Treatment Approach

Primary Recommendation: Intravenous Iron

Intravenous iron should be used as first-line therapy in this patient with active systemic inflammation 1. The rationale includes:

• Systemic inflammation inhibits iron absorption through hepcidin upregulation, making oral iron ineffective in active inflammatory states 1
• Intravenous iron bypasses the hepcidin-mediated block at the enterocyte level, allowing direct delivery to iron stores 1
• The 2023 ESPEN guidelines specifically recommend IV iron as first-line treatment in patients with clinically active inflammation 1

If Oral Iron is Considered

If the inflammation is mild or resolving, oral iron may be attempted with strict limitations:

• Maximum dose of 100 mg elemental iron daily in patients without active disease 1
• Alternate-day dosing may improve absorption and reduce side effects compared to daily divided doses 1
• Oral iron should be avoided entirely if inflammation markers (CRP, ESR) indicate active disease 1

Additional Diagnostic Considerations

Before initiating treatment, evaluate for:

• Other causes of anemia: Check vitamin B12 and folate levels, as these deficiencies commonly coexist 1
• Underlying inflammatory condition: Identify and treat the source of systemic inflammation, as this is the primary therapeutic target 1
• Occult blood loss: Consider gastrointestinal evaluation if indicated by history or if iron deficiency persists despite treatment 1
• Advanced markers if available: Hepcidin levels or soluble transferrin receptor can provide additional diagnostic clarity in inflammatory states 1

Monitoring Strategy

After initiating iron therapy:

• Recheck hemoglobin, ferritin, and transferrin saturation after 8-10 weeks, not earlier, as ferritin levels are falsely elevated immediately after IV iron administration 1
• Target ferritin >100 µg/L and transferrin saturation >20% to ensure adequate iron repletion 1
• If inflammation persists, monitor iron parameters every 3 months; if in remission, every 6-12 months 1

Critical Pitfall to Avoid

Do not withhold iron supplementation based solely on "normal" ferritin levels in the presence of inflammation 1. The ferritin of 44 µg/L appears borderline normal but is inappropriately low given the inflammatory state, and the transferrin saturation of 12.5% definitively confirms functional iron deficiency requiring treatment 1.