What is the appropriate management for a patient with low iron and low Total Iron-Binding Capacity (TIBC) and normal ferritin levels?

Management of Low Iron, Low TIBC, and Normal Ferritin

This pattern suggests anemia of chronic disease (ACD) or anemia of inflammation, not iron deficiency, and the primary management should focus on identifying and treating the underlying inflammatory or chronic disease process rather than iron supplementation. 1

Understanding the Laboratory Pattern

The combination of low serum iron, low TIBC, and normal ferritin is characteristic of anemia of chronic disease (ACD), where inflammation disrupts iron metabolism:

• Low serum iron occurs because inflammation triggers hepcidin production, which blocks iron release from stores and reduces intestinal absorption 1
• Low TIBC (or low transferrin) indicates the acute-phase response is suppressing transferrin synthesis, distinguishing this from true iron deficiency where TIBC is typically elevated 1
• Normal ferritin (especially if >100 μg/L) suggests adequate or even increased iron stores, as ferritin rises as an acute-phase reactant during inflammation 1

This pattern contrasts sharply with isolated iron deficiency, which presents with low iron, high TIBC, and low ferritin 1.

Diagnostic Workup

Assess Inflammatory Status

• Measure inflammatory markers (CRP, ESR) to confirm the presence of inflammation or chronic disease 1
• Check for clinical signs of chronic inflammatory conditions: active inflammatory bowel disease, rheumatologic disorders, chronic infections, malignancy, or chronic kidney disease 1

Refine Iron Status Assessment

When ferritin appears normal but inflammation is present, consider:

• Transferrin saturation (TSAT): Calculate as (serum iron/TIBC) × 100. A TSAT <16-20% suggests functional iron deficiency even with normal ferritin 1
• Ferritin interpretation in inflammation: In the presence of elevated CRP/ESR, ferritin <100 μg/L may still indicate iron deficiency, as inflammation artificially elevates ferritin 1
• Soluble transferrin receptor (sTfR) if available: Elevated in true iron deficiency but normal/low in pure ACD, and not affected by inflammation 1
• Reticulocyte hemoglobin content (CHr or RET-He) if available: Directly assesses functional iron availability for erythropoiesis 1

Rule Out Mixed Anemia

Anemia of mixed origin (AMO)—where iron deficiency coexists with chronic disease—is common in inflammatory conditions:

• If ferritin is 30-100 μg/L with TSAT <16% in the setting of inflammation, suspect coexisting iron deficiency 1
• If sTfR is elevated, this supports true iron deficiency despite inflammation 1

Management Strategy

Primary Approach: Treat the Underlying Disease

The first and most critical step is treating the underlying inflammatory or chronic condition causing ACD 1:

• Active inflammatory bowel disease requires disease-modifying therapy
• Chronic infections need antimicrobial treatment
• Malignancy requires oncologic management
• Chronic kidney disease may need erythropoiesis-stimulating agents

Treating inflammation alone often improves hemoglobin without iron supplementation 1.

Iron Supplementation Considerations

Iron supplementation is NOT routinely recommended when ferritin is normal (>100 μg/L) and TSAT is adequate, as this represents functional iron sequestration rather than true deficiency 1:

• Avoid iron supplementation when ferritin >150 μg/L, as this is unlikely to represent iron deficiency even with inflammation 1
• Iron supplementation with normal/high ferritin is potentially harmful and should not be given 1

Consider iron therapy only if:

• TSAT <16-20% AND ferritin <100 μg/L despite inflammation, suggesting coexisting absolute iron deficiency 1
• sTfR is elevated, confirming true iron deficiency 1

Route of Iron Administration (if indicated)

If true iron deficiency is confirmed alongside chronic disease:

• Intravenous iron is preferred over oral iron in inflammatory conditions, as inflammation-induced hepcidin blocks intestinal iron absorption 1
• IV iron formulations (ferric carboxymaltose, iron isomaltoside, ferumoxytol) allow rapid repletion and bypass absorption barriers 1
• Oral iron is often ineffective in ACD due to hepcidin-mediated absorption blockade 1

Monitoring Response

• Recheck CBC and iron parameters 4-8 weeks after any intervention (not sooner, as recent IV iron interferes with assays) 1
• Hemoglobin should increase 1-2 g/dL within 4-8 weeks if iron was truly deficient 1
• Lack of response suggests pure ACD or ongoing inflammation requiring more aggressive treatment of the underlying disease 1

Common Pitfalls

• Do not reflexively supplement iron based solely on low serum iron—this is often sequestered iron in ACD, not deficiency 1
• Do not ignore normal ferritin in inflammatory states—it may mask true deficiency, but ferritin >150 μg/L reliably excludes deficiency 1
• Do not check iron parameters within 4 weeks of IV iron administration—results will be spuriously elevated 1
• Do not overlook the underlying disease—failure to treat the root cause will result in persistent anemia regardless of iron therapy 1