What is the diagnosis and treatment for a patient with hypoferritinemia (low iron level), low iron saturation, elevated Total Iron Binding Capacity (TIBC), and elevated transferrin level?

Iron Deficiency Anemia (Functional Iron Deficiency)

This patient has functional iron deficiency (also called iron-deficient erythropoiesis), where iron stores are present but sequestered and unavailable for red blood cell production due to inflammation or chronic disease. 1

Diagnostic Interpretation

The laboratory values confirm this diagnosis through the following pattern:

• Transferrin saturation of 10% is well below the diagnostic threshold of 16-20%, confirming iron-deficient erythropoiesis regardless of what the ferritin level shows 1
• Low serum iron (28) combined with elevated TIBC (293) and elevated transferrin (209) indicates the body is attempting to capture more iron but cannot access stored iron 2
• This specific combination (TSAT <20% with evidence of inflammation) defines functional iron deficiency, where hepcidin activation traps iron in storage sites making it unavailable for hemoglobin synthesis 1

Critical Next Step: Identify the Underlying Cause

You must investigate for chronic inflammatory conditions and sources of blood loss before initiating treatment. 1

Mandatory Evaluations:

• Gastrointestinal evaluation (colonoscopy and upper endoscopy) is mandatory in men and postmenopausal women to exclude malignancy as a source of chronic blood loss 1, 2
• Screen for chronic inflammatory conditions: chronic kidney disease, heart failure, inflammatory bowel disease, autoimmune disorders, and malignancy 1, 2
• Inflammatory markers: Check CRP and ESR to confirm inflammatory state 2
• Complete blood count: Assess hemoglobin level and MCV to determine severity of anemia 2

Common Pitfall to Avoid:

Do not rely solely on ferritin levels in this context—ferritin is an acute phase reactant and will be falsely elevated in inflammation, masking true iron deficiency 2. The transferrin saturation of 10% is the definitive marker here.

Treatment Algorithm

First-Line Treatment: Intravenous Iron

Intravenous iron is the preferred treatment for functional iron deficiency because it bypasses the hepcidin-mediated blockade of intestinal iron absorption that occurs in inflammatory states. 1

• IV iron directly delivers iron to bone marrow, circumventing the GI absorption problem 1
• Oral iron supplementation will be poorly absorbed and ineffective in this inflammatory state 2, 1
• Target TSAT ≥20% after iron repletion to ensure adequate iron availability for erythropoiesis 1

Monitoring Response:

• Reticulocytosis should occur at 3-5 days after IV iron administration, indicating bone marrow response 1
• Recheck CBC and iron parameters (ferritin, TSAT) 4-8 weeks after the last infusion 1
• Do not evaluate iron parameters within 4 weeks of total dose iron infusion as circulating iron interferes with the assay 1

If No Response to IV Iron:

Consider erythropoiesis-stimulating agents (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.

Key Diagnostic Thresholds Summary

• TSAT <16% in healthy individuals = absolute iron deficiency 1
• TSAT <20% in inflammatory conditions = iron-deficient erythropoiesis (functional iron deficiency) 1, 2
• Ferritin 30-100 μg/L with TSAT <20% = combination of true iron deficiency and anemia of chronic disease 2
• Ferritin >100 μg/L with TSAT <20% = functional iron deficiency in chronic disease states 1