A patient with hemoglobin 8.6 g/dL, serum iron 44 µg/dL, total iron‑binding capacity (TIBC) 228 µg/dL, transferrin saturation 19 % and ferritin 240 ng/mL—what is the most likely diagnosis and next‑step management?

Anemia of Chronic Disease with Functional Iron Deficiency

This patient has functional iron deficiency (anemia of chronic disease with iron-deficient erythropoiesis), and the next step is to investigate the underlying chronic inflammatory condition—particularly gastrointestinal malignancy, chronic kidney disease, or inflammatory bowel disease—followed by intravenous iron therapy.

Diagnostic Interpretation

The laboratory pattern is diagnostic for functional iron deficiency:

• Transferrin saturation of 19% is below the 20% threshold, confirming iron-deficient erythropoiesis regardless of ferritin levels 1
• Ferritin of 240 ng/mL is elevated above 100 ng/mL, indicating inflammation is present and iron stores are sequestered 1
• TIBC of 228 µg/dL is low-normal to slightly reduced, reflecting chronic inflammation suppressing transferrin synthesis 2
• Serum iron of 44 µg/dL is low, confirming inadequate iron availability for hemoglobin production 2

This combination—TSAT <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. The bone marrow lacks sufficient available iron to produce hemoglobin despite seemingly adequate ferritin levels 1.

Mandatory Investigation of Underlying Cause

Gastrointestinal evaluation is mandatory in this patient to exclude malignancy as a source of chronic blood loss 1. The presence of iron deficiency mandates a search for the underlying cause 2.

Evaluate systematically for:

• Gastrointestinal bleeding: Obtain stool guaiac testing; if positive, proceed to endoscopic evaluation (upper and lower) 2
• Chronic kidney disease: Calculate estimated glomerular filtration rate and obtain urinalysis to assess for proteinuria or hematuria 2. CKD is associated with dramatically increased anemia prevalence when GFR <30 mL/min/1.73m² 1
• Inflammatory bowel disease: Consider colonoscopy if GI symptoms are present 1
• Chronic heart failure: Assess for symptoms and obtain echocardiography if indicated 1
• Malignancy: Age-appropriate cancer screening, particularly given the anemia severity 3

Obtain inflammatory markers (C-reactive protein, erythrocyte sedimentation rate) to confirm the inflammatory state 1.

Treatment Algorithm

Step 1: Intravenous Iron is First-Line Therapy

IV iron bypasses hepcidin-mediated blockade of intestinal iron absorption that occurs in inflammatory states, directly delivering iron to bone marrow 1. Oral iron will fail in this setting because inflammation blocks gastrointestinal absorption 1.

Administer:

• Weekly IV iron 50-125 mg for 8-10 doses 1
• Specific formulations include ferric carboxymaltose, iron sucrose, or low-molecular-weight iron dextran 3

Step 2: Target Parameters After Iron Repletion

• TSAT ≥20% to ensure adequate iron availability for erythropoiesis 1
• Ferritin ≥100 ng/mL to confirm sufficient iron stores in the setting of chronic inflammation 2

Step 3: Re-evaluate Iron Parameters

Do not measure iron parameters within 4 weeks of IV iron infusion because circulating iron interferes with the assay 1. The optimal window for re-evaluation is 4-8 weeks after the last infusion 1.

Step 4: Consider Erythropoiesis-Stimulating Agents

If no response to IV iron occurs after 8-9 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. Intravenous iron is superior to oral iron when used with ESAs, producing greater hemoglobin increases (73% response rate vs 45% with oral iron) 3.

Common Pitfalls to Avoid

• Do not rely on ferritin alone: Normal or elevated ferritin does not exclude iron deficiency in inflammatory states 2. Ferritin up to 100-300 ng/mL may still indicate true iron deficiency when inflammation is present 1
• Do not prescribe oral iron: It will fail because hepcidin blocks intestinal absorption in inflammatory conditions 1
• Do not delay investigation: The combination of anemia (Hb 8.6 g/dL) and functional iron deficiency requires urgent evaluation for malignancy, particularly in men and postmenopausal women 1
• Do not misinterpret TSAT: TSAT <20% indicates iron-deficient erythropoiesis regardless of ferritin levels 1. It is more reliable than ferritin in inflammatory states because it is less affected by inflammation 1

Expected Response to Treatment

Reticulocytosis should occur at 3-5 days after IV iron administration, indicating bone marrow response 1. Adequate iron therapy should raise hemoglobin by 1-2 g/dL within 4-8 weeks of treatment initiation 1.