A patient with serum iron 7.9 µmol/L, total iron‑binding capacity 64.8 µmol/L, transferrin saturation 12 % and ferritin 140 ng/mL—what is the most likely diagnosis and how should it be managed?

Anemia of Chronic Disease with Functional Iron Deficiency

This patient has functional iron deficiency in the setting of chronic inflammation—the low transferrin saturation (12%) confirms iron-deficient erythropoiesis despite the seemingly "normal" ferritin of 140 ng/mL, which is elevated by inflammation and masks true iron depletion. 1

Diagnostic Interpretation

The combination of TSAT <20% with ferritin 100-300 ng/mL specifically defines functional iron deficiency in chronic disease states, where hepcidin activation traps iron in storage sites making it unavailable for hemoglobin synthesis. 1 In this case:

• TSAT of 12% is well below the 16-20% threshold, confirming iron-deficient erythropoiesis regardless of ferritin levels 1
• Ferritin 140 ng/mL appears "normal" but actually indicates inflammation is present and iron stores are sequestered—ferritin up to 100-300 ng/mL may still reflect genuine iron deficiency in inflammatory conditions 1
• Low serum iron (7.9 µmol/L) combined with low TIBC (64.8 µmol/L) indicates chronic inflammation suppressing transferrin synthesis, rather than the elevated TIBC seen in pure iron deficiency 1
• The elevated transferrin (2.58 g/L, assuming this is the unit) with low TIBC is paradoxical and suggests laboratory error or unit confusion—TIBC should equal transferrin × 25.1 1, but this requires verification

Underlying Cause Investigation

Mandatory workup to identify the chronic inflammatory condition driving this picture:

• Chronic kidney disease: Check creatinine, eGFR, and urinalysis—anemia prevalence increases dramatically when GFR <30 mL/min/1.73m² 1
• Chronic heart failure: Assess BNP/NT-proBNP and echocardiography—iron deficiency is highly prevalent in CHF, defined by ferritin <100 μg/L or TSAT <20% 1
• Inflammatory bowel disease: Check CRP, ESR, and consider colonoscopy if GI symptoms present 1
• Malignancy screening: Age-appropriate cancer screening is mandatory, especially GI evaluation in men and postmenopausal women to exclude malignancy as a source of chronic blood loss 1
• Inflammatory markers: Measure CRP and ESR to confirm inflammatory state 1
• Complete blood count: Assess hemoglobin level and MCV to determine severity of anemia 1

Management Algorithm

Step 1: Initiate Intravenous Iron Therapy

• IV iron is first-line therapy because it bypasses hepcidin-mediated blockade of intestinal iron absorption that occurs in inflammatory states, directly delivering iron to bone marrow 1
• Preferred formulations: Ferric carboxymaltose, iron sucrose, or low-molecular-weight iron dextran 1
• Dosing: Weekly IV iron 50-125 mg for 8-10 doses 1
• Oral iron is ineffective in functional iron deficiency due to hepcidin blockade of intestinal absorption 1

Step 2: Target TSAT ≥20% After Iron Repletion

• Goal TSAT ≥20% ensures adequate iron availability for erythropoiesis 1
• In chronic inflammatory conditions, target ferritin ≥100 ng/mL together with TSAT ≥20% to ensure true iron repletion despite inflammation-induced ferritin elevation 1

Step 3: Monitor Response

• Do not measure iron parameters within 4 weeks of IV iron infusion—circulating iron interferes with the assay 1
• Optimal window for re-evaluation is 4-8 weeks after the last infusion 1
• Adequate iron therapy should raise hemoglobin by 1-2 g/dL within 4-8 weeks of treatment initiation 1
• Reticulocytosis occurs at 3-5 days after ferric carboxymaltose, indicating bone marrow response 1

Step 4: Consider Erythropoiesis-Stimulating Agents (ESAs)

• If no response to IV iron occurs, 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
• When ESAs are used with iron, IV iron yields higher hemoglobin response rate (≈73%) compared with oral iron (≈45%) 1

Common Pitfalls to Avoid

• Relying solely on ferritin without checking TSAT leads to missed diagnoses—ferritin is an acute-phase reactant and can be elevated in inflammation, necroinflammatory liver disease, lymphomas, and chronic inflammatory conditions 2, 1
• Assuming ferritin 140 ng/mL means "adequate iron stores"—in inflammatory states, ferritin up to 100-300 ng/mL may still indicate true iron deficiency 1
• Prescribing oral iron in functional iron deficiency is futile—hepcidin blocks intestinal absorption, making IV iron mandatory 1
• Not recognizing that functional iron deficiency can occur despite normal or elevated ferritin levels is a common pitfall 1
• Failing to investigate the underlying chronic inflammatory condition—this is not just "iron deficiency" but a manifestation of serious underlying disease requiring diagnosis 1