What is the most likely diagnosis and appropriate management for a patient with a transferrin saturation of 7%, serum iron of 23 µg/dL, and ferritin of 109 ng/mL?

Anemia of Chronic Disease with Functional Iron Deficiency

Your patient has functional iron deficiency in the setting of inflammation—the combination of transferrin saturation 7% (far below the 20% threshold), ferritin 109 ng/mL (elevated by inflammation), and serum iron 23 µg/dL (low) defines anemia of chronic disease with iron-deficient erythropoiesis that requires intravenous iron therapy and aggressive treatment of the underlying inflammatory condition. 1, 2

Diagnostic Interpretation

Iron Parameters Analysis

• Transferrin saturation 7% is markedly below the diagnostic threshold of 16–20% and confirms that iron is unavailable for red blood cell production, regardless of ferritin level. 1, 2, 3
• Ferritin 109 ng/mL sits just above the 100 ng/mL cutoff; in the presence of inflammation this value indicates that iron stores are sequestered by hepcidin and cannot be mobilized for erythropoiesis. 1, 2
• Serum iron 23 µg/dL (low) combined with elevated TIBC reflects the body's attempt to capture more circulating iron but inability to access stored iron. 2, 3
• The diagnostic criteria for anemia of chronic disease are met: ferritin >100 µg/L and transferrin saturation <16% in the presence of clinical or biochemical inflammation. 1, 2

Critical Distinction: Functional vs. Absolute Iron Deficiency

• Functional iron deficiency occurs when ferritin is 100–300 ng/mL with TSAT <20% during inflammation; hepcidin traps iron in storage sites (macrophages, hepatocytes) making it unavailable despite adequate total body iron. 1, 2
• If ferritin were 30–100 µg/L with TSAT <20%, this would indicate a mixed picture of true iron deficiency plus anemia of chronic disease. 1, 2
• Your patient's ferritin of 109 ng/mL places them at the borderline between these two categories, but the severely depressed TSAT of 7% confirms iron-deficient erythropoiesis requiring treatment. 1, 2

Mandatory Next Steps

1. Confirm Inflammatory State

• Measure C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) immediately to document active inflammation, which explains the elevated ferritin and guides treatment decisions. 1, 2
• Obtain a complete blood count with MCV, MCH, RDW, and reticulocyte count to assess anemia severity and red-cell morphology. 2

2. Investigate Underlying Causes

• In men and postmenopausal women, gastrointestinal evaluation (upper endoscopy + colonoscopy) is mandatory to exclude occult malignancy as a source of chronic blood loss, even when inflammation is present. 2
• Evaluate for chronic inflammatory conditions: chronic kidney disease (measure creatinine and eGFR), heart failure (BNP/NT-proBNP, echocardiography), inflammatory bowel disease (colonoscopy if GI symptoms), and active infection. 2, 4
• In premenopausal women, assess menstrual blood loss patterns and consider gynecologic evaluation. 2

Treatment Algorithm

Primary Intervention: Intravenous Iron

• Intravenous iron (ferric carboxymaltose, iron sucrose, or low-molecular-weight iron dextran) is the first-line therapy because it bypasses hepcidin-mediated blockade of intestinal iron absorption that renders oral iron ineffective in functional iron deficiency. 1, 2, 5
• A typical regimen is 500 mg IV iron initially, followed by a second 500 mg dose four weeks later. 2
• Do not use oral iron in this setting; when ferritin exceeds 100 ng/mL and inflammation is present, hepcidin prevents intestinal iron uptake and oral supplementation provides no benefit. 2

Concurrent Management of Inflammation

• Aggressive treatment of the underlying inflammatory disease is essential to reduce hepcidin levels and permit mobilization of sequestered iron stores. 1, 2
• Treating inflammation alone is rarely sufficient to normalize hemoglobin; iron repletion must occur simultaneously. 1

Monitoring Response

• Do not recheck iron parameters within 4 weeks of IV iron infusion because circulating iron interferes with assay accuracy and ferritin will be falsely elevated. 2, 3
• The optimal timing for reassessment is 4–8 weeks after the last IV iron dose; measure CBC, ferritin, TSAT, and CRP. 2, 3
• Target TSAT ≥20% after iron repletion to ensure adequate iron availability for erythropoiesis. 2, 3
• Expect hemoglobin to rise by 1–2 g/dL within 4–8 weeks of appropriate therapy. 2

Consideration of Erythropoiesis-Stimulating Agents (ESAs)

• If hemoglobin fails to improve after IV iron and inflammation persists—particularly in chronic kidney disease (eGFR <30 mL/min/1.73 m²) or heart failure (NYHA class II–III)—consider adding an ESA. 2, 5
• ESAs require ongoing iron supplementation; maintain TSAT >20% throughout ESA therapy because erythropoietin-stimulated red-cell production rapidly depletes available iron. 2, 5, 4
• In hemodialysis patients receiving ESAs, targeting TSAT 30–50% reduces ESA dose requirements compared with targeting 20–30%. 2

Common Diagnostic Pitfalls

• Do not interpret ferritin 109 ng/mL as "normal iron stores" in the presence of inflammation; ferritin is an acute-phase reactant and this value may still represent true iron deficiency. 1, 2
• Do not rely on ferritin alone; TSAT is less affected by inflammation and provides a more reliable assessment of iron availability for red-cell production. 2, 3, 6
• Do not prescribe oral iron when functional iron deficiency is present; it will not be absorbed and exposes the patient to unnecessary gastrointestinal side effects. 2
• Do not delay gastrointestinal investigation while awaiting response to iron therapy; malignancy work-up should proceed in parallel, especially in adults over 50 years. 2
• Do not assume menstrual blood loss explains severe iron deficiency in perimenopausal women; gastrointestinal pathology must still be excluded. 2

Special Population Considerations

Inflammatory Bowel Disease

• In IBD patients in remission, ferritin <30 µg/L reliably indicates iron deficiency; during active inflammation, ferritin values up to 100 µg/L may still represent iron deficiency. 1, 2
• IV iron is preferred in active IBD because hepcidin-mediated blockade of intestinal absorption is pronounced. 1, 2

Chronic Kidney Disease

• Absolute iron deficiency in CKD is defined as TSAT ≤20% with ferritin ≤100 ng/mL (predialysis/peritoneal dialysis) or ≤200 ng/mL (hemodialysis). 2, 4
• For non-dialysis CKD patients not receiving ESAs, consider IV iron if TSAT ≤30% and ferritin ≤500 ng/mL to achieve hemoglobin rise without initiating ESA therapy. 2

Chronic Heart Failure

• Iron deficiency in CHF is defined as ferritin <100 ng/mL or ferritin 100–300 ng/mL with TSAT <20%. 2
• IV iron improves functional capacity, quality of life, and NYHA class in iron-deficient CHF patients, irrespective of anemia status. 2