What is the diagnosis and recommended management for a patient with serum iron 30 µg/dL, ferritin 259 µg/L, transferrin 177 mg/dL, total iron‑binding capacity 253 µg/dL, and transferrin saturation 12%?

Functional Iron Deficiency (Anemia of Chronic Disease)

This patient has functional iron deficiency (anemia of chronic disease), characterized by elevated ferritin (259.4 µg/L) with severely low transferrin saturation (12%), indicating iron sequestration due to an underlying inflammatory process that must be identified and treated. 1, 2

Diagnostic Interpretation

The laboratory pattern reveals:

• Transferrin saturation of 12% is markedly below the 20% threshold, confirming inadequate iron delivery to bone marrow for erythropoiesis despite adequate storage iron 1, 2
• Ferritin 259.4 µg/L is elevated above the 100 µg/L threshold that, when combined with low transferrin saturation, is diagnostic of anemia of chronic disease 1, 2
• Serum iron 30 µg/dL is low, reflecting iron sequestration in reticuloendothelial macrophages due to hepcidin-mediated blockade 1, 2
• TIBC 253 µg/dL is normal-to-low, which is typical in inflammatory states (unlike absolute iron deficiency where TIBC rises compensatorily) 3, 2

This pattern definitively excludes absolute iron deficiency and indicates that iron is trapped in storage sites and cannot be mobilized for red blood cell production. 1, 2

Immediate Diagnostic Work-Up

Measure Inflammatory Markers

• Check CRP and ESR immediately to confirm the presence of an underlying inflammatory process 3, 2
• Elevated inflammatory markers will confirm anemia of chronic disease as the primary diagnosis 2

Search for Underlying Inflammatory Conditions

The most common causes to investigate include:

• Chronic kidney disease: Check serum creatinine, eGFR, and urinalysis (prevalence of iron deficiency 24-85% in CKD) 4
• Congestive heart failure: Assess for symptoms, BNP/NT-proBNP, and echocardiography (prevalence 37-61% in CHF) 1, 4
• Inflammatory bowel disease: Screen for GI symptoms, fecal calprotectin, and consider colonoscopy (prevalence 13-90% in IBD) 2, 4
• Malignancy: Age-appropriate cancer screening, especially GI and hematologic malignancies (prevalence 18-82% in cancer) 4
• Chronic infection: Evaluate for occult infections, autoimmune conditions (rheumatoid arthritis, lupus), or liver disease 1, 2

Management Strategy

Primary Treatment: Address the Underlying Condition

The most effective treatment for anemia of chronic disease is controlling the underlying inflammatory condition—treating active IBD, managing heart failure, controlling infection, or addressing autoimmune disease will improve anemia by reducing hepcidin levels and restoring iron availability. 2

Iron Supplementation Considerations

• Iron supplementation is generally ineffective in pure anemia of chronic disease (ferritin >100 µg/L with low transferrin saturation) because iron is sequestered and cannot be mobilized due to hepcidin-mediated blockade 2
• However, in specific chronic inflammatory conditions (CKD, CHF, IBD), intravenous iron may still improve hemoglobin despite elevated ferritin when transferrin saturation remains <20-25% 1, 4
• For hemodialysis patients with ferritin 500-1200 ng/mL but transferrin saturation <25%, IV iron may improve hemoglobin response 1
• In heart failure patients, the FAIR-HF and CONFIRM-HF trials demonstrated that IV ferric carboxymaltose improved functional capacity and quality of life even with ferritin levels in this range 1

Erythropoiesis-Stimulating Agents (ESAs)

If the patient has chronic kidney disease or heart failure with persistent anemia despite treating the underlying condition:

• Initiate ESAs only when hemoglobin <10 g/dL and after ensuring adequate iron stores 2
• Target hemoglobin should not exceed 11 g/dL, as higher targets significantly increase risks of death, stroke, and cardiovascular events 2
• Ensure supplemental iron (preferably IV) is administered when ferritin <200 µg/L or transferrin saturation <20% in patients receiving ESAs 1, 2

Critical Pitfalls to Avoid

• Do not assume this patient has absolute iron deficiency based on low serum iron alone—ferritin >100 µg/L with low transferrin saturation is the hallmark of functional iron deficiency, not depleted stores 3, 2
• Do not give oral iron supplementation when ferritin >100 µg/L and no chronic inflammatory condition requiring IV iron has been identified, as this risks iron overload without clinical benefit 2
• Do not overlook the underlying inflammatory condition—failure to identify and treat the root cause (CHF, CKD, IBD, malignancy, infection) will result in persistent anemia regardless of iron therapy 1, 2
• If ferritin and transferrin saturation are discordant or the diagnosis remains unclear, consider measuring soluble transferrin receptor (sTfR)—elevated sTfR confirms true iron deficiency even in the presence of inflammation 2, 5, 6

Follow-Up and Monitoring

• Recheck CBC, complete iron panel (iron, ferritin, TIBC, transferrin saturation), and inflammatory markers (CRP, ESR) in 4-8 weeks after initiating treatment of the underlying condition 2
• If hemoglobin does not increase by ≥1 g/dL after 4 weeks of appropriate therapy, reassess for other causes of anemia including vitamin B12/folate deficiency, hemolysis, or bone marrow disease 2
• For patients with chronic inflammatory conditions requiring ongoing management, monitor iron parameters every 3-6 months 1, 2