A 60-year-old man with rheumatoid arthritis has hemoglobin 9.8 g/dL, MCV 78 fL, serum iron low, TIBC low, ferritin 180 ng/mL, and soluble transferrin receptor normal. The central mediator responsible for this anemia acts by which mechanism?

• A Suppressing erythropoietin production by the kidney
• B Binding transferrin and preventing iron uptake by marrow
• C Directly inhibiting ALA synthase in erythroid precursors
• D Blocking ferroportin and trapping iron in macrophages ✓

Explanation

Anemia of chronic disease is driven by inflammatory cytokines, especially IL-6, which induce hepatic hepcidin. Hepcidin binds ferroportin on macrophages and enterocytes, causing its internalization and blocking iron export, so iron is sequestered and unavailable for erythropoiesis. Erythropoietin levels are relatively low for the degree of anemia but suppression of renal EPO production is not the primary mechanism, and hepcidin does not act on ALA synthase.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

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