Hepcidin regulation in β-thalassemia major. Hepcidin production is modulated by suppressive effects of erythropoiesis and stimulatory effects of iron overload. (A) Before transfusion, exuberant erythropoietic activity suppresses hepcidin through an as yet poorly defined mechanism. Lower hepcidin would be expected to result in increased dietary iron loading. (B) After transfusion, ineffective erythropoiesis is alleviated, resulting in hepcidin de-repression. The effect of iron loading becomes apparent chronically rather than immediately after transfusion. Hepcidin measurements should help determine how well ineffective erythropoiesis is managed in β-thalassemia patients.