SCD may be associated with iron overload that occurs following repeated red blood cell (RBC) transfusions. However, in patients with beta thalassemia major, iron overload occurs due to both repeated RBC transfusions and hyperabsorption of iron. The hyperabsorption of iron in beta thalassemia occurs due to ineffective erythropoiesis and subsequent downregulation of hepcidin. Thalassemia intermedia and major are the most studied human models of hepcidin modulation by ineffective erythropoiesis alone and the combined and opposite effect of both ineffective erythropoiesis and transfusion dependent iron overload, accordingly. Regular transfusions induce massive iron loading but inhibit erythropoietic drive. Accordingly, hepcidin production is higher in thalassemia major than in thalassemia intermedia although still inappropriate to the massive transfusional iron loading that partially counteracts the erythropoietic-dependent hepcidin down-regulation (Origa R et al, 2007; Kattamis A et al, 2006; Camberlein E et al, 2008). No differences in the steady-state levels of hepcidin was observed when HbSS patients (N = 40) were compared with healthy hemoglobin AA (HbAA)controls (N = 30) (85.3 ± 30 l μg/L vs. 83.5 ± 40 l μg/L) (Ezeh C et al, 2005).