Efficiency of erythropoiesis and effect of transfusion in β-thalassemia. (A) Severity of disease depends on both the degree of anemia and the systemic energy expenditure for erythropoiesis. For example, persons for whom the production of 6 g of hemoglobin (Hb) requires expansion of extramedullary erythropoiesis (EMH) in the liver and spleen, resulting in splenomegaly and changes in bone architecture, and the systemic cost of erythropoiesis is high. Although such a person would probably have his or her disease classified as TI, the initiation of chronic transfusion may improve the quality of life in such cases. (B) Transfusion has a significant number of benefits in β-thalassemia, although the consequent iron overload and potential for alloimmunization are debilitating complications.