The onset of clinical manifestations in thalassemia major may be insidious and not recognized until late infancy or early toddlerhood (Box 35-5). The clinical effects to thalassemia major are primarily attributable to (1) defective synthesis of HgbA, (2) strucrually impaired RBC, (3) the shortened life span of the erythrocyte. The major consequences of thalassemia are caused by the pathologic condition, resulrant chronic hypoxia, and iron overload from the supportive treatment of multiple blood supplements (Fig.35-5 and Box 35-5)