Other than iron deficiency, only three conditions need to be consid- ered in the differential diagnosis of a hypochromic microcytic anemia (Table 93-4). The first is an inherited defect in globin chain synthesis: the thalassemias. These are differentiated from iron deficiency most readily by serum iron values; normal or increased serum iron levels and transferrin saturation are characteristic of the thalassemias. In addition, the red blood cell distribution width (RDW) index is gener- ally normal in thalassemia and elevated in iron deficiency. The second condition is the anemia of inflammation (AI; also referred to as the anemia of chronic disease) with inadequate iron supply to the erythroid marrow. The distinction between true iron- deficiency anemia and AI is among the most common diagnostic prob- lems encountered by clinicians (see below). Usually, AI is normocytic and normochromic. The iron values usually make the differential diag- nosis clear, as the ferritin level is normal or increased and the percent transferrin saturation and TIBC are typically below normal. Finally, the myelodysplastic syndromes represent the third and least common condition. Occasionally, patients with myelodysplasia have impaired hemoglobin synthesis with mitochondrial dysfunction, resulting in impaired iron incorporation into heme. The iron values again reveal normal stores and more than an adequate supply to the marrow, despite the microcytosis and hypochromia. TREATMENT Iron-Deficiency Anemia The severity and cause of iron-deficiency anemia will determine the appropriate approach to treatment. As an example, symptom- atic elderly patients with severe iron-deficiency anemia and car- diovascular instability may require red cell transfusions. Younger individuals who have compensated for their anemia can be treated more conservatively with iron replacement. The foremost issue for the latter patient is the precise identification of the cause of the iron deficiency. For the majority of cases of iron deficiency (pregnant women, growing children and adolescents, patients with infrequent episodes of bleeding, and those with inadequate dietary intake of iron), oral iron therapy will suffice. For patients with unusual blood loss or malabsorption, specific diagnostic tests and appropriate therapy take priority. Once the diagnosis of iron-deficiency anemia and its cause is made, there are three major therapeutic approaches.