Iron-Deficiency Anemia.

Iron deficiency and iron-deficiency anemia are global health problems and common medical conditions seen in everyday clinical practice. Although the prevalence of iron-deficiency anemia has recently declined somewhat, iron deficiency continues to be the top-ranking cause of anemia worldwide, and iron-deficiency anemia has a substantial effect on the lives of young children and premenopausal women in both low-income and developed countries.1 The diagnosis and treatment of this condition could clearly be improved. Iron is crucial to biologic functions, including respiration, energy production, DNA synthesis, and cell proliferation.2 The human body has evolved to conserve iron in several ways, including the recycling of iron after the breakdown of red cells and the retention of iron in the absence of an excretion mechanism. However, since excess levels of iron can be toxic, its absorption is limited to 1 to 2 mg daily, and most of the iron needed daily (about 25 mg per day) is provided through recycling by macrophages that phagocytose senescent erythrocytes. The latter two mechanisms are controlled by the hormone hepcidin, which maintains total-body iron within normal ranges, avoiding both iron deficiency and excess. Iron deficiency refers to the reduction of iron stores that precedes overt irondeficiency anemia or persists without progression. Iron-deficiency anemia is a more severe condition in which low levels of iron are associated with anemia and the presence of microcytic hypochromic red cells. Iron-restricted erythropoiesis indicates that the delivery of iron to erythroid precursors is impaired, no matter how replete the stores.3,4 Stores may be normal or even increased because of iron sequestration in cases of anemia of chronic inflammation, which is observed in patients with autoimmune disorders, cancer, infections, and chronic kidney diseases.3,4 The presence of both iron deficiency and anemia of chronic disorders is common and may be seen in elderly patients5 and patients with chronic kidney disease.6 However, a substantial fraction of the anemia that is typical in elderly patients occurs in the absence of iron deficiency or elevated hepcidin levels.7 Functional iron deficiency is a state of iron-poor erythropoiesis8 in which there is insufficient mobilization of iron from stores in the presence of increased demands, as is observed after treatment with erythropoiesis-stimulating agents.9 (See the Glossary for definitions of terms related to iron-deficiency anemia.) This review reconsiders iron deficiency and its anemia in light of advances in the understanding of systemic iron homeostasis and examines causes, pathophysiological features, and treatment options in adults. Readers are referred elsewhere for information on the presentation, symptoms, and diagnosis of iron-deficiency anemia through laboratory tests and on issues that are specific to children or pregnancy.10-13 From Vita Salute University and San Raffaele Scientific Institute, Milan. Address reprint requests to Dr. Camaschella at Vita Salute University, San Raffaele Scientific Institute, Via Olgettina, 58, 20132 Milan, Italy, or at camaschella . clara@ hsr . it.