Clinical meaning
Iron deficiency anemia (IDA) is the most common nutritional deficiency worldwide and the most frequent cause of microcytic hypochromic anemia. Iron is essential for hemoglobin synthesis in erythroid precursors; each hemoglobin molecule contains four heme groups, each requiring one iron atom to bind oxygen. Total body iron is approximately 3-4 grams, with 65-70% in hemoglobin, 10% in myoglobin and enzymes, and 20-25% stored as ferritin and hemosiderin in the liver, spleen, and bone marrow. Iron homeostasis is regulated primarily by hepcidin, a hepatic peptide hormone that controls iron absorption from enterocytes and iron release from macrophages by binding to and degrading ferroportin. When iron stores are depleted, hepcidin decreases, allowing increased intestinal iron absorption and macrophage iron release. IDA develops through three progressive stages: (1) iron depletion — ferritin falls below 30 ng/mL while hemoglobin remains normal; (2) iron-deficient erythropoiesis — transferrin saturation falls below 20%, TIBC rises, and free erythrocyte protoporphyrin increases; (3) frank IDA — hemoglobin falls, MCV decreases below 80 fL, and peripheral smear shows microcytic hypochromic red blood cells with increased red cell distribution width (RDW). The clinician must distinguish IDA from anemia of chronic disease (ACD), where ferritin is typically normal or elevated due to inflammation-driven hepcidin elevation that traps iron in macrophages. In mixed IDA/ACD, ferritin may be 30-100 ng/mL; a soluble transferrin receptor (sTfR) level or sTfR/log ferritin index helps differentiate. The reticulocyte count and index classify anemia as hypoproliferative (low reticulocyte index <2, indicating production failure) versus hyperproliferative (elevated reticulocyte index >2, indicating destruction or blood loss with appropriate marrow response).