Description

Microcytic anemia is defined as a hemoglobin 2 standard deviations (SD) below the mean associated with an abnormally low mean corpuscular volume (MCV). Use of age-based norms for both indices is critical.

Epidemiology

• In pediatrics, the most common cause of microcytic anemia is iron deficiency anemia (IDA).
• IDA incidence by age:
  • 1 to 2 years, 14%
  • Adolescent females, 9%
• Hemoglobinopathies causing microcytic anemia are common in Mediterranean countries, Southeast Asia, China, Africa, and India. Incidence in the United States is currently increasing due to increasing immigration.

Risk Factors

• Prematurity, breastfeeding, lower socioeconomic class, and overweight infants are more likely to have IDA.
• Certain ethnic groups such as African Americans and Hispanics have higher rates of iron deficiency. These groups also have a higher incidence of hemoglobinopathies, which can complicate the clinical picture.
• Exposures to lead-based products can cause microcytic anemia resulting from lead poisoning.

Pathophysiology

• Iron homeostasis in the body is primarily regulated through mechanisms of iron absorption.
• Iron is absorbed through duodenal enterocytes and then transported to the liver. Hepcidin is synthesized by the liver and is the major regulator of iron absorption. The amount of dietary iron that is absorbed is relatively low but varies depending on the patient’s iron stores.
• The body loses about 1 to 2 mg/day of iron through loss of intestinal epithelia. This amount is higher in menstruating females.
• IDA usually develops from absorption that is inadequate to compensate for excretion and the demands required for growth (in children).
• Hemoglobin is made up of two alpha globin chains and two beta globin chains. Abnormalities in the production of these chains can lead to microcytic anemia. Anemia can develop either through inadequate production of one of these chains or through increased clearance of red blood cells (RBCs) with mutated globin chains
• Disturbed iron utilization results from lead poisoning or sideroblastic anemia.

Etiology

• The most common cause of microcytic anemia is iron deficiency.
• Hemoglobinopathies are the next most common cause in childhood. Of the hemoglobinopathies, hemoglobin E and α- and β-thalassemias most commonly cause microcytic anemia.
• Rarely, disorders of heme synthesis such as dyserythropoietic anemias and sideroblastic anemia can be a cause of microcytic anemia.
• Anemia of chronic disease can occasionally be microcytic, although more frequently is normocytic.