DESCRIPTION

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

EPIDEMIOLOGY

• The prevalence and incidence of microcytic anemia are dependent on the etiology.
• In pediatrics, the three most common causes of microcytic anemia are iron deficiency anemia (IDA), hemoglobinopathies, and anemia of chronic disease.
• Prevalence of IDA by age:
  • Toddler (1 to 3 years old): 15% are iron deficient; 5% have IDA.
  • Adolescent females: 9–16% have IDA.
  • 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.

ETIOLOGY

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

RISK FACTORS

• Prematurity, breastfeeding, low socioeconomic class, and anemia of inflammation are associated with IDA.
• Certain ethnic groups such as African Americans and Hispanics have higher rates of ID. These groups also have a higher incidence of hemoglobinopathies, which can complicate the clinical picture.
• Dietary factors at different ages can lead to a decreased intake of iron.
  • Infants: lack of iron supplementation for exclusively breastfed infants after 4 months of age, unfortified cow’s milk, delayed intake of iron-rich food
  • Toddlers: excessive cow’s milk consumption
  • Adolescents: poor intake of iron-rich food
• Decreased absorption of iron in malabsorptive diseases
• Increased losses in disorders associated with GI bleeding or increased menstrual blood loss

PATHOPHYSIOLOGY

• IDA usually develops from absorption that is inadequate to compensate for excretion and the demands required for growth (in children).
• The body loses about 1 to 2 mg/day of iron through loss of intestinal epithelia. This amount is higher in menstruating females. 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. Iron supplementation acutely increases hepcidin and results in lower iron absorption the next day.
• Inflammation and chronic disease are associated with increased hepcidin levels resulting in decreased iron absorption in the gut as well as reduced release of iron from storage sites.
• Hemoglobin is made up of two α-globin chains and two β-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.
• Microcytic anemia frequently seen in young children with lead poisoning is usually due to concomitant IDA. Pica is a symptom of untreated IDA and also increases the risk of lead ingestion. ID increases lead absorption in the gut, and lead poisoning decreases responsiveness of IDA to oral iron supplementation. Lead poisoning does not itself cause microcytic anemia.