Microcytic Anemias

Anemias in which the MCV is < 80 femtoliters.

In the elderly, common microcytic anemias include iron deficiency anemia and thalassemia minor. Anemia of chronic disease may be microcytic but is more commonly normocytic. Myelodysplastic syndromes may also be microcytic or normocytic or even macrocytic.

Iron Deficiency Anemia

Normally, total body and bone marrow iron stores increase with age, because the body cannot eliminate excessive iron. Therefore, iron deficiency is never normal in elderly persons, although iron deficiency anemia is common in persons > 65.

Dietary iron deficiency in adults is virtually unknown in the USA, and iron malabsorption occurs only after total gastrectomy or with severe, generalized malabsorption. If these conditions do not exist, iron deficiency implies blood loss, most commonly from the gastrointestinal (GI) or genitourinary tract, and evaluation is necessary. Common sources of chronic occult or other bleeding in the elderly include carcinoma, ulcer, atrophic gastritis, gastritis from drug ingestion, postmenopausal vaginal bleeding, bleeding hemorrhoids, recurrent hemoptysis, and angiodysplasia of the colon.

Symptoms and Signs

The principal symptoms are those of anemia, although mild disease may be asymptomatic. Symptoms related to the cause, such as melanotic stools, acid reflux, and weight loss, may also occur and give clues to the etiology. Atrophy of the tongue and buccal mucosa as well as angular stomatitis may occur. Abnormalities of the gastric mucosa, especially superficial gastritis, frequently develop. Iron deficiency may lead to central nervous system dysfunction. Fatigue, irritability, and decreased cognitive function have been reported in children, but whether they occur in the elderly is unknown.

Diagnosis

Iron deficiency anemia is characterized by small, pale RBCs and depleted iron stores. The peripheral blood smear is populated with microcytic hypochromic cells, and the MCV, the mean corpuscular Hb, and the mean corpuscular Hb concentration are usually reduced. In early iron deficiency, however, these values may still be normal. Many elderly persons with iron deficiency anemia and chronic disease have normal RBC indices and distribution width.

A transferrin saturation ratio (serum iron to total iron-binding capacity [TIBC]) of < 16% may indicate iron deficiency. However, this ratio frequently is not useful because serum iron and TIBC decrease with age and in cases of chronic disease.

Serum ferritin levels usually accurately reflect bone marrow iron stores. However, infection, inflammation, liver disease, and states of increased RBC turnover (eg, ineffective erythropoiesis and hemolysis) can falsely elevate these levels. Serum ferritin levels < 10 µg/L are diagnostic of iron deficiency.

If a conclusive diagnosis of iron deficiency still cannot be made, a bone marrow aspirate stained for iron may be performed. In iron deficiency, iron is either present in trace amounts or is absent. Another option is to give a 1-month trial of oral iron in the form of ferrous salts. If the anemia results from iron deficiency, both Hb and Hct will increase. If no increase occurs, either the patient is not iron deficient, blood loss is exceeding new blood formation, an inflammatory or malignant process is contributing to the anemia, or the patient has protein-energy malnutrition.

For all patients, stools should be screened for occult blood. When iron deficiency is discovered, additional GI tract evaluation (ie, barium studies or endoscopy) may be necessary but depends on the individual patient.

Treatment

Treatment involves finding and eliminating the source of bleeding and correcting the iron deficiency. Oral iron therapy is inexpensive, safe, and convenient. Only ferrous iron salts should be used; enteric-coated and sustained-release preparations are not well absorbed because they are transported past the duodenum, where most iron absorption occurs. One 300-mg tablet of ferrous sulfate contains 60 mg of elemental iron. A single daily dose generally provides enough iron and reduces the likelihood of constipation and gastric irritation; increasing the dose increases iron absorption only minimally. Liquid preparations are available for patients unable to swallow tablets. Many frail elderly patients are unable to tolerate ferrous sulfate because of GI symptoms (including constipation), but they may be able to tolerate a polysaccharide-iron complex, 1 tablet/day, which provides 150 mg of elemental iron. Therapeutic response is monitored by serially measuring serum Hb, Hct, and ferritin levels. Reticulocyte response should begin within 1 to 2 weeks; however, >= 6 months (often up to 1 year) of therapy usually is needed after bleeding has stopped to fully replenish iron stores.

Parenteral iron may be used for patients who have severe malabsorption, who cannot tolerate oral iron, or when iron losses exceed what can be replaced orally (eg, during continued bleeding). Parenteral iron is available as iron dextran and may be given IV or by deep IM injection into the buttocks using the Z-track technique to avoid tissue staining. A test dose of 0.5 mL IV or IM should be given before treatment begins, because this therapy has been associated with anaphylactic shock. Other adverse effects include pain at the injection site, fever, and arthralgias. The maximum recommended dosage is 2 mL/day, which delivers 100 mg of elemental iron. A daily IV infusion should be given at a rate of <= 1 mL/minute for about 2 minutes (2 mL/day) until iron is replenished.

The most expensive and potentially hazardous way to replace iron is by transfusion. Each milliliter of transfused RBCs delivers 1 mg iron.

Thalassemia Minor

Thalassemia minor occurs in persons who are heterozygous for genes that produce few or no - or -globin chains. Because thalassemia minor is asymptomatic, the microcytosis throughout life may have been overlooked or misdiagnosed as iron deficiency; thus it is not unusual to have thalassemia minor diagnosed in old age. Other anemias caused by abnormal Hbs are usually diagnosed in younger persons, because they are symptomatic or the patient has a more pronounced anemia.

Thalassemia minor produces microcytosis with or without mild anemia. The reticulocyte count is usually normal, and serum iron, TIBC, and serum ferritin are normal. Hb electrophoresis may reveal an increase in the minor Hbs, particularly fetal Hb or Hb A₂ in -thalassemia; Hb electrophoresis may be normal in -thalassemia. No treatment is required for thalassemia minor, and iron therapy is contraindicated because it may cause iron overload.