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Anemia, a decrease in the number of red blood cells (RBCs), hemoglobin (Hb) content, or hematocrit (Hct), can result from decreased RBC production (erythropoiesis), increased RBC destruction, blood loss, or a combination of these factors. (See also Approach to the Patient with Anemia.)

Anemias due to decreased erythropoiesis (termed hypoproliferative anemias) are recognized by a reticulocyte count that is inappropriately low for the degree of the anemia.

The RBC indices, mainly the mean corpuscular volume (MCV), can narrow the differential diagnosis of deficient erythropoiesis and help determine what further testing is necessary.

Microcytic anemias result from deficient or defective heme or globin synthesis. Microcytic, hypoproliferative anemias include

• Iron deficiency anemia

• Iron-transport deficiency anemias

• Iron-utilization anemias (including some sideroblastic anemias and lead poisoning)

Patients with a microcytic anemia typically require evaluation of iron stores.

Normocytic anemias are characterized by a normal MCV (80 to 100 fL) and normochromic indices. The two most common causes are

• Hypoproliferation due to a deficiency of or inadequate response to erythropoietin (EPO) due to inflammation or renal disease

• The anemia of chronic disease or inflammation (although, if severe, can be microcytic)

Acquired primary bone marrow disorders such as aplastic anemia, pure red cell aplasia, and myelodysplastic syndrome (MDS) can also manifest with a normocytic anemia.

Macrocytic anemias can be caused by impaired DNA synthesis leading to megaloblastosis, as occurs with

• Deficiencies of vitamin B12 or folate (see Megaloblastic Macrocytic Anemias)

Other causes of macrocytic anemia include

• Chronic alcohol intake

• Medications (eg, zidovudine, azathioprine, methotrexate, hydroxyurea, imatinib) or toxins

• Hemolysis with reticulocytosis

• Liver disease

• Myelodysplastic syndromes (MDS)

Some patients with hypothyroidism have macrocytic RBC indices, including some without anemia.

Anemias can have variable findings on the peripheral smear. The anemia of chronic disease may be microcytic or normocytic. Anemias due to myelodysplastic syndromes may be normocytic, macrocytic, or even microcytic. Anemias due to endocrine disorders (such as hypothyroidism) or elemental deficiencies (eg, copper deficiency) can have variable manifestations, including a microcytic, normocytic, or macrocytic anemia.

Treatment of deficient RBC production depends on the cause.