Condensed Case

The patient in this study is a 73-year-old woman who has anemia of long standing. She had always been a poor eater. Peripheral smears have consistently shown hypochromia with target and many Howell-Jolly bodies. She has no surgical history and she shows no blood loss through either the gastrointestinal or genitourinary tract. Her lab results are WBC of 2.7 X 109/L, RBC 2.25 X 1012/L, Hgb 7.8 g/dL, Hct 23%, and MCV 111 fL. Based on these findings, what is your initial clinical impression?


This patient most likely has a megaloblastic anemia. Her age, dietary habits, and complete blood count can lead to that impression. With her dietary history, she may have initially had an iron deficiency condition, and her peripheral smear results seem to verify that. However, it seems as if her condition has shifted toward a vitamin B12 or folic acid deficiency. Serum vitamin B12 and folic acid assays should be ordered, and a Schilling test may be considered to rule in or rule out an intrinsic factor deficit.

Summary Points

• Macrocytic anemias have an MCV of greater than 100 fL and a normal MCHC.

• Megaloblastic anemias are macrocytic anemias in which vitamin B12 and/or folic acid is deficient.

Not all macrocytic anemias are megaloblastic.

Vitamin B12 and folic acid deficiencies lead to impaired DNA synthesis.

The bone marrow in megaloblastic anemias is hypercellular with the red cell precursors showing distinct chromatin and cytoplasmic changes.

• Megaloblastic anemias show ineffective erythropoie sis in the bone marrow: premature destruction of red cell precursors before delivery into the circulation.

• The peripheral smear in megaloblastic anemia shows macrocytes, oval macrocytes, and hyperseg-mented neutrophils.

• Pancytopenia and reticulocytopenia are prominent features of the megaloblastic processes.

• Patients with megaloblastic anemia may exhibit symptoms of anemia as well as neurological symptoms, such as numbness or difficulty walking.

• Intrinsic factor, secreted by the parietal cells of the stomach, is necessary for vitamin B12 to be absorbed.

• Intrinsic factor deficiency can lead to pernicious anemia, a subset of megaloblastic anemia.

• Intrinsic factor deficiency may develop because intrinsic factor is not being secreted or because it is being blocked or neutralized.

• Ninety percent of individuals experiencing pernicious anemia have parietal cell antibodies.

• Folic acid deficiency is the most common vitamin deficiency in the United States.

• Serum B12, folic acid, and red cell folate can be determined by radioimmunoassay.

• Individuals with vitamin B12 deficiency will require lifelong therapy.

• Folic acid deficiency requires short-term therapy.

• The Schilling test is used to determine whether there is faulty absorption of vitamin B12. Deficiency is the result of intrinsic factor or malabsorption syndrome.

• There are causes of a macrocytic anemia other than megaloblastic processes.

• Macrocytes may be seen in reticulocytosis, alcoholism, or liver disease.

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