Approach Considerations
Hematologic testing confirms the presence of megaloblastic anemia and can exclude neoplastic and other disorders.
Assess for vitamin B-12 and folate levels.
Other tests include serum and urine assessments and the modified Schilling test.
Hematologic Evaluation
The CBC reveals macrocytic red cell indices and evaluates for other cytopenias. Pancytopenia has been observed in severe cases of megaloblastic anemia.
The manual differential is essential to rule out the possibility of circulating blast cells, which may be present in a patient with leukemia who presents with pancytopenia. A platelet count may be indicated.
The reticulocyte count is important in the assessment of red cell production.
Examination of the peripheral blood smear shows macrocytosis. Hypersegmented neutrophils (in which the nucleus has 6 or more segments) can usually be observed as well.
Consider bone marrow evaluation for any child with more than one abnormal cell line on the CBC. It can help to rule out other disorders such as leukemia, myelodysplasia, and aplastic anemia. Bone marrow in patients with megaloblastic anemia demonstrates the red blood cell precursor nuclear/cytoplasmic asynchrony. [15] Granulocyte precursors may also be abnormal.
Vitamin B-12 and Folate Assessment
Measure serum vitamin B-12 levels. Methylmalonic acid and total homocysteine levels are sensitive indicators of vitamin B-12 deficiency and correlate with clinical abnormalities and therapeutic response. However, they are not specific to vitamin B-12 deficiency, and care should be taken in interpreting these results.
For folate assessment, the RBC folate level is the best measure of metabolically active folate and includes 5-methyl tetrahydrofolate (THF) in the assay. Serum folate measures the circulating pool of folate but does not accurately reflect the amount of THF present in the tissues.
Serum and Urine Assessment
Serum chemistries should include albumin and total protein measurement.
Serum chemistry studies allow assessment of protein loss and nutritional status.
Urinalysis should be performed for protein and creatinine.
Measurement of urine proteins and intrinsic factor (IF), if possible, detects Imerslund-Grasbeck syndrome. [16]
Modified Schilling Test
When vitamin B-12 deficiency is suspected, a Schilling test was classically performed to determine whether congenital absence of a binding protein is present. However, the classical nuclear medicine Schilling test is not commonly available due to the unavailability of radiolabeled B-12.
Measurement before and after an oral dose of vitamin B-12 can demonstrate absorption and eliminate malabsorption from the differential for the patient. An abnormal result (not showing an increase in serum vitamin B-12) would indicate need for further evaluation for causes of malabsorption.
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Bone marrow aspirate from a patient with untreated pernicious anemia. Megaloblastic maturation of erythroid precursors is shown. Two megaloblasts occupy the center of the slide with a megaloblastic normoblast above. Photo courtesy of Marcel E Conrad, MD.
