Pediatric Megaloblastic Anemia Workup
- Author: James L Harper, MD; Chief Editor: Max J Coppes, MD, PhD, MBA more...
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. 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.[8]
Modified Schilling Test
When vitamin B-12 deficiency is suspected, a Schilling test may be 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.
The Schilling test may be modified to avoid the need for radiolabeled B-12 by measuring B-12 levels before and after a known B-12 dose, followed by a similar test using B-12 with accompanying IF. A comparison of B-12 levels allows detection of a deficiency of either IF or IF-binding protein.
The significance of Schilling test results is as follows:
- Elevation of the B-12 level with oral B-12 -Dietary insufficiency
- Elevation in B-12 levels with oral B-12 and IF - Deficiency of IF (ie, pernicious anemia)
- No improvement with B-12 and IF - Either no absorption in the ileum or transport carrier protein deficiency
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