Which morphological classification is characteristic of megaloblastic anemia?

If megaloblastic anemia is suspected based on clinical features and the results of the CBC and peripheral smear, evaluation for possible drug-induced megaloblastic anemia through a detailed medical history is recommended. If the megaloblastic anemia is not drug induced, testing for vitamin deficiencies should be considered.

Evaluation for Vitamin Deficiency

and/or deficiency may result in megaloblastic anemia. Because vitamin B12 deficiency is much more common than folate deficiency, the evaluation should commence with tests for vitamin B12, or a combined vitamin B12/folate test can be used.

Vitamin B12 Deficiency Testing

Testing for begins with a serum concentration test. Follow-up testing depends on the result of this test. The patient’s use of vitamin B12 injections should be considered when interpreting test results, given that serum vitamin B12 concentration may be affected by injections administered within approximately 2 weeks of specimen collection.

aIf suspicion for vitamin B12 deficiency persists in a patient with a vitamin B12 concentration >400 pg/mL, consider MMA and homocysteine tests.

MMA, methylmalonic acid

Source: Green, 2017

The MMA test is a sensitive and specific indicator of vitamin B12 deficiency that can be used if the serum vitamin B12 concentration is borderline. An elevated MMA concentration (>0.4 µmol/L) confirms vitamin B12 deficiency. Plasma homocysteine levels may also be increased in vitamin B12 deficiency, although this test is not specific. If vitamin B12 deficiency is confirmed, evaluation for is recommended. For additional information on vitamin B12 and MMA tests, see the ARUP Consult topic.

Folate Deficiency Testing

Testing for folate deficiency should begin with a serum or plasma folate test. A serum or plasma folate concentration <4 µg/L indicates folate deficiency. If results are not conclusive, an RBC folate test can be performed, followed by a homocysteine test if the concentration of folate is borderline. Although the homocysteine test is not specific, an increased homocysteine level is consistent with folate deficiency. For additional information on these tests, see the ARUP Consult topic.

Evaluation for Pernicious Anemia

The majority of patients with pernicious anemia have antibodies for parietal cells and IF. In patients with confirmed vitamin B12 deficiency, testing for pernicious anemia is recommended. In patients with borderline vitamin B12 and MMA test results, this testing is considered optional.

Intrinsic Factor Blocking Antibody Testing

Antibodies to IF are specific to pernicious anemia and are present in the majority of patients. A positive IF antibody test confirms pernicious anemia.

Parietal Cell Antibody Testing

Parietal cell antibody tests are more sensitive than IF antibody tests, but parietal cell antibodies are less specific to pernicious anemia and may be seen in chronic gastritis. A positive parietal cell antibody test following a negative IF test in the appropriate clinical context confirms the diagnosis of pernicious anemia.

Serum Gastrin Testing

Gastrin concentration is generally elevated in pernicious anemia but may be increased in other conditions as well. Gastrin testing can be considered to indirectly confirm pernicious anemia if a parietal cell antibody test is negative but suspicion for pernicious anemia persists.

Other Testing

The Schilling test is an obsolete test that measures the enteral absorption of vitamin B12; it is not generally available. The deoxyuridine suppression test uses radioactive deoxyuridine to assess vitamin B12 and folate status. This test may be useful in some patients if other tests fail to diagnose vitamin B12 or folate deficiency. Bone marrow biopsy may also be considered if other tests fail to yield a diagnosis.

ARUP Laboratory Tests

Initial Evaluation

Use to evaluate cellular morphology

Evaluation for Vitamin Deficiency

Aids in the detection of vitamin B12 deficiency

For patients with known risk factors for folate deficiency, consider Vitamin B12 and Folate test

Preferred reflex test for detection of vitamin B12 deficiency in individuals with macrocytic or unexplained anemia

Reflex pattern – if vitamin B12 is <300 pg/mL, methylmalonic acid, serum will be added

Use to evaluate vitamin B12 deficiency

Use to confirm vitamin B12 or folate deficiency

Use to detect vitamin B12 or folate deficiency

Aids in the detection of vitamin B9 (folate) deficiency

Evaluation for Pernicious Anemia

Use to confirm pernicious anemia as etiology of megaloblastic anemia

Use to evaluate pernicious anemia or immune-mediated deficiency of vitamin B12

Indirectly confirms pernicious anemia

References

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Lanier JB, Park JJ, Callahan RC. Anemia in older adults. Am Fam Physician. 2018;98(7):437-442.

28189172

Green R, Datta Mitra A. Megaloblastic anemias: nutritional and other causes. Med Clin North Am. 2017;101(2):297-317.

Practical Diagnosis of Hematologic Disorders - 5th edition

Kjeldsberg, CR, ed. Practical Diagnosis of Hematologic Disorders. 5th ed. American Society for Clinical Pathology; 2010.

26886541

Hesdorffer CS, Longo DL. Drug-induced megaloblastic anemia. N Engl J Med. 2016;374(7):696-697.

24424200

Bizzaro N, Antico A. Diagnosis and classification of pernicious anemia. Autoimmun Rev. 2014;13(4-5):565-568.

Additional Resources

Related Information From ARUP Laboratories

Topics From ARUP Consult

Anemia

Hemolytic Anemias

Iron Deficiency Anemia

Vitamins - Deficiency and Toxicity

Selected Scholarly Publications From ARUP Laboratories

Related Algorithms

Educational Videos From ARUP Laboratories

Diagnostic Approach to Anemia

75 min

Medical Experts

Contributor

Doyle

Kelly Doyle, PhD, DABCC, FAACC

Associate Professor of Pathology (Clinical), University of Utah

Medical Director, Special Chemistry and Endocrinology, ARUP Laboratories

Contributor

Frank

Elizabeth L. Frank, PhD, DABCC

Professor of Pathology (Clinical), University of Utah

Medical Director, Analytic Biochemistry, Calculi and Manual Chemistry; Co-Medical Director, Mass Spectrometry, ARUP Laboratories

Which morphological classification is characterized of megaloblastic anemia?

Megaloblastic anemia (MA) encompasses a heterogeneous group of macrocytic anemias characterized by the presence of large red blood cell precursors called megaloblasts in the bone marrow.

What are the characteristics of megaloblastic anemia?

Megaloblastic anemia is a type of anemia characterized by very large red blood cells. In addition to the cells being large, the inner contents of each cell are not completely developed. This malformation causes the bone marrow to produce fewer cells, and sometimes the cells die earlier than the 120-day life expectancy.

Is megaloblastic anemia Macrocytic or Microcytic?

Megaloblastic anemia is a form of macrocytic anemia. Macrocytic anemia is a blood disorder that causes your bone marrow to make abnormally large red blood cells. It's also a type of vitamin deficiency anemia. This condition happens when you don't get enough vitamin B12 and/or vitamin B9 (folate).

Which of the following is most suggestive of a megaloblastic anemia?

An elevated reticulocyte maturation value is more suggestive of a megaloblastic rather than a non-megaloblastic anemia.