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How do you evaluate macrocytosis without anemia?

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Liver disease—which may be confounded by alcohol abuse, medications, or cancer—is a common cause of macrocytosis.5 Hypothyroidism is rarely a cause, but may be more prevalent in the elderly.10

What these 2 tests may, or may not, tell you

Although several authorities recommend a peripheral smear and reticulocyte count to help evaluate macrocytic anemia, no specific recommendations exist for these tests in the absence of anemia. A peripheral smear can detect megaloblastic changes typical of B12 and folate deficiency and other marrow disorders, especially myelodysplastic changes. Peripheral smear findings and reticulocytosis can also show evidence of hemolysis. However, megaloblastic changes and marrow-related changes on peripheral smear are typically seen with anemia.

In 2 prospective studies of primary care patients, 1 reported little diagnostic value for the peripheral smear,1 and the other found that reticulocytosis rarely caused macrocytosis.5 A prospective study of 300 hospitalized patients with macrocytosis found that 100% of marrow disorders and hemolysis that caused macrocytosis also caused an associated anemia.7 A retrospective chart review of 113 cases of macrocytosis in outpatients found that general practitioners often didn’t order a peripheral smear and reticulocyte count to complete their diagnostic workups.4

Bone marrow biopsy may reveal dysplastic changes, but not a Dx

A prospective study of the utility of bone marrow biopsy in 124 elderly patients with macrocytosis found that as many as 60% were diagnosed by blood tests alone. All the remaining patients with unexplained macrocytosis underwent bone marrow biopsy, which showed early dysplastic changes in 39%, but did not provide a diagnosis in nearly 50%. Twelve percent were found to have myelodysplastic syndrome, but they had a mean hemoglobin of 8.5 g/dL.10


We were unable to find published guidelines for the evaluation of macrocytosis without anemia by the American Society of Hematology, the British Committee for Standards in Haematology, or in an authoritative hematology text.11


The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the US Government.


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