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South Med J. 2013 Feb;106(2):121-5. doi: 10.1097/SMJ.0b013e3182824cdf.

Unexplained macrocytosis.

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  • 1Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202, USA.



Macrocytosis is a relatively common finding in adult patients undergoing blood cell counting. Approximately 10% of patients will have unexplained macrocytosis after laboratory evaluation. Data on the approach to patients with unexplained macrocytosis are limited.


To investigate this topic and help delineate an approach to this condition, the records of 9779 patients diagnosed in our institution between 1995 and 2005 as having macrocytosis were reviewed. Patients with evidence of liver disease, alcohol abuse, hypothyroidism, folate or vitamin B12 deficiency, hemolysis, or use of any drugs known to cause macrocytosis were excluded.


Forty-three patients were found to have unexplained macrocytosis. The median follow-up was 4 years. A total of 11.6% patients developed a primary bone marrow disorder (two B-cell lymphomas, two with myelodysplastic syndrome, one plasma cell disorder), 16.3% developed worsening cytopenias, 69.7% had stable disease, and 2.3% resolved. The median time to first cytopenia was 18 months, and the mean time to diagnosis of bone marrow disorder was 31.6 months. The outcomes were not significantly different when comparing patients with or without anemia upon diagnosis. The probability of a bone marrow biopsy to establish a diagnosis of a primary disorder was 33.3% in patients with macrocytosis without anemia compared with 75% in patients with macrocytosis with anemia.


Patients with unexplained macrocytosis still require close follow-up. We suggest a strategy of follow-up with blood cell counting every 6 months. Bone marrow biopsy should be performed when cytopenias are present because this approach may provide a higher yield of diagnosis and aid with therapeutic decisions.

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