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Macrocytic anemia is divided into megaloblastic and nonmegaloblastic causes, with the former being more common. Megaloblastic anemia results from impaired DNA synthesis, leading to release of megaloblasts, which are large nucleated red blood cell precursors with chromatin that is not condensed. Vitamin B12 deficiency is the most common cause for megaloblastic anemia, although folate deficiency also can contribute. Nonmegaloblastic anemia entails normal DNA synthesis and typically is caused by chronic liver dysfunction, hypothyroidism, alcohol use disorder, or myelodysplastic disorders. Macrocytosis also can result from release of reticulocytes in the normal physiologic response to acute anemia. Management of macrocytic anemia is specific to the etiology identified through testing and patient evaluation.

Case 3. ZT is a 76-year-old patient with diabetes who comes to your office for an annual wellness visit and review of laboratory test results. He reports mild fatigue and intermittent tingling in his feet. He takes metformin 1,000 mg 2 times/day. Morning fasting blood glucose levels have been 100 to 120 mg/dL. The hemoglobin level is low at 11.8 g/dL. The mean corpuscular volume is elevated at 101 mcm3 .

Definition and Parameters

Macrocytic anemia is a common condition frequently found on screening laboratory results.23 It is defined by a hemoglobin, hematocrit, or red blood cell (RBC) level that is less than the laboratory reference range coupled with a mean corpuscular volume (MCV) that is greater than 100 mcm3.21 The causes of macrocytic anemia are classified as megaloblastic anemias, characterized by the presence of large dysfunctional RBCs (megaloblasts) and hyper-segmented neutrophils on a peripheral blood smear, and nonmegaloblastic anemias, when these cells are absent. Less commonly, macrocytosis can be caused by reticulocytosis, which is an increase in immature RBCs.21,79

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