Macrocytosis and macrocytic anemia. Macrocytic anemia refers to anemia (Hb < 12 g/dL in women, Hb < 13 g/dL in men) in which the mean cell volume is > 100 fL. The first branch point in the diagnostic algorithm is whether the macrocytosis is megaloblastic or non-megaloblastic. The distinction depends on the definition of megaloblastic, which ranges from frank nuclear: cytoplasmic asynchrony in erythroid progenitor cells in the bone marrow (a procedure that is rarely carried out today in this context) to hypersegmented neutrophils on the peripheral smear or simply inhibition of DNA synthesis. There is no question that vitamin B12 and folate deficiency belong in this category. However, which drugs fall under the megaloblastic label is debated. On the non-megaloblastic side are 5 major categories, including spurious (artefactual) physiologic, liver/alcohol, bone marrow disorders and other. COPD and CKD may come as a surprise to some, but there are in fact data indicating an association with macrocytosis. Two final points: 1) macrocytosis can occur in the absence of anemia, as may occur with hydroxyurea use and alcohol abuse, and 2) macrocytosis may remain unexplained despite extensive workup.
