Which of the following findings is most characteristic of megaloblastic anemia on blood smear?

• A. Burr cells
• B. Target cells
• C. Spherocytes
• D. Hypersegmented neutrophils

Answer: (D)

Megaloblastic anemia on smear is driven by impaired DNA synthesis from B12 or folate deficiency, which causes nuclear maturation to lag behind cytoplasmic development. This nuclear-cytoplasmic asynchrony leads to characteristic abnormal white cells, especially neutrophils with hypersegmented nuclei. Hypersegmented neutrophils—nuclei with more than the usual number of lobes (often five to six)—are the hallmark finding because they reflect the disrupted, asynchronous maturation of precursors. Macrocytosis with oval macrocytes is common, and there may be accompanying anisocytosis, but the defining smear feature is hypersegmented neutrophils.

Other smear findings listed point to different conditions: burr cells (spur cells) appear in liver disease or uremia; target cells are seen in liver disease, thalassemias, or hemoglobinopathies; and spherocytes occur in hereditary spherocytosis or autoimmune hemolytic anemia.