Macrocytic anemia with hypersegmented neutrophils and macro-ovalocytes is classic for pernicious anemia. Which smeal feature is most consistent with this diagnosis?

• A. Bite cells
• B. Target cells
• C. Macro-ovalocytes and hypersegmented neutrophils
• D. Spherocytes

Answer: (C)

Macrocytic anemia with hypersegmented neutrophils and macro-ovalocytes reflects a megaloblastic process from vitamin B12 (or folate) deficiency. In pernicious anemia, autoimmune loss of intrinsic factor reduces B12 absorption, impairing DNA synthesis in hematopoietic precursors. This causes delayed nuclear maturation relative to cytoplasmic growth, producing large, oval red cell precursors (macro-ovalocytes) and neutrophils with multiple lobes (hypersegmentation). This smear pattern is the classic clue to megaloblastic anemia from B12 deficiency and helps distinguish it from other red cell abnormalities. Bite cells occur with oxidative damage (e.g., G6PD deficiency), target cells appear in liver disease or certain hemoglobinopathies, and spherocytes are seen in hereditary spherocytosis or autoimmune hemolysis; none of these pair with the macro-ovalocyte/hypersegmented neutrophil pattern characteristic of pernicious anemia.