Which anemia is commonly associated with hypersegmented neutrophils on peripheral smear?

• A. Aplastic anemia
• B. Folate deficiency anemia
• C. Pernicious anemia
• D. Iron deficiency anemia

Answer: (D)

Hypersegmented neutrophils reflect a problem with DNA synthesis during white cell development. When folate or vitamin B12 is deficient, thymidine synthesis is impaired so nuclear maturation lags behind cytoplasmic maturation, producing megaloblastic changes. In the peripheral smear, neutrophils commonly have five or more lobes due to this disrupted maturation. Pernicious anemia is a classic cause of vitamin B12 deficiency (autoimmune loss of intrinsic factor), so it frequently presents with hypersegmented neutrophils. Folate deficiency can cause the same megaloblastic changes as well. By contrast, iron deficiency anemia is microcytic and hypochromic and does not produce hypersegmented neutrophils, since it does not involve impaired DNA synthesis in neutrophil precursors.