Macrocytic anemia with hypersegmented neutrophils is most classically associated with deficiency of which vitamin?

• A. Vitamin B12
• B. Vitamin B6
• C. Vitamin C
• D. Vitamin A

Answer: (B)

Macrocytic, or megaloblastic, anemia with hypersegmented neutrophils happens when DNA synthesis in rapidly dividing cells is impaired. The classic vitamin deficiency linked to this pattern is vitamin B12. Without enough B12, cells cannot properly convert homocysteine to methionine and methylmalonyl-CoA to succinyl-CoA, so DNA synthesis slows and blood cell precursors in the bone marrow become large and immature. This leads to macrocytosis and hypersegmented neutrophils. Folate deficiency can produce a similar picture, but B12 deficiency also often has neurologic symptoms due to demyelination. The other vitamins listed do not cause this pattern: B6 deficiency tends to cause microcytic sideroblastic anemia, C deficiency causes scurvy, and A deficiency causes vision and other systemic problems.