Which of the following best describes megaloblastic anemia?

• A. RBCs are abnormal and large
• B. RBCs are small and pale
• C. RBC production is accelerated
• D. RBCs are normal size

Answer: (A)

Megaloblastic anemia occurs when DNA synthesis in developing red cells is impaired, usually from B12 or folate deficiency. Because DNA synthesis lags behind cytoplasmic development, the red cells become abnormally large and immature, a feature known as macrocytosis. This makes the description of red blood cells as abnormal and large the best way to characterize megaloblastic anemia. It’s not about small, pale cells (microcytosis from iron deficiency), nor about accelerated production (ineffective erythropoiesis slows or reduces production), nor about normal-sized cells. In practice, you’d also see macrocytosis on a smear, with possible macro-ovalocytes and hypersegmented neutrophils.