The most common cause of macrocytic anemia is megaloblastic anemia, which is the result of impaired DNA synthesis. Although DNA synthesis is impaired, RNA synthesis is unaffected, leading to a buildup of cytoplasmic components in a slowly dividing cell.This results in a larger-than-normal cell.itamin B-12 deficiency is a cause of macrocytosis. Because DNA synthesis requires cyanocobalamin (vitamin B-12) as a cofactor, a deficiency of the vitamin leads to decreased DNA synthesis in the erythrocyte, thus resulting in macrocytosis.