These abnormalities include the presence of enlarged oval shaped red blood cells (macroovalocytes) and hypersegmented neutrophils (defined as a neutrophil with six or more lobes). Hypersegmented neutrophils may be seen in the absence of macroovalocytes as hypersegmentation of neutrophils is an early sign of megaloblastic anemia and may precede the appearance of macroovalocytes; they may also be seen in other anemias (e.g., iron deficiency anemia) and thus are suggestive of megaloblastic anemia but not specific for it. An increased red cell distribution width (anisocytosis) also suggests megaloblastosis and is commonly seen in Vitamin B12 deficiency and folic acid deficiency. This type of anemia is caused by impaired DNA synthesis and repair, often from deficient thymidine production. Thiamine responsive megaloblastic anemia syndrome also causes megaloblastic anemia.The red blood cells grow larger because they cannot produce DNA quickly enough to divide at the right time as they grow and thus grow too large before division. Additional causes of megaloblastic anemia include medications that interfere with DNA synthesis or with the absorption or metabolism of Vitamin B12 or folate such as methotrexate, sulfasalazine, metformin, anticonvulsant medications (e.g., valproic acid or phenytoin), certain antibiotics (e.g., trimethoprim/sulfamethoxazole), antiretroviral medications, cholestyramine, triamterene,  and nitrous oxide.
The term macrocytic is from Greek words meaning "large cell". A macrocytic class of anemia is an anemia (defined as blood with an insufficient concentration of hemoglobin) in which the red blood cells (erythrocytes) are larger than their normal volume. The normal erythrocyte volume in humans is about 80 to 100 femtoliters (fL= 10−15 L). In metric terms the size is given in equivalent cubic micrometers (1 μm3 = 1 fL). The condition of having erythrocytes which (on average) are too large, is called macrocytosis. In contrast, in microcytic anemia, the erythrocytes are smaller than normal. In a macrocytic anemia, the larger red cells are always associated with insufficient numbers of cells and often also insufficient hemoglobin content per cell. Both of these factors work to the opposite effect of larger cell size, to finally result in a total blood hemoglobin concentration that is less than normal (i.e., anemia). Macrocytic anemia is not a disease in the sense of having a single pathology but, rather, is a condition. As such, it is the class name for a set of pathologies that all produce somewhat the same red blood cell abnormality. Different pathologies result in macrocytic-type anemias. Some of these pathologies produce slightly different sets of appearances in blood cells that are detectable from red and white cell morphology, and others are only detectable with chemical testing. Causes
Megaloblastic anemias
Megaloblastic anemias represent a type of macrocytic anemia characterized by certain morphologic abnormalities noted on a peripheral blood smear examination.