Megaloblastic Anemia

Macrocytes are defined as RBCs with a mean corpuscular volume (MCV) >100 femtoliter (fL). Megaloblastic anemia (MA) is a form of anemia that results from a variety of reasons, which produce enlarged red blood cell (RBC) precursors in the bone marrow, namely megaloblasts, and macrocytes in peripheral blood. Megaloblasts occur because of asynchronous maturation between the nucleus (dependent on DNA synthesis) and cytoplasm (dependent on RNA and protein synthesis), during which the cytoplasm increases more rapidly than the nucleus, leading to an increase in cell size. The leading causes of MA include deficiencies in cobalamin (vitamin B12) and folate or folic acid. These two nutrients are essential in biochemical processes that lead to ATP generation (Krebs Cycle) and DNA synthesis, both of which are critical for cell growth and tissue generation. The other etiologies leading to MA include myelodysplastic syndrome/neoplasms (MDS), liver dysfunction, alcoholism, hypothyroidism, copper deficiency, and certain drugs that interfere with DNA synthesis. Rarely, it is caused by a hereditary disorder called thiamine-responsive megaloblastic anemia (TRMA).