Megaloblastic Anemia

Excerpt

Megaloblastic anemia (MA) encompasses a heterogeneous group of macrocytic anemias characterized by the presence of large red blood cell precursors called megaloblasts in the bone marrow. This condition is due to impaired DNA synthesis, which inhibits nuclear division. Cytoplasmic maturation, mainly dependent on RNA and protein synthesis, is less impaired. This leads to an asynchronous maturation between the nucleus and cytoplasm of erythroblasts, explaining the large size of the megaloblasts. The process affects hematopoiesis as well as rapidly renewing tissues such as gastrointestinal cells. Megaloblastic anemia is most often due to hypovitaminosis, specifically vitamin B12 (cobalamin) and folate deficiencies, which are necessary for the synthesis of DNA. Copper deficiency and adverse drug reactions (due to drug interference with DNA synthesis) are other well-known causes of megaloblastic anemia. A rare hereditary disorder known as thiamine-responsive megaloblastic anemia syndrome (TRMA) is also identified as a cause of megaloblastic anemia. The list of drugs associated with the disease is long however, frequently implicated agents include hydroxyurea, chemotherapeutic agents, anticonvulsants, and antiretroviral therapy (ART) drugs.