Macrocytosis in adults is defined as a red blood cell (RBC) mean corpuscular volume (MCV) > 100 femtoliter (fL). Macrocytic anemias are classified into megaloblastic and non-megaloblastic types. Megaloblastic anemia is due to deficiencies or impaired utilization of vitamin B12 and/or folate, whereas non-megaloblastic macrocytic anemia can result from various diseases, such as myelodysplastic syndrome (MDS), liver dysfunction, alcoholism, hypothyroidism, certain drugs, and inherited disorders of DNA synthesis. Differentiating between these types is crucial as treatments are cause-specific.

Megaloblastic anemia (MA) is a type of macrocytic anemia characterized by the presence of abnormally large red blood cell precursors, known as megaloblasts, in the bone marrow. This condition results from impaired DNA synthesis, leading to inhibited nuclear division while cytoplasmic maturation, which depends on RNA and protein synthesis, is less affected. This discrepancy causes an asynchronous maturation between the nucleus and cytoplasm of erythroblasts, leading to the formation of large megaloblasts .

Pathophysiology

The fundamental issue in megaloblastic anemia is impaired DNA synthesis. This impairment primarily affects rapidly dividing cells, such as those involved in hematopoiesis and the gastrointestinal tract, resulting in large, immature red blood cells. Here's a more detailed explanation of the pathophysiology:

1. Impaired DNA...