When a complete blood count is obtained, there is now the virtually uniform use of an automated cell count that, by several different methods, measures a parameter that reflects the red blood cell (RBC) volume. This measurement is reported as mean corpuscular volume (MCV) in units of femtoliters (10-15 liters) per RBC. (See "Mean corpuscular volume".) With automated methods, a MCV above 100 femtoliters (fL) is flagged as a high value and is called macrocytosis. Examination of the peripheral smear will confirm the diagnosis, as macrocytic cells are larger than the size of the nucleus of a small lymphocyte (picture 1).
This topic review will discuss the differential diagnosis of an elevated MCV. Such patients may not be anemic but, if they are, the presence of macrocytosis can help to direct the subsequent evaluation. (See "Approach to the adult patient with anemia".)
PATHOPHYSIOLOGY AND ETIOLOGY
Red blood cells (RBCs) enter the circulation from the bone marrow as reticulocytes, which are macrocytic. All other macrocytic RBCs are formed as a consequence of congenital or acquired abnormalities in nucleic acid metabolism of erythroid precursors, changes in membrane structure, alterations in pathways governing cell water content, or other factors (table 1) [1-3]. Conditions causing the production of macrocytic RBCs are broadly grouped into those associated with megaloblastic (eg, folate or cobalamin deficiency) or normoblastic (eg, alcoholism, liver disease, and certain drugs) RBC precursors.
Reticulocytosis — During normal erythropoiesis, when the orthochromic normoblast extrudes its nucleus, the remaining reticulocyte has a volume of 120 to 150 fL. This cell remains in the marrow for approximately three days and then is released into the peripheral blood where it undergoes remodeling with loss of cell water and membrane. Reticulocytes in the peripheral blood have a mean corpuscular volume (MCV) of 103 to 126 fL, a mean corpuscular hemoglobin concentration (MCHC) of 23.5 to 28.7 g/dL, and a mean cell hemoglobin (MCH) of 25.9 to 30.6 (picture 2). These values should be contrasted to normal RBC values:
●MCV = 80 to 96 fL