The Mean Corpuscular Volume (MCV) is a measurement included in a routine complete blood count that reflects the average size of red blood cells (RBCs). When the MCV is elevated, typically above 100 femtoliters (fL), it indicates that the red blood cells are abnormally large, a condition known as macrocytosis. Macrocytosis is a laboratory finding, not a disease itself, signaling an underlying issue with how the body is producing or maintaining these cells. Determining the cause of an elevated MCV is necessary, as the reasons range from correctable nutritional deficiencies to complex organ or bone marrow disorders.
Macrocytosis Caused by B12 and Folate Deficiencies
Deficiencies in Vitamin B12 (cobalamin) and Folate (Vitamin B9) are the most common causes of macrocytosis, leading to a specific type called megaloblastic anemia. These two B vitamins are essential cofactors in DNA synthesis.
When either B12 or Folate is lacking, red blood cell precursors in the bone marrow cannot properly synthesize DNA for cell division. The cell’s cytoplasm continues to mature and grow, resulting in a large, immature cell with delayed nuclear development. These oversized cells, known as megaloblasts, are released into the bloodstream, where they are measured as an elevated MCV.
A B12 deficiency may result from dietary restrictions, particularly in vegans. More frequently, it is caused by pernicious anemia, where the stomach fails to produce intrinsic factor, a protein required for B12 absorption. Folate deficiency usually stems from inadequate dietary intake, malabsorption, or conditions that increase the body’s folate requirement, such as pregnancy. Macrocytosis caused by these deficiencies often presents with extremely high MCV values, sometimes exceeding 120 fL.
Macrocytosis Related to Liver Disease and Alcohol Consumption
Chronic alcohol consumption is a widespread cause of elevated MCV, even in the absence of nutritional deficiencies. Alcohol itself has a direct toxic effect on the erythroid precursor cells in the bone marrow, interfering with the normal maturation process and leading to the release of larger cells. This mechanism is distinct from the DNA synthesis failure seen in B12 and Folate deficiency, resulting in non-megaloblastic macrocytosis. The macrocytosis caused by alcohol often stabilizes in the range of 100 to 110 fL and is reversible with sustained abstinence.
Liver disease, particularly cirrhosis, also causes macrocytosis through a different pathway involving red blood cell membrane composition. Advanced liver dysfunction leads to defective cholesterol esterification and altered blood lipid profiles. These excess lipids then deposit onto the surface of the red blood cell membrane, physically increasing the cell’s surface area and volume. Macrocytosis is highly common in alcoholic liver disease, but it can also occur in non-alcoholic liver diseases due to this lipid alteration mechanism.
Macrocytosis Due to Medications
A number of commonly prescribed medications can cause macrocytosis by interfering with the process of red blood cell production. These drugs often mimic the effects of B12 or Folate deficiency by disrupting DNA synthesis. Examples include chemotherapy agents, such as methotrexate, which directly inhibit the enzymes needed for folate metabolism. Certain antiviral drugs used to treat HIV, like zidovudine, and some seizure medications also interfere with DNA production, leading to the creation of oversized red blood cells.
Bone Marrow Conditions
The elevated MCV can also signal an intrinsic problem within the bone marrow. Myelodysplastic Syndromes (MDS) are a group of disorders where the bone marrow produces defective, dysfunctional blood cells, which are often abnormally large. Aplastic anemia, a condition where the marrow fails to produce enough blood cells, can also present with mild macrocytosis. These primary bone marrow disorders are typically suspected when macrocytosis is accompanied by low counts of other blood cell types, such as white blood cells or platelets.
Investigating Elevated MCV
When an elevated MCV is detected on a complete blood count, the first step involves a comprehensive review of the patient’s history. This includes questions about dietary habits, the amount and frequency of alcohol consumption, and a thorough list of all current medications.
Further laboratory testing is necessary to pinpoint the underlying mechanism. Standard follow-up tests include measuring serum levels of Vitamin B12 and Folate, ordering liver function tests, and performing a thyroid-stimulating hormone (TSH) test, as an underactive thyroid can also cause macrocytosis. Examining a peripheral blood smear reveals the morphology of the red cells, helping distinguish between megaloblastic and non-megaloblastic causes. The Red Cell Distribution Width (RDW), a measure of variation in red blood cell size, is also considered, as a high RDW often accompanies nutritional deficiencies.