The Mean Corpuscular Volume (MCV) is a measurement included in a routine Complete Blood Count (CBC). The MCV quantifies the average volume, or size, of the red blood cells (RBCs) in a blood sample. A high MCV indicates the presence of abnormally large red blood cells, a condition known as macrocytosis. This finding is not a diagnosis but a sign that an underlying biological process is influencing blood cell production. This article explains the meaning of an elevated MCV and explores the common nutritional, lifestyle, and systemic factors that can lead to this result.
Defining MCV and Macrocytosis
The MCV is measured in femtoliters (fL). For most adults, the normal reference range typically falls between 80 and 100 fL. When the MCV exceeds this upper limit, generally over 100 fL, the condition is termed macrocytosis, which means “large cells.”
This cellular enlargement can impair the red blood cells’ ability to efficiently carry oxygen. An abnormally large cell volume may lead to premature destruction or ineffective production, potentially contributing to anemia. Because macrocytosis can occur with or without a reduction in the overall number of red blood cells, a high MCV always prompts further investigation.
Primary Nutritional and Lifestyle Causes
The most frequent causes of macrocytosis involve deficiencies in specific B vitamins or exposure to substances that directly impair the bone marrow. These factors often affect DNA production, leading to a defect known as megaloblastic change.
Nutritional Deficiencies
Vitamin B12 (cobalamin) and folate (vitamin B9) are required for DNA synthesis and cell division. When either is lacking, red blood cell precursors in the bone marrow cannot complete nuclear division effectively. This delay in nuclear maturation, while the cytoplasm continues to grow, results in a larger-than-normal cell being released into circulation.
B12 deficiency, often caused by poor absorption, can lead to neurological symptoms like numbness, tingling, or difficulty walking, as B12 is necessary for nervous system health. Folate deficiency, resulting from inadequate dietary intake or certain medications, also causes macrocytosis and general anemia symptoms, such as weakness and shortness of breath. In severe cases of either deficiency, the tongue may become sore, swollen, and smooth (glossitis).
Chronic Alcohol Use
Chronic, heavy alcohol consumption is a common cause of elevated MCV, often due to a two-fold mechanism. First, alcohol interferes with the absorption and utilization of folate and Vitamin B12, leading to nutritional deficiencies. Second, alcohol is a direct toxin to the bone marrow, impairing the production process.
This direct toxicity can cause macrocytosis even when B12 and folate levels appear normal. The elevated MCV resulting from alcohol’s toxic effect is often a sensitive marker of excessive consumption. This form of macrocytosis is generally reversible, but cell size may only return to normal after several months of complete abstinence.
Underlying Systemic and Medication-Related Causes
If nutritional and alcohol-related causes are ruled out, a high MCV may signal an underlying chronic condition or be a side effect of medical treatment. These causes are generally categorized as non-megaloblastic macrocytosis, meaning the enlargement is not due to a defect in DNA synthesis. The mechanisms involve changes to the red blood cell membrane or the rapid release of immature cells.
Systemic Conditions
Severe liver disease frequently results in macrocytosis due to altered lipid metabolism. The dysfunctional liver cannot properly regulate blood cholesterol and phospholipids, causing these lipids to deposit onto the red blood cell membranes. This deposition adds surface area to the cell, making it appear larger in volume. Macrocytosis in this context indicates the severity of the liver dysfunction.
Hypothyroidism, a state of low thyroid hormone activity, is sometimes associated with a mild elevation in MCV. While the exact mechanism is unclear, the slowing of metabolism can affect red blood cell production and turnover. Additionally, the body may release a large number of reticulocytes (young, immature red blood cells) in response to blood loss or excessive red cell destruction. Since reticulocytes are naturally larger than mature cells, their presence can artificially raise the average MCV value.
Medication Side Effects
A number of prescription medications can interfere with the bone marrow’s ability to produce blood cells, leading to macrocytosis. Many of these drugs disrupt rapid cell division, making them useful for treating conditions like cancer. For example, certain chemotherapy drugs, such as methotrexate, act as folate antagonists and interfere with the DNA synthesis pathway.
Other common medications known to cause macrocytosis include anti-seizure medications like phenytoin and antivirals used to treat HIV (e.g., zidovudine). Even the diabetes drug metformin can sometimes lead to a B12 deficiency over time, causing an elevated MCV. In many cases of medication-induced macrocytosis, the red blood cell enlargement occurs without significant anemia.
Follow-Up Testing and Management
A high MCV requires careful follow-up to pinpoint the underlying cause. The diagnostic process begins with a detailed review of the person’s medical history, including diet, alcohol intake, and all current medications. A healthcare provider will then order specific blood tests to narrow down the possibilities.
Initial workup often includes checking serum levels of Vitamin B12 and folate to confirm or rule out nutritional causes. If these levels are normal, a comprehensive metabolic panel is usually ordered to assess liver function. A thyroid-stimulating hormone (TSH) test may also be included to check for underlying thyroid dysfunction.
A peripheral blood smear (review of the blood under a microscope) can provide visual clues, such as the shape of the enlarged cells or the presence of hypersegmented white blood cells. Management depends entirely on the final diagnosis. Treatment may range from simple dietary supplements for a vitamin deficiency to lifestyle changes or adjusting medication dosage under medical supervision.