The Mean Corpuscular Volume (MCV) test, included in a routine Complete Blood Count (CBC), quantifies the average size of red blood cells. Red blood cells transport oxygen throughout the body. An elevated MCV, known as macrocytosis, signifies that the red blood cells are larger than normal. Identifying the reason for this enlargement is important, as a high MCV frequently points to underlying nutritional or health issues.
Defining Macrocytosis and Its Significance
Macrocytosis is defined as an MCV measurement greater than 100 femtoliters (fL) in adults; the normal range is typically 80 to 100 fL. Abnormally large cells suggest that red blood cell production (erythropoiesis) is impaired.
The size reflects the cell’s ability to divide and mature effectively. Larger-than-normal cells may not function efficiently and can break down prematurely, potentially leading to macrocytic anemia. Even without anemia, macrocytosis indicates cellular stress or dysfunction that requires investigation.
The Primary Nutritional and Lifestyle Causes
The most frequent causes of an elevated MCV fall into two major categories: nutritional deficiencies and chronic alcohol consumption. A deficiency in Vitamin B12 or Folate is the most common nutritional reason for macrocytic anemia. These two B vitamins are fundamental cofactors necessary for the synthesis of DNA within the developing red blood cells.
A shortage of either B12 or Folate disrupts DNA production, causing the red blood cells in the bone marrow to grow larger as their cytoplasm matures faster than their nucleus. This leads to the formation of large, immature cells called megaloblasts, a hallmark of megaloblastic anemia. The resulting macrocytes are typically oval-shaped and often appear alongside hypersegmented neutrophils, which reflect the same underlying DNA synthesis defect.
Chronic, heavy alcohol use is another widespread cause of a high MCV. Alcohol can cause macrocytosis through several mechanisms, including interference with the absorption of folate, which leads to a secondary nutritional deficit. Alcohol also exerts a direct toxic effect on the bone marrow, disrupting red blood cell development regardless of vitamin status.
This direct toxicity generally results in non-megaloblastic macrocytosis, where the large red blood cells are round rather than oval and do not show the characteristic nuclear abnormalities. This macrocytosis typically resolves only after several months of continuous abstinence. The combined effects of poor nutrition and direct bone marrow toxicity make alcohol use a dominant factor in high MCV cases.
Other Underlying Medical Conditions
Beyond the most common causes, several other medical conditions can lead to an elevated MCV. Severe liver dysfunction is a recognized cause of macrocytosis. Liver disease alters the metabolism of lipids, leading to an abnormal deposition of cholesterol and phospholipids onto the red blood cell membranes, which causes the cells to swell and become larger.
An underactive thyroid gland, or hypothyroidism, is also associated with macrocytosis. The link is not fully understood, but low thyroid hormone levels can affect cell metabolism and potentially lead to macrocytosis. Certain medications are known to interfere with red blood cell production or metabolism, causing an increase in MCV.
Chemotherapy agents (including methotrexate and hydroxyurea) and some antiretroviral drugs used for HIV treatment can directly impact the bone marrow. These medications often inhibit DNA synthesis, mimicking the mechanism of B12 or folate deficiency. Finally, primary bone marrow disorders, such as Myelodysplastic Syndromes (MDS), are serious but less common causes, where the bone marrow itself produces abnormal, large red blood cells due to a defect in stem cell function.
How Doctors Investigate High MCV
When a high MCV is detected, a physician initiates a diagnostic workup. The first step is a detailed review of the patient’s medical history, diet, and alcohol consumption, as these factors account for the majority of cases. Initial laboratory investigation focuses on measuring serum levels of Vitamin B12 and folate to check for nutritional deficiencies.
Further blood tests often include liver function tests (LFTs) and Thyroid-Stimulating Hormone (TSH) to screen for liver disease and hypothyroidism. To differentiate B12 and folate deficiency, doctors may order tests for methylmalonic acid (MMA) and homocysteine, since B12 deficiency specifically raises MMA levels. A peripheral blood smear is also performed to visually examine the size and shape of the red blood cells, distinguishing between megaloblastic (oval macrocytes) and non-megaloblastic (round macrocytes) causes.