The Mean Corpuscular Volume, or MCV, is a measurement included in a standard Complete Blood Count (CBC) that reflects the average size of red blood cells (RBCs). A high MCV value, typically defined as a measurement over 100 femtoliters (fL), indicates the presence of abnormally large red blood cells, a condition known as macrocytosis. These cells, called macrocytes, are often immature or abnormally formed, which can compromise their function. When red blood cells are too large, their ability to efficiently deliver oxygen may be impaired. Macrocytosis is not a diagnosis in itself, but rather a finding that signals an underlying issue affecting the production or maturation of these cells in the bone marrow.
Nutrient Deficiencies as Primary Causes
Deficiencies in certain B vitamins are among the most common reasons for an elevated MCV, specifically Vitamin B12 (cobalamin) and Folate (Vitamin B9). Both of these nutrients are necessary cofactors in DNA synthesis and cell division within the bone marrow, where red blood cells are produced. When one or both are lacking, the production process becomes faulty, leading to a type of anemia called megaloblastic anemia.
The developing red blood cell precursors cannot complete their cell division properly due to the impaired DNA synthesis, even though the cytoplasm continues to grow. This results in the release of oversized, immature cells (macro-ovalocytes) into the bloodstream, which is what the elevated MCV measures. Macrocytosis caused by these deficiencies is often associated with the most significant MCV elevations, sometimes reaching values between 116 and 130 fL.
A deficiency in Vitamin B12 can arise not only from low dietary intake, such as in strict vegan diets, but also from malabsorption issues. Conditions like pernicious anemia, where the body fails to produce the intrinsic factor required to absorb B12, can lead to severe B12 deficiency. Folate deficiency can be caused by poor diet, but it is also seen in conditions that increase the body’s folate requirement, or in intestinal disorders like celiac disease that hinder absorption.
Systemic and Medication-Related Causes
Causes of macrocytosis not related to B12 or folate deficiency are broadly categorized as non-megaloblastic and often involve systemic conditions or external factors. Chronic alcohol use is a frequent cause of high MCV because alcohol can directly interfere with the red blood cell membrane and impair the metabolism and absorption of folate.
Liver disease, such as cirrhosis, can also lead to an increased MCV by changing the composition of fats in the red blood cell membrane, causing the cells to swell. In cases of liver disease or alcohol-related macrocytosis, the red blood cells tend to be round macrocytes, which is a different visual characteristic than the oval-shaped cells seen in B12/folate deficiency. These systemic causes typically result in MCV elevations in a more moderate range, often between 100 and 116 fL.
Certain prescription medications can also contribute to an elevated MCV. Drugs used in chemotherapy, some antiviral medications used to treat HIV, and the drug hydroxyurea are known to interfere with DNA replication, mimicking the mechanism seen in B vitamin deficiencies. An underactive thyroid, known as hypothyroidism, is another systemic condition that can cause a high MCV, although the exact mechanism is not fully understood.
The Diagnostic Process Following High MCV
A high MCV reading serves as a preliminary indicator, necessitating a focused investigation to determine the root cause. Initial laboratory workup often includes:
- Measuring serum levels of Vitamin B12 and folate to confirm or rule out the most common nutritional causes.
- A Reticulocyte Count, which measures the number of immature red blood cells. An elevated count suggests the body is rapidly producing cells, often in response to blood loss or destruction (hemolysis), which artificially raises the MCV.
- Liver Function Tests (LFTs) and a Thyroid Stimulating Hormone (TSH) test to assess for liver disease or hypothyroidism.
- Reviewing a peripheral blood smear, which provides additional clues, such as the shape of the macrocytes (oval vs. round).
The full context of the Complete Blood Count, including whether the patient also has anemia or other low blood cell counts, guides the selection of further specialized testing.