The Mean Corpuscular Volume (MCV) is a measurement included in a routine Complete Blood Count (CBC), used to assess overall health. A high MCV indicates the average size of red blood cells is larger than normal. While this finding can prompt concern about serious underlying conditions, it is far more frequently a sign of common and treatable non-cancerous issues. The significance of this single blood marker is determined only after a full review of the entire blood profile and the patient’s comprehensive medical history.
Understanding Mean Corpuscular Volume
The MCV is a laboratory value that measures the average volume of a red blood cell, expressed in femtoliters (fL). Red blood cells are produced in the bone marrow and transport oxygen throughout the body. The typical normal range for an adult MCV is between 80 and 100 fL.
An MCV reading above this limit is known as macrocytosis, indicating the presence of abnormally large red cells. Macrocytosis is a descriptive finding that points toward a problem with how these cells are being produced or how their membranes are structured. This size change often occurs because red blood cell precursors in the bone marrow are unable to divide properly during maturation.
Common Non-Malignant Causes of Elevated MCV
The most common reasons for macrocytosis involve deficiencies in Vitamin B12 and folate. Both nutrients are necessary cofactors for DNA synthesis, required for cells to divide accurately in the bone marrow. When these vitamins are lacking, red blood cell precursors grow larger without successfully dividing, resulting in fewer but oversized cells—a condition known as megaloblastic change.
Chronic, heavy alcohol consumption is another frequent cause of an elevated MCV, often through multiple mechanisms. Alcohol directly interferes with the bone marrow’s ability to produce normal cells and often leads to poor nutrition and subsequent folate deficiency. Furthermore, chronic liver disease, whether alcohol-related or not, can cause macrocytosis. This occurs because changes in lipid metabolism lead to the deposition of cholesterol and fats on the red blood cell membranes, making the cells swell and appear larger.
Common medications can also cause macrocytosis by interfering with cell division. For example, certain anticonvulsant drugs like phenytoin and valproic acid impact folate metabolism, while the diabetes medication metformin can impair Vitamin B12 absorption. Other culprits include methotrexate, a folate antagonist, and hydroxyurea, which directly affects DNA synthesis. Finally, a temporary MCV increase can occur after significant blood loss or hemolysis because the body releases reticulocytes, which are immature red blood cells naturally larger than mature cells.
When High MCV Relates to Cancer
While most cases of high MCV are not cancer-related, the measurement can be a direct or indirect sign of certain malignancies. The most significant direct link is to Myelodysplastic Syndromes (MDS), a group of blood cancers. MDS is a disorder where defective blood-forming stem cells in the bone marrow lead to ineffective hematopoiesis and the production of large, poorly formed cells.
In MDS, macrocytosis is a manifestation of this dysplasia and is frequently accompanied by low counts of other blood components, such as white blood cells and platelets—a finding known as pancytopenia. Acute Myeloid Leukemia (AML) can also present with macrocytosis, particularly if it arises from pre-existing MDS. Both conditions involve the production of large, immature myeloid blast cells, reflecting a fundamental problem with the bone marrow’s cellular maturation process.
An indirect link involves malignancies of the gastrointestinal tract. Stomach cancer, for instance, can destroy the cells responsible for producing intrinsic factor, a protein necessary for B12 absorption. This malabsorption leads to a severe B12 deficiency, which then causes macrocytosis. Similarly, pancreatic cancers can affect the enzymes needed for B12 release from food, resulting in deficiency. In these scenarios, the high MCV is caused not by the cancer cells themselves, but by the tumor’s effect on nutrient absorption.
Interpreting Elevated Results and Next Steps
An isolated high MCV result should prompt a structured investigation rather than immediate alarm. Since the causes are varied, a physician uses the complete clinical picture to determine the next steps. The first line of testing typically includes measuring serum levels of Vitamin B12 and folate to check for common deficiencies.
If these results are inconclusive, specialized metabolites like methylmalonic acid and homocysteine may be measured, as their elevation helps pinpoint a B12 deficiency at a cellular level. Further tests often include liver function panels and thyroid-stimulating hormone (TSH) to rule out liver disease and hypothyroidism. A detailed review of all current medications is also performed to identify drug-induced causes.
The doctor will often order a peripheral blood smear, which involves examining the blood under a microscope to assess the size and shape of the red blood cells and look for abnormal or immature cells. If macrocytosis is severe or accompanied by other unexplained low blood counts, a bone marrow examination may be necessary to directly assess for MDS or other primary bone marrow disorders. The MCV is treated as an initial flag, requiring comprehensive follow-up testing to arrive at a definitive diagnosis.