From the Guidelines
Isolated mild elevation of Mean Corpuscular Volume (MCV) is most commonly caused by vitamin B12 or folate deficiency, as indicated by the European Consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases 1. The causes of isolated mild elevation of MCV can be multifactorial, including:
- Vitamin B12 or folate deficiency, which are essential for DNA synthesis during red blood cell production 1
- Alcohol abuse, which interferes with folate metabolism and directly affects red blood cell membrane formation
- Certain medications, such as thiopurine treatment (azathioprine or 6-mercaptopurine), anticonvulsants, methotrexate, and some antiretroviral drugs
- Liver disease, which affects red blood cell membrane composition, leading to macrocytosis
- Hypothyroidism, which slows down metabolism and can increase MCV values
- Myelodysplastic syndromes, though less common, cause ineffective hematopoiesis resulting in larger red cells
- Reticulocytosis (increased immature red cells) following blood loss or hemolysis can temporarily raise MCV since reticulocytes are larger than mature red cells According to the third European evidence-based consensus on diagnosis and management of ulcerative colitis, patients with mild MCV elevation should be evaluated for these causes through a detailed history focusing on alcohol use, medication review, and appropriate laboratory testing including B12, folate, liver function, and thyroid studies 1. The most appropriate initial step in evaluating isolated mild elevation of MCV is to assess for vitamin B12 or folate deficiency, as well as other potential causes, and address the underlying cause to normalize MCV values 1.
From the Research
Causes of Isolated Mild Elevation of Mean Corpuscular Volume (MCV)
- Vitamin B12 or folate deficiency is a common cause of macrocytosis, which can lead to an elevated MCV 2
- Liver disease can also cause mild and uniform macrocytosis, resulting in an elevated MCV 2
- Reticulocytosis can cause a mild elevation of MCV, but the MCV rarely exceeds 110 cu mu and a reticulocyte count can quickly establish the diagnosis 2
- Alcohol abuse is a common cause of macrocytosis, and can lead to an elevated MCV 3
- Hypothyroidism can also cause an elevated MCV 3
- Increased serum total homocysteine (tHcy) values are related to both increased erythrocyte mean cellular volume (MCV) and raised serum total homocysteine (tHcy) values, and may be a better indicator of vitamin B12 and folate status than serum levels of B12 and folate 4
Laboratory Investigations
- Serum vitamin B12 determination is the best test for unmasking vitamin B12 deficiency, and should be ordered in conjunction with serum and red cell folate determinations 2
- Reticulocyte parameters, such as MCVr, CHr, and CHCMr, can be useful in differentiating mixed anemia from vitamin B12 deficiency, IDA, and healthy controls 5
- A complete blood count (CBC) with RBC indices can help identify patients with macrocytosis, and further laboratory investigations can help determine the underlying cause 3