From the Guidelines
An elevated MCV of 104.0 with normal B12 and thyroid function can most likely be caused by folate deficiency, certain medications, or reticulocytosis from hemolysis or recent blood loss, as indicated by the European Consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases 1. When considering the potential causes of an elevated MCV, it is essential to rule out common conditions such as iron deficiency anemia, which can be detected by measuring serum ferritin levels and transferrin saturation, as recommended in the European Consensus 1. Some key points to consider in the diagnosis include:
- Folate deficiency as a potential cause of macrocytosis, even with normal B12 levels
- Certain medications, such as anticonvulsants, methotrexate, and some HIV medications, which can cause an elevated MCV, as noted in the British Association of Dermatologists' guidelines for the safe and effective prescribing of methotrexate for skin disease 2016 1
- Reticulocytosis from hemolysis or recent blood loss, which can also lead to an elevated MCV
- The importance of a thorough history, including alcohol consumption and medication review, in determining the underlying cause of the elevated MCV
- Additional testing, such as a complete blood count with peripheral smear, liver function tests, and folate levels, to help determine the exact cause of the elevated MCV. Given the potential complexity of diagnosing the cause of an elevated MCV, it is crucial to prioritize a thorough diagnostic workup, including a detailed patient history and additional laboratory tests, to ensure accurate diagnosis and effective management, as emphasized in the European Consensus 1.
From the FDA Drug Label
Except during pregnancy and lactation, folic acid should not be given in therapeutic doses greater than 0.4 mg daily until pernicious anemia has been ruled out. The cause of a Mean Corpuscular Volume (MCV) of 104.0 when serum B12 is normal and thyroid tests are normal can be:
- Folic acid supplementation, as high doses of folic acid can mask vitamin B12 deficiency and lead to neurologic manifestations, but may not directly cause an elevated MCV in this context, however, it is essential to rule out pernicious anemia before giving therapeutic doses of folic acid 2. However, the provided text does not directly answer what causes the elevated MCV.
From the Research
Possible Causes of Elevated MCV
- Alcoholism: Studies have shown that alcoholism is a common cause of macrocytosis, with or without folate deficiency 3, 4, 5, 6, 7.
- Folate deficiency: Folate deficiency can cause macrocytosis, and it is often seen in patients with alcohol use disorder 4, 6, 7.
- Medications: Certain medications can cause macrocytosis, although the specific medications are not listed in the provided studies 3.
- Liver disease: Liver disease, particularly alcohol-related liver disease, can cause macrocytosis 5, 6, 7.
- Hemolysis or hemorrhage: Hemolysis or hemorrhage can cause macrocytosis, particularly if the peripheral smear is non-megaloblastic 3.
- Primary bone marrow dysplasias: Primary bone marrow dysplasias, including myelodysplasia and myeloproliferative disorders, can cause macrocytosis 3.
Relationship Between MCV and Folate Deficiency
- Macrocytosis can occur in the absence of folate deficiency, emphasizing the direct toxic effect of alcohol on the developing erythroblast 7.
- Folate deficiency is relatively frequent in patients with alcohol use disorder, and macrocytosis is significantly associated with folate deficiency 6.
Diagnostic Considerations
- A peripheral smear can help differentiate between megaloblastic and non-megaloblastic anemia, which can guide further diagnostic testing 3.
- Reticulocyte count can help differentiate between drug or alcohol toxicity and hemolysis or hemorrhage 3.
- Serum folate levels can be used to diagnose folate deficiency, but may not always be abnormal in patients with macrocytosis 6, 7.