How to evaluate a patient with macrocytosis (Mean Corpuscular Volume (MCV) > 100)?

From the Guidelines

Evaluation of a patient with macrocytosis (MCV > 100) should begin with a thorough history and physical examination, focusing on alcohol use, medication review, dietary habits, and family history. Initial laboratory testing should include a complete blood count with peripheral smear, reticulocyte count, vitamin B12 and folate levels, thyroid function tests, liver function tests, and serum creatinine, as recommended by the most recent guidelines 1. The peripheral smear is particularly important as it can reveal hypersegmented neutrophils (suggesting B12/folate deficiency), target cells, or other abnormalities. If B12 deficiency is identified (levels <200 pg/mL), additional testing for intrinsic factor antibodies, parietal cell antibodies, and methylmalonic acid levels should be considered. For patients with alcoholism, abstinence should be recommended and thiamine supplementation initiated. Medication-induced macrocytosis requires consideration of drug discontinuation when possible. In cases where initial testing is inconclusive, bone marrow examination may be necessary to rule out myelodysplastic syndrome or other hematologic disorders. Some key points to consider in the evaluation of macrocytosis include:

• The distinction between iron deficiency anemia and anemia of chronic disease, which is important for treatment decisions 1
• The potential for macrocytosis to be a marker of serious conditions, including malignancy, liver disease, or nutritional deficiencies 1
• The importance of a thorough history and physical examination in identifying potential causes of macrocytosis, such as alcohol use or medication side effects 1
• The role of laboratory testing, including complete blood count, reticulocyte count, and vitamin B12 and folate levels, in evaluating macrocytosis 1

From the Research

Evaluation of Macrocytosis

To evaluate a patient with macrocytosis (Mean Corpuscular Volume (MCV) > 100), the following steps can be taken:

• History and physical examination to identify potential causes such as alcoholism, vitamin B12 and folate deficiencies, and medications 2
• Laboratory tests, including:
  • Vitamin B12 level to check for deficiency 2, 3, 4
  • Reticulocyte count to differentiate between drug or alcohol toxicity and hemolysis or hemorrhage 2, 5
  • Peripheral smear to check for megaloblastic anemia (macro-ovalocytes and hyper-segmented neutrophils) 2, 6, 4
• Other possible etiologies to consider:
  • Hypothyroidism 2, 6, 5
  • Liver disease 2, 6, 4
  • Primary bone marrow dysplasias (including myelodysplasia and myeloproliferative disorders) 2
  • Hemolysis or hemorrhage 2, 5
  • Drug effect 6

Diagnostic Approach

The diagnostic approach to macrocytosis involves a combination of laboratory tests and physical examination to identify the underlying cause.

• The combination of a low red cell count, high red cell distribution width, normal thrombocyte count, and normal thrombocyte mean cell volume can help differentiate between vitamin B12 deficiency and alcohol abuse 3
• Serum B12 vitamin measurement is recommended in patients with nonanemic macrocytosis, especially when combined with a low red cell count or high red cell distribution width 3
• A Schilling test or plasma uptake test may be indicated to pinpoint the cause of vitamin B12 deficiency 4