Key Takeaways

✅ The differential diagnosis of macrocytosis includes elevated reticulocyte count, vitamin B12 deficiency, folate deficiency, alcohol, liver disease, hypothyroidism, medications, and primary bone marrow processes such as plasma cell dyscrasia, aplastic anemia and myelodysplastic syndrome.

✅ The first step in working up a patient with macrocytosis (aside from examining a peripheral smear) is to rule out reticulocytosis, which may occur in the setting of acute bleeding or hemolysis.

✅ The peripheral smear can give important clues about the cause of macrocytosis. In the case of suspected vitamin B12 deficiency, look for macro-ovalocytes and hypersegmented neutrophils. Severe deficiency may be associated with a disorganized smear, including the presence of schistocytes.

✅ Vitamin B12 deficiency is diagnosed using serum levels of vitamin B12, though functional assays, especially methylamalonic acid levels, may detect cases with otherwise normal vitamin B12 levels.

✅ Pernicious anemia is the most common cause of vitamin B12 deficiency (about 50% of cases). Diagnosis requires demonstration of anti-intrinsic factor antibodies (though these are not 100% sensitive) +/- stomach biopsy.

✅ Pernicious anemia may be considered:

• A gastrointestinal disorder because the proximate cause is immune-mediated destruction of parietal cells in the stomach.
• A hematological disorder because reduced vitamin B12 levels may lead to megaloblastic anemia.
• A neurological condition because reduced vitamin B12 levels may lead to a demyelinating syndrome.