From the Guidelines
The diagnostic workup for macrocytic anemia should begin with a complete blood count with peripheral smear, reticulocyte count, vitamin B12 level, folate level, thyroid function tests, liver function tests, and serum LDH, as these tests can help identify the underlying cause of the anemia, such as vitamin B12 or folate deficiency, which are common causes of macrocytic anemia 1. The initial evaluation should also include a thorough medical history, including alcohol use and medication review, as chronic alcoholism and certain medications, such as methotrexate and hydroxyurea, can cause macrocytosis 1. If the initial tests are inconclusive, additional tests, such as methylmalonic acid and homocysteine levels, may be necessary to rule out vitamin B12 deficiency, despite normal B12 levels 1. In some cases, bone marrow examination may be necessary to rule out myelodysplastic syndrome or other bone marrow disorders, which can also cause macrocytic anemia 1. Key points to consider in the diagnostic workup include:
- Vitamin B12 and folate levels to rule out deficiency
- Reticulocyte count to assess bone marrow response
- Thyroid function tests to rule out hypothyroidism
- Liver function tests to assess liver health
- Serum LDH to assess for hemolysis
- Medication review to identify potential causes of macrocytosis
- Bone marrow examination if initial tests are inconclusive or if myelodysplastic syndrome is suspected. Treatment of macrocytic anemia depends on the underlying cause, with vitamin B12 deficiency typically requiring intramuscular cyanocobalamin and folate deficiency requiring oral folate supplementation 1.
From the Research
Diagnostic Workup for Macrocytic Anemia
The diagnostic workup for macrocytic anemia involves several steps to determine the underlying cause of the condition. The following are some of the key components of the diagnostic workup:
- History and physical examination to identify potential causes such as alcoholism, liver disease, or hypothyroidism 2, 3
- Complete blood count (CBC) to confirm the presence of macrocytosis (mean corpuscular volume > 100 fL) 2, 4
- Peripheral smear to evaluate for megaloblastic or non-megaloblastic anemia 2, 3
- Reticulocyte count to help differentiate between causes such as drug or alcohol toxicity, hemolysis, or hemorrhage 2, 3
- Serum vitamin B12 and folate levels to evaluate for deficiencies 2, 3, 5
- Serum thyroid studies to evaluate for hypothyroidism 3
- Liver function studies to evaluate for liver disease 3
- Bone marrow aspirate and biopsy with cytogenetic analysis to evaluate for myelodysplasia or other bone marrow disorders 3, 6
Special Considerations
In some cases, additional testing may be necessary to confirm a diagnosis. For example:
- If megaloblastic anemia is suspected, a trial of vitamin B12 or folate supplementation may be necessary to confirm the diagnosis 6
- If myelodysplastic syndrome (MDS) is suspected, a hematology consultation may be appropriate 4
- If pernicious anemia is suspected, testing for anti-intrinsic factor antibodies may be necessary 6