From the Guidelines
For macrocytic anemia, the essential lab tests include vitamin B12 and folate levels, as these directly assess the most common causes of the condition, and should be measured at least once at first assessment and repeated within 3 months after supplementation to verify normalization, as recommended by the espen micronutrient guideline 1. When investigating macrocytic anemia, it is crucial to identify the underlying cause, and measuring folic acid status, along with B12, is a key step in this process.
- The initial assessment should include a complete blood count (CBC) with peripheral smear to confirm anemia and reveal the elevated mean corpuscular volume (MCV >100 fL) characteristic of macrocytic anemia.
- Vitamin B12 and folate levels are essential, as they are the most common causes of macrocytic anemia, and the espen micronutrient guideline recommends measuring these at least once at first assessment and repeated within 3 months after supplementation to verify normalization 1.
- Additional tests, such as thyroid function tests, liver function tests, reticulocyte count, and serum LDH, may be necessary to identify other potential causes of macrocytosis, such as hypothyroidism or liver disease.
- While other studies, such as the myelodysplastic syndromes clinical practice guidelines, recommend a range of tests, including bone marrow aspiration and cytogenetics 1, these are not universally necessary for the initial investigation of macrocytic anemia, and the most recent and highest quality evidence supports the measurement of vitamin B12 and folate levels as the primary initial step 1.
From the Research
Lab Tests for Macrocytic Anemia
To diagnose and determine the underlying cause of macrocytic anemia, several lab tests can be utilized. These include:
- Complete Blood Count (CBC) to determine the mean corpuscular volume (MCV) and identify macrocytosis 2, 3, 4, 5
- Vitamin B12 level to check for deficiency, a common cause of megaloblastic anemia 2, 3, 4, 5
- Reticulocyte count to help differentiate between causes of macrocytosis, such as drug or alcohol toxicity, hemolysis, or hemorrhage 2, 3
- Peripheral smear to examine the morphology of red blood cells and identify characteristics such as macro-ovalocytes and hyper-segmented neutrophils, indicative of megaloblastic anemia 2, 3
- Red blood cell folate level to check for folate deficiency, another cause of megaloblastic anemia 3, 4, 5
- Thyroid function tests to check for hypothyroidism, a potential cause of nonmegaloblastic macrocytic anemia 3, 5
- Liver function tests to check for liver disease, which can cause nonmegaloblastic macrocytic anemia 3, 4, 5
- Schilling test to determine if vitamin B12 can be absorbed and if intrinsic factor corrects malabsorption 3, 4
Additional Tests
In some cases, additional tests may be necessary to determine the underlying cause of macrocytic anemia, such as:
- Bone marrow studies, although not typically indicated for initial evaluation 4
- Plasma uptake test to pinpoint the cause of vitamin B12 deficiency 4
- Hematology consultation if myelodysplastic syndrome (MDS) is suspected, particularly in elderly patients with leukocytopenia and/or thrombocytopenia with anemia 5