Macrocytic Anemia: Diagnosis and Treatment
This patient has macrocytic anemia (MCV 99.1, Hb 10.2, Hct 31.0) and requires immediate evaluation for vitamin B12 and folate deficiency, followed by assessment for other causes including liver disease, hypothyroidism, and bone marrow disorders. 1
Immediate Diagnostic Workup
The following tests must be ordered before initiating any treatment:
- Vitamin B12 and folate levels - These are essential first-line tests as deficiency of either can present with macrocytic anemia, and serum B12 determination remains the best test for unmasking B12 deficiency 1, 2
- Reticulocyte count - Critical to distinguish between production defects (low/normal reticulocytes) versus hemolysis or acute blood loss (elevated reticulocytes) 1, 3
- Iron studies (serum ferritin and transferrin saturation) - Necessary to exclude concurrent iron deficiency, with ferritin <30 μg/L indicating deficiency in the absence of inflammation 1
- Peripheral blood smear - Look for oval macrocytes (suggesting megaloblastic anemia where MCV may exceed 150 fL) versus round macrocytes (suggesting liver disease with mild, uniform macrocytosis and MCV rarely exceeding 110 fL) 1, 2
- Thyroid function tests and liver function tests - To evaluate for hypothyroidism and liver disease as causes of macrocytosis 1
Critical Diagnostic Pitfall
Do not rely on MCV alone to guide your differential diagnosis. A recent study found that in 90% of macrocytic patients, the actual anemia etiology did not match what would be predicted by MCV-guided classification alone 4. This means you must order a comprehensive panel regardless of the MCV value.
Treatment Based on Etiology
If Vitamin B12 Deficiency is Confirmed:
- Initiate intramuscular vitamin B12 (cyanocobalamin) immediately - Patients with pernicious anemia require monthly injections for life 5
- Monitor closely during initial treatment - Serum potassium must be observed in the first 48 hours and replaced if necessary 5
- Track response - Hematocrit and reticulocyte counts should be repeated daily from days 5-7 of therapy, then frequently until hematocrit normalizes 5
- Warning: Vitamin B12 deficiency allowed to progress for longer than 3 months may produce permanent degenerative lesions of the spinal cord 5
- Never substitute folic acid for B12 - Doses of folic acid >0.1 mg/day may produce hematologic remission but will not prevent irreversible neurologic damage 5
If Folate Deficiency is Identified:
- Administer folic acid supplementation, but only after confirming B12 levels are adequate or being treated concurrently 5
If No Nutritional Deficiency is Found:
- Evaluate for chronic disease, renal dysfunction, liver disease, hypothyroidism, or medication effects 1, 6
- Consider hematology referral if abnormalities in multiple cell lines are present or if there is lack of response to appropriate therapy 1
Monitoring Treatment Response
If reticulocytes have not increased after treatment, or if reticulocyte counts do not continue at least twice normal while hematocrit remains <35%, the diagnosis or treatment must be reevaluated 5. Repeat iron and folate determinations may reveal a complicating illness inhibiting marrow response 5.
Special Consideration for Pernicious Anemia
Patients with pernicious anemia have approximately 3 times the incidence of gastric carcinoma compared to the general population, so appropriate screening should be performed when indicated 5.