Workup for Pernicious Anemia
The comprehensive workup for pernicious anemia should include complete blood count with red cell indices, reticulocyte count, serum vitamin B12 levels, methylmalonic acid (MMA), homocysteine, serum ferritin, transferrin saturation, and testing for anti-intrinsic factor and anti-parietal cell antibodies. 1
Initial Laboratory Assessment
- Complete blood count (CBC) with red cell indices is essential to identify macrocytic anemia (MCV >100 fL), which is characteristic of vitamin B12 deficiency 2, 1
- Reticulocyte count should be measured to assess bone marrow response - typically low or normal in pernicious anemia 1
- Red cell distribution width (RDW) is often elevated (>15%) in vitamin B12 deficiency 3
- Peripheral blood smear examination to look for hypersegmented neutrophils and macrocytic red blood cells 4
Vitamin B12 Status Assessment
- Serum vitamin B12 level measurement is the first-line test, with levels <200 pg/mL strongly suggesting deficiency 1
- Methylmalonic acid (MMA) and homocysteine levels should be measured, as they are more sensitive markers of functional B12 deficiency and may be elevated even when serum B12 levels are in the low-normal range 2, 1
- Holotranscobalamin (holoTC) measurement, if available, has greater sensitivity than serum cobalamin for detecting B12 deficiency 2
Diagnostic Testing for Pernicious Anemia
- Anti-intrinsic factor antibodies - highly specific (>95%) for pernicious anemia 5, 4
- Anti-parietal cell antibodies - sensitive but less specific for pernicious anemia 5, 4
- Upper endoscopy with gastric biopsy to identify chronic atrophic gastritis, which is characteristic of pernicious anemia 4
- Schilling test (if available) to confirm malabsorption of vitamin B12 due to intrinsic factor deficiency 6
Additional Testing
- Serum folate levels should be measured, as folate deficiency can mask or coexist with B12 deficiency 6
- Iron studies (serum ferritin, transferrin saturation) to rule out concurrent iron deficiency 2
- Thyroid function tests to rule out hypothyroidism, which can present with similar symptoms 7
- Consider testing for other autoimmune conditions that may coexist with pernicious anemia (e.g., thyroid disorders, vitiligo) 7
Monitoring After Diagnosis
- After initiating treatment, monitor hematocrit and reticulocyte counts daily from the fifth to seventh days of therapy until hematocrit normalizes 6
- Serum potassium must be closely observed during the first 48 hours of treatment and replaced if necessary 6
- Regular monitoring of vitamin B12 levels, complete blood count, and neurological symptoms is necessary for patients on replacement therapy 6
- Patients with pernicious anemia have approximately three times the risk of gastric carcinoma compared to the general population, so appropriate surveillance should be considered 6
Important Clinical Considerations
- Neurological symptoms may precede hematological abnormalities in about one-third of cases, so absence of anemia does not rule out B12 deficiency 2, 7
- High-dose folic acid supplementation may mask the hematological manifestations of B12 deficiency while allowing neurological damage to progress 6
- Patients with pernicious anemia require lifelong vitamin B12 replacement, traditionally given as monthly intramuscular injections, though high-dose oral supplementation (1000 μg daily) may be effective in many patients 8, 5
- Untreated vitamin B12 deficiency that progresses beyond 3 months may lead to permanent neurological damage 6
By following this comprehensive diagnostic approach, clinicians can accurately diagnose pernicious anemia and initiate appropriate treatment to prevent irreversible neurological complications.