How is pernicious anemia diagnosed?

Diagnosing Pernicious Anemia

Pernicious anemia should be diagnosed through a combination of hematologic testing, vitamin B12 levels, autoantibody testing, and in some cases, gastric evaluation to confirm intrinsic factor deficiency.

Initial Laboratory Evaluation

• Complete blood count (CBC):

  • Macrocytic anemia (elevated MCV) is characteristic 1
  • Hemoglobin below normal range (typically <12 g/dL in women, <13 g/dL in men) 2
  • Elevated red cell distribution width (RDW) may be present 2

• Vitamin B12 levels:

  • Serum vitamin B12 level is typically low (<200 pg/mL) 1
  • Note: Normal vitamin B12 levels do not rule out functional deficiency

• Iron studies:

  • To exclude concurrent iron deficiency which may mask macrocytosis 3
  • Include serum ferritin, transferrin saturation, serum iron

Confirmatory Testing

• Autoantibody testing:

  • Anti-intrinsic factor antibodies (73% sensitivity, 100% specificity) 4
  • Anti-parietal cell antibodies (present in 90% of cases) 4

• Metabolic markers:

  • Elevated methylmalonic acid (MMA) - more sensitive than serum B12 5
  • Elevated homocysteine levels

• Gastric evaluation:

  • Endoscopic confirmation of atrophic gastritis 4
  • Histological confirmation of gastric body atrophy

Diagnostic Algorithm

1. First step: CBC with peripheral blood smear showing macrocytic anemia and hypersegmented neutrophils
2. Second step: Low serum vitamin B12 level
3. Third step: Positive anti-intrinsic factor and/or anti-parietal cell antibodies
4. Fourth step (if needed): Elevated methylmalonic acid and homocysteine levels
5. Fifth step (if needed): Gastric biopsy showing atrophic gastritis

Neurological Assessment

• Evaluate for neurological manifestations:
  • Peripheral neuropathy (tingling, numbness)
  • Ataxia
  • Decreased proprioception
  • Impaired vibration sense
  • Hyperreflexia 6

Diagnostic Pitfalls to Avoid

• False normal B12 levels: Serum B12 may be normal despite tissue deficiency; methylmalonic acid testing is more sensitive 5
• Masking by folic acid: High-dose folic acid can mask hematologic manifestations while neurological damage progresses 7
• Concurrent iron deficiency: Can mask macrocytosis of B12 deficiency 3
• Misdiagnosis as thrombotic microangiopathy: Severe B12 deficiency can mimic thrombotic thrombocytopenic purpura 8
• Missing associated autoimmune conditions: Check for thyroid disease, diabetes, and other autoimmune disorders 4

Response to Treatment as Diagnostic Confirmation

• A robust response to vitamin B12 therapy (Hb increase ≥10 g/L within 2 weeks) strongly supports the diagnosis 3
• Neurological symptoms may improve more slowly or be irreversible if treatment is delayed 7

Important Considerations

• Pernicious anemia is the end-stage of autoimmune atrophic gastritis 4
• Patients require lifelong vitamin B12 replacement therapy 7
• Regular monitoring is essential as these patients have increased risk of gastric cancer 4
• Younger patients represent about 15% of pernicious anemia cases, so age should not exclude diagnosis 4

Prompt diagnosis and treatment are critical as neurological damage can become irreversible if vitamin B12 deficiency persists for more than 3 months 7, 1.