What labs are used to diagnose pernicious anemia?

Laboratory Tests for Diagnosing Pernicious Anemia

The diagnosis of pernicious anemia requires a combination of complete blood count, vitamin B12 levels, and autoantibody testing, specifically anti-intrinsic factor antibodies and anti-parietal cell antibodies. 1

Primary Diagnostic Tests

Hematologic Parameters

• Complete blood count (CBC)
  • Macrocytic anemia (elevated mean corpuscular volume [MCV])
  • Low hemoglobin and hematocrit
  • Possible pancytopenia in severe cases 1
• Peripheral blood smear
  • Hypersegmented neutrophils
  • Macro-ovalocytes
  • Anisocytosis and poikilocytosis 1, 2

Vitamin B12 Status

• Serum vitamin B12 levels
  • Low levels (<200 pg/mL) strongly suggest deficiency
  • Note: Normal B12 levels don't exclude functional deficiency 1
• Methylmalonic acid (MMA)
  • Elevated in vitamin B12 deficiency
  • More sensitive marker than serum B12 alone 1
• Homocysteine levels
  • Elevated in both B12 and folate deficiency
  • Helps differentiate from isolated folate deficiency when used with MMA 1

Autoimmune Markers

• Anti-intrinsic factor antibodies (anti-IFAB)
  • High specificity (98.6%) for pernicious anemia
  • Moderate sensitivity (40.9%)
  • Positive result strongly confirms diagnosis 1, 3
• Anti-parietal cell antibodies (anti-PCA)
  • Higher sensitivity (68.2%) but lower specificity (91.7%)
  • Excellent screening test for pernicious anemia 3, 4

Confirmatory Testing

Gastric Assessment

• Upper endoscopy with gastric biopsies
  • Confirms presence of atrophic gastritis
  • Rules out other causes of B12 deficiency
  • Should be performed in newly diagnosed pernicious anemia 1
• Histopathological examination
  • Corpus-predominant atrophic gastritis
  • Intestinal metaplasia
  • Possible neuroendocrine tumors 1

Additional Tests

• Iron studies
  • Ferritin, transferrin saturation
  • Concurrent iron deficiency is common 1, 2
• Folate levels
  • To rule out concurrent folate deficiency 1
• Screening for associated autoimmune disorders
  • Thyroid function tests (autoimmune thyroid disease commonly coexists) 1

Diagnostic Algorithm

1. Initial screening:

   • CBC showing macrocytic anemia
   • Low serum vitamin B12 levels

2. Confirmatory testing:

   • Anti-parietal cell antibodies (screening test)
   • Anti-intrinsic factor antibodies (confirmatory test)
   • MMA and homocysteine levels if B12 levels are borderline

3. Endoscopic evaluation:

   • Upper endoscopy with biopsies to confirm atrophic gastritis
   • Rule out gastric neoplasia, including neuroendocrine tumors

4. Associated testing:

   • Screening for concurrent autoimmune disorders, particularly thyroid disease

Clinical Pearls and Pitfalls

• Combined antibody testing: Using both anti-intrinsic factor and anti-parietal cell antibody tests increases diagnostic sensitivity to 86.4% 3

• Pitfall: Relying solely on serum B12 levels can miss functional B12 deficiency; MMA is more sensitive 1, 5

• Pitfall: Testing for intrinsic factor antibodies alone without parietal cell antibodies has limited value - only 0.47% of patients are positive for intrinsic factor antibodies alone 4

• Caution: Neurological symptoms may precede hematological abnormalities; don't dismiss B12 deficiency in patients with normal CBC but neurological symptoms 6

• Important: All patients with newly diagnosed pernicious anemia should undergo endoscopy to confirm corpus-predominant atrophic gastritis and rule out gastric neoplasia 1

By following this comprehensive diagnostic approach, pernicious anemia can be accurately diagnosed, allowing for appropriate vitamin B12 replacement therapy and monitoring for associated conditions.