What are the steps to diagnose pernicious anemia?

Diagnosing Pernicious Anemia

The diagnosis of pernicious anemia requires a combination of laboratory tests including complete blood count with red cell indices, vitamin B12 levels, intrinsic factor antibodies, and parietal cell antibodies, with intrinsic factor antibodies being the most specific diagnostic marker (100% specificity). 1, 2

Initial Laboratory Evaluation

• Complete Blood Count (CBC) with Red Cell Indices:

  • Look for macrocytic anemia (MCV >100 fL) 3
  • Hemoglobin <13 g/dL in men or <12 g/dL in non-pregnant women 4
  • Elevated red cell distribution width (RDW) 3
  • Low reticulocyte count (indicating decreased RBC production) 3

• Vitamin B12 Level:

  • Low serum vitamin B12 (<200 pg/mL) is a key diagnostic finding 5
  • Note: Some patients may present with normal or even spuriously high B12 levels despite functional deficiency 2

Confirmatory Testing

• Autoantibody Testing:

  • Intrinsic factor antibodies (73% sensitivity, 100% specificity) 6
  • Parietal cell antibodies (present in 90% of cases) 6

• Additional Laboratory Tests:

  • Elevated serum homocysteine and methylmalonic acid levels (more sensitive markers of functional B12 deficiency) 1
  • Increased serum gastrin and decreased pepsinogen I (markers of atrophic gastritis) 6

Bone Marrow Examination

• Consider if diagnosis remains unclear or to rule out other causes of macrocytic anemia
• Look for megaloblastic changes in erythroid precursors 3
• May show ring sideroblasts which can cause diagnostic confusion 2

Gastroenterological Evaluation

• Upper Endoscopy with Gastric Biopsy:
  • To confirm atrophic body gastritis (ABG), the underlying pathology in pernicious anemia 6
  • Look for thinning of gastric mucosa and loss of parietal cells 6

Differential Diagnosis Considerations

1. Other Causes of Macrocytic Anemia:

   • Folate deficiency
   • Alcoholism
   • Myelodysplastic syndrome
   • Medication effects (e.g., hydroxyurea, diphenytoin) 3

2. Clinical Mimics:

   • Myelodysplastic syndrome
   • Acute leukemia
   • Bone marrow failure states
   • Thrombotic microangiopathy 5

3. Coexisting Conditions:

   • Iron deficiency (may mask macrocytosis)
   • Thalassemia
   • Autoimmune hemolytic anemia 2

Special Considerations

• Neurological Assessment:

  • Evaluate for peripheral neuropathy, ataxia, and other neurological manifestations 7
  • Neurological symptoms may occur even in the absence of anemia or macrocytosis 1

• Associated Autoimmune Disorders:

  • Screen for autoimmune thyroid disease (present in 40% of patients)
  • Consider other autoimmune conditions like diabetes mellitus (10%), vitiligo 7, 6

Common Diagnostic Pitfalls

• Relying solely on vitamin B12 levels without confirmatory testing 2
• Failure to recognize neurological manifestations in the absence of anemia 7
• Missing the diagnosis in patients with normal MCV due to coexisting microcytic anemia 1
• Not considering pernicious anemia in younger patients (15% of cases occur in younger individuals) 6

By following this systematic diagnostic approach, clinicians can accurately identify pernicious anemia and initiate appropriate vitamin B12 replacement therapy to prevent irreversible neurological complications.