What is the treatment for pernicious anemia?

Treatment for Pernicious Anemia

The standard treatment for pernicious anemia is lifelong vitamin B12 replacement, with intramuscular (IM) cyanocobalamin as the recommended first-line therapy at a dose of 100 mcg daily for 6-7 days, followed by alternate day dosing for seven doses, then every 3-4 days for 2-3 weeks, and finally 100 mcg monthly for life. 1

Diagnosis and Initial Assessment

Before initiating treatment, confirm the diagnosis of pernicious anemia through:

• Complete blood count showing megaloblastic anemia
• Low serum vitamin B12 levels
• Presence of anti-intrinsic factor and/or anti-parietal cell antibodies
• Impaired vitamin B12 absorption correctable by administering intrinsic factor

Important: Neurologic disorders in pernicious anemia can occur even in the absence of anemia and macrocytosis, so a low serum cobalamin level should never be ignored, particularly in patients with neurologic symptoms. 2

Treatment Protocol

Intramuscular (IM) Vitamin B12 Replacement (First-line)

1. Initial Phase:

   • 100 mcg daily for 6-7 days via intramuscular or deep subcutaneous injection 1

2. Intermediate Phase:

   • If clinical improvement and reticulocyte response occur:
     • 100 mcg every other day for 7 doses
     • Then 100 mcg every 3-4 days for 2-3 weeks

3. Maintenance Phase:

   • 100 mcg monthly for life 1

Oral Vitamin B12 Replacement (Alternative)

Recent evidence suggests oral vitamin B12 can be effective despite the intrinsic factor deficiency that characterizes pernicious anemia:

• Dosage: 1000 μg (1 mg) daily 3, 4
• Efficacy: Studies show that 88.5% of patients were no longer deficient after 1 month of oral therapy 4
• Mechanism: Works through passive enteral absorption, bypassing the need for intrinsic factor

Important: Patients should be offered the oral alternative after an informed discussion about advantages and disadvantages of both treatment options. 3

Monitoring Response to Treatment

Laboratory Monitoring

• Check hemoglobin weekly until stable, then monthly 5
• Monitor vitamin B12 levels, homocysteine, and methylmalonic acid (MMA) concentrations
• With proper treatment, expect:
  • Normalization of hemoglobin and serum B12 within two months
  • Improvement in neurological symptoms within one month 6

Clinical Monitoring

• Assess for improvement in:
  • Hematologic parameters (anemia, macrocytosis)
  • Neurologic symptoms (tingling, numbness, ataxia)
  • Other symptoms (fatigue, weakness, depression)

Common Pitfalls to Avoid

1. Inadequate treatment duration: Pernicious anemia requires lifelong treatment; stopping therapy will result in recurrence of deficiency

2. Ignoring neurologic symptoms: Neurologic manifestations can occur even without anemia and may become permanent if treatment is delayed 7, 2

3. Using intravenous route: Avoid intravenous administration as most of the vitamin will be lost in urine 1

4. Failure to consider concomitant deficiencies: Assess and treat concurrent folate deficiency if present 1

5. Overlooking the need for regular monitoring: Even with proper initial treatment, patients need ongoing monitoring to ensure adequate vitamin B12 levels are maintained

Special Considerations

• For patients with normal intestinal absorption but vitamin B12 deficiency from other causes, oral B12 preparations may be sufficient for chronic treatment 1

• Patients with severe neurologic symptoms may benefit from more aggressive initial replacement therapy and closer monitoring 7

• Consider screening for other autoimmune conditions, as pernicious anemia is often associated with other autoimmune disorders such as thyroid disease and vitiligo 7