What is the treatment for pernicious anemia?

Treatment of Pernicious Anemia

Lifelong vitamin B12 replacement is required for pernicious anemia, with intramuscular cyanocobalamin 100 mcg monthly being the FDA-approved standard treatment, though high-dose oral cyanocobalamin 1000 μg daily represents an effective alternative that should be offered to patients after informed discussion. 1, 2

Initial Treatment Phase

Intramuscular/subcutaneous route (FDA-approved regimen):

• Administer 100 mcg daily for 6-7 days by intramuscular or deep subcutaneous injection 1
• Continue with 100 mcg on alternate days for seven doses if clinical improvement and reticulocyte response are observed 1
• Follow with 100 mcg every 3-4 days for another 2-3 weeks until hematologic values normalize 1
• Avoid intravenous administration as almost all vitamin will be lost in urine 1

Oral route (alternative):

• Oral cyanocobalamin 1000 μg daily can be initiated as primary therapy 2, 3
• Within 1 month, 88.5% of patients achieve vitamin B12 sufficiency with significant improvement in plasma B12, homocysteine, and methylmalonic acid levels 3
• Serum cobalamin concentrations normalize (>200 pg/mL) in the majority of patients within 3 months 4

Maintenance Treatment

Standard maintenance:

• Intramuscular cyanocobalamin 100 mcg monthly for life 1
• Oral cyanocobalamin 1000 μg daily for life if oral route is chosen 2, 3

Concomitant supplementation:

• Administer folic acid concomitantly if folate deficiency is present 1
• Evaluate and treat iron deficiency, which commonly coexists with pernicious anemia 5

Monitoring Requirements

Laboratory monitoring:

• Regular vitamin B12 levels and complete blood count for long-term monitoring 5
• Hemoglobin typically increases by 2.5 g/dL within 3 months of treatment 4
• Mean corpuscular volume decreases by approximately 10 fL within 3 months 4

Clinical monitoring timeline:

• Hemolysis reverses within 1 month 3
• Mucosal symptoms improve within 4 months 3
• Neurologic symptoms (paresthesia, reflex abnormalities, combined medullary sclerosis) may improve, though some sequelae can become irreversible if treatment is delayed 6, 4

Surveillance and Associated Conditions

Endoscopic surveillance:

• Initial endoscopy with topographical biopsies is recommended to confirm corpus-predominant atrophic gastritis and rule out gastric neoplasia including neuroendocrine tumors 5
• Endoscopic surveillance every 3 years is recommended due to approximately three times higher risk of gastric cancer compared to the general population 5

Screen for autoimmune comorbidities:

• Screen for autoimmune thyroid disease, which commonly coexists with pernicious anemia 5
• Evaluate for other autoimmune disorders as clinically indicated 5

Critical Pitfalls to Avoid

Diagnostic challenges:

• Hematologic variables may be normal in patients with cobalamin deficiency, so do not rely solely on complete blood count 7
• Urinary methylmalonic acid measurement is more sensitive than serum B12 alone for detecting deficiency 7
• Schilling test results should be interpreted cautiously and are not routinely necessary for diagnosis 7

Treatment considerations:

• Prompt recognition and treatment is vital because neurologic sequelae may become irreversible despite vitamin B12 replacement 6
• Oral vitamin B12 works through passive enteral absorption (1-2% absorption rate), requiring high doses to bypass intrinsic factor deficiency 2
• When offering oral therapy, discuss that it requires daily adherence versus monthly injections, but avoids injection-related discomfort 2