Management of Pernicious Anemia
Lifelong intramuscular vitamin B12 (cyanocobalamin) at 100 mcg monthly is the definitive treatment for pernicious anemia after initial loading doses. 1
Initial Treatment Protocol
The FDA-approved loading regimen consists of 100 mcg intramuscular or deep subcutaneous cyanocobalamin daily for 6-7 days, followed by alternate-day dosing for seven doses, then every 3-4 days for 2-3 weeks until hematologic values normalize. 1 This aggressive initial approach is critical because neurological sequelae may become irreversible if treatment is delayed. 2, 3
Key Points About Route of Administration:
- Avoid intravenous administration—almost all vitamin will be lost in urine 1
- Oral vitamin B12 is not dependable for pernicious anemia because the fundamental defect is malabsorption due to intrinsic factor deficiency or autoantibodies 1, 4
- Intramuscular or deep subcutaneous injection is the standard of care 1, 5
Maintenance Therapy
After the loading phase, administer 100 mcg intramuscular cyanocobalamin monthly for life. 1 This is non-negotiable—pernicious anemia requires lifelong replacement therapy because the autoimmune destruction of parietal cells is permanent. 5, 4
Diagnostic Confirmation in Older Adults
Before initiating treatment, confirm the diagnosis with:
- Serum vitamin B12 level (<150 pg/mL indicates severe deficiency) 6
- Anti-intrinsic factor antibodies (highly specific for pernicious anemia) 6, 4
- Anti-parietal cell antibodies (present but less specific) 6, 3
- Complete blood count showing macrocytic anemia (elevated MCV >100 fL) 6
- Methylmalonic acid and homocysteine levels (more sensitive functional markers if B12 results are equivocal) 7
The presence of anti-intrinsic factor antibodies is diagnostic and eliminates the need for Schilling test in most cases. 4
Clinical Presentation to Recognize
Older adults with pernicious anemia may present with:
- Neurological symptoms (weakness, ataxia, paresthesias, decreased sensation, hyperreflexia) that may precede or occur without hematological abnormalities 3, 7
- Hematological manifestations (fatigue, pallor, macrocytic anemia) 2, 6
- Gastrointestinal symptoms (glossitis, angular stomatitis) from the underlying autoimmune gastritis 8
- Psychiatric symptoms (depression, psychosis, cognitive impairment) 3, 7
Critical pitfall: One-third of pernicious anemia cases present with neurological symptoms in the absence of macrocytic anemia. 7 Do not wait for anemia to develop before treating suspected B12 deficiency in older adults with neurological findings.
Concomitant Deficiencies
If folate deficiency coexists, administer folic acid concomitantly with B12 replacement. 1 Never give folate alone without B12 in suspected pernicious anemia, as this can precipitate or worsen neurological deterioration. 5
Older adults with pernicious anemia frequently have multiple vitamin deficiencies:
- Screen for and treat concurrent iron deficiency, which is common in autoimmune gastritis 7
- Check folate levels, as deficiency occurs in inflammatory bowel conditions 7
Monitoring Response
Expected response to treatment includes:
- Reticulocyte response within 5-7 days 1
- Improvement in neurological symptoms within days to weeks 3
- Normalization of hematologic values within 2-3 weeks 1
If there is no clinical improvement or reticulocyte response, reconsider the diagnosis or look for additional contributing factors (concurrent iron deficiency, folate deficiency, ongoing blood loss, or misdiagnosis). 5
Long-term Considerations
- Pernicious anemia is associated with other autoimmune conditions (thyroid disease, vitiligo, type 1 diabetes), which are common in older adults 3, 4
- Patients require lifelong monitoring for gastric cancer risk due to chronic atrophic gastritis, though this is beyond acute management 4
- Ensure medication adherence to monthly injections, as discontinuation will lead to recurrence of deficiency 5