Management of Megaloblastic Anaemia
Vitamin B12 deficiency must be identified and treated immediately before initiating folic acid therapy, as folate supplementation can mask severe B12 depletion and precipitate irreversible neurological damage. 1, 2
Immediate Diagnostic Priority
The critical first step is distinguishing between vitamin B12 and folate deficiency, as this determines treatment and prevents catastrophic complications:
- Measure both serum vitamin B12 and folate levels before initiating any treatment 3, 4
- Look for macrocytic anaemia (MCV > 100 fL) with characteristic megaloblastic morphology in bone marrow 3
- Assess for neurological involvement: unexplained sensory/motor symptoms, gait disturbances, memory loss, or peripheral neuropathy 1, 3
- Check reticulocyte count (typically low, indicating decreased RBC production) 3
Common pitfall: Administering folic acid to patients with undiagnosed anaemia can obscure pernicious anaemia diagnosis by correcting haematologic abnormalities while allowing neurologic complications to progress to severe, irreversible nervous system damage 2
Treatment Algorithm
Vitamin B12 Deficiency
With neurological involvement (sensory/motor symptoms, gait abnormalities, cognitive changes):
- Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement 1
- Then hydroxocobalamin 1 mg intramuscularly every 2 months for life 1
- Seek urgent specialist advice from neurology and haematology 1
Without neurological involvement:
- Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 1
- Then maintenance with 1 mg intramuscularly every 2-3 months for life 1
- Alternative: Parenteral B12 1000 μg intramuscularly daily for 1 week, then weekly for 1 month, then monthly for life in pernicious anaemia 3
Evidence note: While one small study suggested oral cobalamin (1000 μg daily) may be as effective as intramuscular treatment 5, current guidelines prioritize parenteral administration, especially for severe deficiency or neurological symptoms 1, 3. Oral therapy should only be considered after excluding malabsorption and in patients without neurological involvement.
Folate Deficiency
Critical safety step: Exclude vitamin B12 deficiency first 1, 2
- Oral folic acid 5 mg daily for minimum of 4 months 1
- Investigate underlying causes: non-adherence to multivitamin supplementation, malabsorption, or medications (anticonvulsants, sulfasalazine, methotrexate) 1
- FDA-approved indication: megaloblastic anaemias due to folate deficiency (tropical/nontropical sprue, nutritional deficiency, pregnancy, infancy, childhood) 2
Warning from FDA labeling: Folic acid in doses above 0.1 mg daily may obscure pernicious anaemia by producing haematologic remission while neurologic manifestations remain progressive 2
When Diagnosis is Uncertain
If serum vitamin levels are unavailable or results are delayed in a patient with severe anaemia:
- Treat with both vitamins simultaneously 6, 4
- This prevents neurological deterioration while awaiting definitive diagnosis 6
- Retrospectively differentiate based on: gastric analysis, small-bowel imaging, Schilling test, and clinical response pattern 6
Monitoring Response
- Assess for reticulocytosis between days 5-10 of treatment (indicates therapeutic response) 5
- Monitor haemoglobin, MCV, white blood cell count, and platelet count at days 10,30, and 90 5
- Neurological improvement should be evident by day 30 in responsive cases 5
- Re-measure serum vitamin B12 concentration at day 90 to confirm adequacy 5
Additional Considerations
- Exclude other causes of macrocytosis: alcoholism, myelodysplastic syndromes, drugs (hydroxyurea, diphenytoin) 3
- Investigate sources of blood loss in iron deficiency anaemia that may coexist 1
- Consider drug interactions: phenytoin's anticonvulsant action is antagonized by folic acid; patients may require increased doses 2
- In pregnancy, folic acid requirements are markedly increased and deficiency causes fetal damage 2