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Macrocytic anaemia: B12 and folate deficiency
An MCV above 100 divides into megaloblastic anaemia (B12 or folate, with hypersegmented neutrophils) and non-megaloblastic causes (alcohol, liver, hypothyroidism, reticulocytosis, MDS and drugs); in B12 deficiency, folic acid is never given alone.
Why it matters in the exam
The typical question presents an older patient with macrocytic anaemia, numb feet, unsteady gait and cognitive change — B12 deficiency with damage to the posterior and lateral columns of the spinal cord. The candidate must remember the causes: pernicious anaemia (antibodies to intrinsic factor and to gastric cells), long-term metformin and PPIs, a vegan diet, ileal resection or Crohn's disease, and bariatric surgery. When the B12 level is borderline — a high methylmalonic acid and homocysteine confirm B12 deficiency, whereas in folate deficiency only homocysteine is high.
A fixed trap: giving folic acid alone to a patient with B12 deficiency improves the anaemia but worsens the nerve damage — so B12 is checked and corrected first. Treatment: intramuscular B12 (1000 µg) — frequent doses at first and then monthly or by protocol — and in a patient without neurological symptoms high-dose oral B12 (1000–2000 µg a day) also works, even in pernicious anaemia. In the first days of treatment hypokalaemia can occur because of rapid cell production. Folate deficiency (alcohol, malnutrition, pregnancy, methotrexate) is treated with folic acid for about 4 months. Drugs that raise the MCV: methotrexate, hydroxyurea and zidovudine.
Key points
- MCV above 100: megaloblastic (B12, folate) versus non-megaloblastic.
- B12 deficiency: high MMA and homocysteine; in folate deficiency only homocysteine.
- B12 1000 µg intramuscularly, or oral 1000–2000 µg a day.
- Do not give folic acid alone before excluding B12 deficiency.
- Causes: pernicious anaemia, metformin, PPI, vegan diet, ileum.
Summary table
| Type | Clues | Test | Treatment |
|---|---|---|---|
| B12 deficiency | Pernicious anaemia, metformin, PPI, vegan diet, ileum | Low B12; high MMA and homocysteine | B12 1000 µg intramuscularly, or oral 1000–2000 µg a day |
| Folate deficiency | Alcohol, malnutrition, pregnancy, methotrexate | Low folate; only homocysteine high | Folic acid for about 4 months, after excluding B12 deficiency |
| Pernicious anaemia | Autoimmune, atrophic gastritis | Intrinsic factor antibodies | Lifelong B12; risk of gastric cancer and carcinoid |
| Non-megaloblastic | Alcohol, liver disease, hypothyroidism, reticulocytosis | TSH, liver tests, reticulocytes | Treat the cause |
| MDS | Older patient, other cytopenias | Film and bone marrow examination | By risk |
| Drugs | Methotrexate, hydroxyurea, zidovudine | High MCV | Usually no treatment needed |
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Sources
- British Society for Haematology Guidelines for the diagnosis and treatment of cobalamin and folate disorders, 2014 — Diagnosis and replacement
- Harrison's Principles of Internal Medicine, 21st edition (2022) — Megaloblastic Anemias
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-02. The text may contain errors; when in doubt, check the source.