AKT · Haematology/Anaemia & red cell

B12 & folate deficiency

Deficiency of B12 (pernicious anaemia/malabsorption/diet) or folate → megaloblastic macrocytic anaemia

Overview

Deficiency of vitamin B12 or folate impairs DNA synthesis, producing a megaloblastic macrocytic anaemia (hypersegmented neutrophils, oval macrocytes). B12 deficiency is most often pernicious anaemia (autoimmune loss of intrinsic factor) and uniquely causes neurological disease — subacute combined degeneration of the cord. The cardinal rule: replace B12 BEFORE folate, because giving folate alone in B12 deficiency can precipitate/worsen the neuropathy.

Recognise

Macrocytic anaemia (MCV >100); blood film — oval macrocytes, HYPERSEGMENTED neutrophils; glossitis, mild jaundice
B12 deficiency neurology: subacute combined degeneration (dorsal columns + corticospinal) — paraesthesiae, reduced proprioception/vibration, ataxia; peripheral neuropathy; cognitive change
Causes — B12: pernicious anaemia (anti-IF/parietal-cell antibodies), gastrectomy, terminal ileal disease (Crohn), vegan diet, metformin; folate: poor diet, pregnancy, malabsorption, methotrexate/anticonvulsants, haemolysis

Red flags

B12-deficiency neurology (subacute combined degeneration) → urgent B12 replacement; do NOT give folate first
Pernicious anaemia → lifelong B12; raised gastric-cancer risk

Differentials & how to tell them apart

Non-megaloblastic macrocytosisalcohol, liver disease, hypothyroidism, myelodysplasia — no hypersegmented neutrophils, normal B12/folate

Haemolysis (reticulocytosis)raised reticulocytes can raise the MCV — high LDH/bilirubin, low haptoglobin

Myelodysplasiamacrocytosis with cytopenias/dysplasia — marrow examination

Hypersegmented neutrophil of megaloblastic anaemia (blood film)
Ed Uthman / CC BY 2.0 — Wikimedia Commons

Investigations

FBC (macrocytic), blood film (oval macrocytes, hypersegmented neutrophils), B12 and folate levels; intrinsic-factor/parietal-cell antibodies (pernicious anaemia); reticulocytes; exclude other macrocytosis causes (TFTs, LFTs, alcohol, myelodysplasia).

Management

Replace B12 (IM hydroxocobalamin) BEFORE folate; treat the cause

1Confirm a megaloblastic macrocytic anaemia (oval macrocytes, hypersegmented neutrophils) and measure B12 and folate; test for pernicious anaemia (anti-intrinsic-factor antibodies).Gate: Replace B12 BEFORE folate — giving folate alone when B12 is deficient can precipitate or worsen subacute combined degeneration of the cord. B12-deficiency neurology needs prompt B12.
2Lifelong IM B12 for pernicious anaemia; oral folate for folate deficiency (and in pregnancy); treat dietary/malabsorptive/drug causes; monitor the reticulocyte response.

Replace B12 FIRST (IM hydroxocobalamin), then folate — the cardinal rule — folate alone in B12 deficiency can precipitate/worsen subacute combined degeneration; pernicious anaemia needs lifelong B12

Folic acid (oral) — for folate deficiency (and prophylactically in pregnancy); only after B12 is confirmed replete

Treat the cause — pernicious anaemia (lifelong B12), dietary advice, manage malabsorption/culprit drugs (metformin, methotrexate)

Monitor response — reticulocytosis within days; recheck FBC

Key points

Macrocytic anaemia + oval macrocytes + HYPERSEGMENTED neutrophils = megaloblastic (B12/folate). B12 deficiency uniquely causes subacute combined degeneration (dorsal columns + corticospinal) — and you must give B12 BEFORE folate or you can precipitate it. Pernicious anaemia (anti-IF) = lifelong B12.

Monitor & prognosis

Reticulocyte/FBC response, neurological recovery, B12/folate levels; pernicious anaemia surveillance.

Haematological recovery is prompt; established neurological damage may be irreversible if treatment is delayed.

Source: BSH cobalamin/folate; cross-ref neurology (SACD)