Reasoning GP · Algorithm · 1-page summary
Macrocytosis (raised MCV) in adults
For: adults with an MCV >100 fL on FBC, in hours or OOH. Not for: children. Known B12 deficiency or low folate → their own algorithms.
Core rule: read the whole FBC and the film, not the MCV alone. Cytopenias, blasts or dysplasia → haematology; neurological symptoms → IM B12 now, without waiting for results; always replace B12 before folate.
0Stop — call 999 now
- Severe symptomatic anaemia (often megaloblastic ± pancytopenia) with chest pain, syncope, hypoxia, heart failure, confusion or haemodynamic compromise → 999
- Macrocytosis with liver disease and variceal bleeding or haemodynamic compromise → 999
- While waiting: bloods only if they do not delay treatment. Transfusion is a clinical decision — never withheld because the cause is B12 or folate.
1Triage — the whole picture, not the MCV
| Finding | Action |
|---|---|
| Blasts or cytopenias | Blasts, suspected leukaemia, unexplained pancytopenia, rapidly falling counts, neutropenia with fever, bleeding → Same-day haematology/acute discussion |
| Neuro + low B12 | IM hydroxocobalamin now; severe or rapidly progressive → Same-day medical/neurological |
| MCV >110–120 fL | Progressive, or with anaemia, cytopenias, abnormal film or neuro symptoms → Urgent clinical review ± haematology |
| Isolated, stable | Normal Hb and counts → block 3 work-up; not automatically urgent |
2Screen — serious causes
- Rapidly progressive weakness, sensory loss, unsteady gait + low/borderline B12 (SACD) → IM B12 urgently; Same-day assessment if severe or rapidly progressive; Urgent if uncertain.
- On methotrexate + oral ulcers + marrow suppression → withhold; urgent FBC, renal and liver tests; assess for sepsis; contact specialist/acute team → Same-day
- Jaundice, hepatomegaly, raised ALT + heavy alcohol → urgent LFTs + coagulation; decompensated (ascites, encephalopathy) → Same-day hospital
- Unexplained cytopenia or dysplastic film, especially over 60 (?MDS) → Urgent haematology.
- Trimethoprim or co-trimoxazole with methotrexate → avoid: potentially life-threatening marrow toxicity.
3Assess — first line for all
☐ Repeat FBC if unexpected; review trends ☐ Blood film ☐ B12 or active B12, folate ☐ TSH ☐ LFTs + GGT, renal function ☐ Reticulocytes ☐ Drug, alcohol (AUDIT-C), diet and nitrous oxide history
Haemolysis? bilirubin, LDH, haptoglobin, DAT. Second line: anti-intrinsic factor antibodies, tTG IgA + total IgA.
4Classify — the film splits the causes
- Megaloblastic — macro-ovalocytes, hypersegmented neutrophils → B12/folate deficiency (pernicious anaemia, diet, metformin, malabsorption, nitrous oxide).
- Alcohol / liver — round macrocytes, target cells, raised GGT → address alcohol; check B12 and folate.
- Hypothyroid — raised TSH → levothyroxine; check B12 too.
- Drugs — methotrexate, hydroxycarbamide, azathioprine, antiretrovirals → review with the prescriber/specialist.
- Reticulocytosis (polychromasia) → haemolysis or bleeding. Clumping, raised MCHC → cold agglutinins: warm repeat FBC, haematology.
- Uncertain — unexplained after first- and second-line tests → haematology (?MDS).
5Treat today — doses: NICE/SPC, BNF, local formulary
- B12 (pernicious anaemia, malabsorption): IM hydroxocobalamin 1 mg ×6 over 2 weeks, then every 2–3 months for life; neurological: alternate days until no further improvement, then 2-monthly. Diet only: oral cyanocobalamin 50–150 micrograms daily.
- Folate deficiency: folic acid 5 mg daily for 4 months, only once B12 is adequate or treated.
- Alcohol: brief intervention; folic acid only if deficiency or a clear ongoing risk. Methotrexate: confirm folic acid 5 mg weekly, on a different day.
- Planning pregnancy: folic acid 400 micrograms daily; 5 mg for higher-risk groups, not for BMI alone (NG247).
6Refer routinely — and follow up
- Haematology: unexplained macrocytosis with anaemia or cytopenia, progressive MCV rise, or persisting after B12/folate correction and alcohol abstinence.
- Gastroenterology: pernicious anaemia with new or worsening upper-GI symptoms → gastroscopy (NG12), not routinely; coeliac disease.
- Follow-up: FBC 4–8 weeks after treating the cause; B12 review at ~3 months; no FBC response at 6 weeks → review diagnosis.
7Never reassure by
- A normal Hb or MCV — neurological B12 deficiency can occur without either.
- A normal B12 level after nitrous oxide use.
- "It's the alcohol" — persisting despite abstinence: look again.
- The MCV alone — no threshold diagnoses MDS; the film and counts matter more.
- Folic acid correcting the MCV while B12 deficiency is untreated (cord damage).
- Repeat vitamin levels instead of investigating persistent macrocytosis.
8Safety-net — say it, then document it
999 “Call 999 if you get chest pain, severe breathlessness, or you faint or collapse.” Same day “Contact us or NHS 111 today if you get a fever, sore throat, mouth ulcers, unusual bruising or bleeding (especially if you take methotrexate), or new numbness, weakness, unsteady walking, or bladder or bowel problems.”
Remote or OOH: any of these → same-day face-to-face assessment; do not wait for the routine blood test or appointment.
✓Safe to leave primary care only if — all five, documented
No block 0–2 row applies
Full FBC and film reviewed: no blasts or unexplained cytopenias
First-line tests, drugs, alcohol and neuro symptoms checked
Cause treated (B12 before folate); FBC recheck date and owner set
Safety-net given and documented
Summary of the full Reasoning GP macrocytosis algorithm, which holds the detail, film findings, drug interactions and evidence. Sources: NICE NG239, NG247, NG12 (updated April 2026); BSH MDS 2021; BCSH cobalamin and folate 2014; BSR csDMARD 2025; SPS methotrexate monitoring. Clinical reference — follow local haematology pathways and check doses: NICE/SPC, BNF.