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Educational draft · awaiting clinical reviewUse Rapid for revision, not patient-care decisions. Check current national and local guidance and the BNF or BNFC before acting.

Paroxysmal nocturnal haemoglobinuria

Haematology and transfusion · UK scope · Sources checked 27 Aug 2026 · Clinical review pending

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Escalate

Suspected splanchnic, cerebral or other acute thrombosis in PNH needs immediate specialist assessment and imaging while bleeding, platelet count and anticoagulation are addressed. Severe haemolysis can cause acute kidney injury, chest or abdominal pain and oesophageal spasm. A patient receiving terminal-complement inhibition who develops fever, headache, neck stiffness, rash or shock requires emergency antibiotics for possible meningococcal disease; vaccination does not eliminate risk.

Synopsis

Identify complement-mediated intravascular haemolysis and unusual thrombosis, quantify the abnormal clone, distinguish marrow failure overlap, and use complement inhibition with infection safeguards.

  • PNH is an acquired clonal haematopoietic stem-cell disorder caused by a somatic PIGA mutation and loss of glycosylphosphatidylinositol-anchored surface proteins.
  • Deficiency of CD55 and CD59 leaves blood cells vulnerable to complement, producing predominantly intravascular haemolysis, thrombosis and variable marrow failure.
  • Haemoglobinuria may be absent or intermittent; unexplained Coombs-negative haemolysis, abdominal pain, dysphagia, cytopenias or thrombosis at an unusual site should prompt testing.
  • Flow cytometry using FLAER and lineage-specific GPI-linked markers on granulocytes and monocytes establishes and measures the clone; red-cell results are altered by haemolysis and transfusion.
  • Thrombosis may involve hepatic, portal, mesenteric or cerebral veins and is a leading source of morbidity, sometimes preceding obvious haemoglobinuria.
  • PNH frequently overlaps aplastic anaemia or myelodysplastic disease, so clone size must be interpreted alongside marrow cellularity, counts and morphology.
  • Terminal C5 inhibition with eculizumab or ravulizumab reduces intravascular haemolysis and thrombosis in eligible symptomatic disease but increases susceptibility to meningococcal infection.
  • Proximal complement inhibitors may control both intravascular and C3-mediated extravascular haemolysis in selected adults through current NICE and specialist eligibility.
  • Vaccination, antimicrobial planning and explicit emergency fever instructions must precede or accompany urgent complement blockade; neither vaccines nor prophylaxis confer complete protection.
  • Allogeneic stem-cell transplantation can eradicate the clone but is generally reserved for severe associated marrow failure because procedure risk exceeds that of controlled isolated PNH.

    • Key red flags

    Meningococcal warning

    Fever, headache, rash, meningism or shock during complement inhibition requires immediate sepsis treatment and specialist notification.

    Investigation priorities

    01
    Full blood count, reticulocytes and filmFirst step

    Measure anaemia, compensation and additional cytopenias.

    Management branches

    Case findingTest the right haemolytic or marrow phenotype

    Unexplained antiglobulin-negative haemolysis, unusual thrombosis or aplastic cytopenia is present.

    1. Confirm haemolysis and review film, transfusion timing, renal function and all cytopenias rather than screening solely because urine once looked dark.
    2. Request high-sensitivity PNH flow cytometry on granulocytes, monocytes and red cells through an accredited laboratory, documenting recent complement therapy.
    3. Refer a confirmed clone to a specialist PNH or marrow-failure service to classify classical, marrow-overlap or subclinical disease and establish follow-up.

    Key medicines

    RavulizumabFor adults weighing at least 40 kg, give an intravenous loading dose of 2,400 mg at 40 to under 60 kg, 2,700 mg at 60 to under 100 kg or 3,000 mg at 100 kg or more. Give the first maintenance dose 2 weeks later, then 3,000 mg, 3,300 mg or 3,600 mg respectively every 8 weeks; use the licensed switch schedule when changing inhibitor.Vaccinate against available meningococcal serogroups at least 2 weeks before starting where treatment can safely wait; if urgent treatment starts sooner, give appropriate antibiotic prophylaxis until 2 weeks after vaccination. Infection can still progress rapidly despite both measures, so provide an emergency plan and review infusion reactions, weight change and pregnancy planning.
    EculizumabFor adult PNH, give 600 mg intravenously once weekly for 4 weeks, 900 mg in week 5, then 900 mg every 14 days. The specialist service uses supplementary dosing after plasma exchange or infusion according to the product information.Apply the same meningococcal vaccination, antibiotic-bridging and emergency-infection safeguards as for ravulizumab. Monitor for breakthrough haemolysis, infusion effects and loss of control around surgery, pregnancy or other major complement activation.
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    Sources and review status5 sources · checked 27 Aug 2026 · clinical review pending+
    Sources

    Sources and review status

    National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.

    • ICCS and ESCCA PNH flow-cytometry consensusHigh-sensitivity clone detection and reporting across granulocytes, monocytes and red cells.
    • NICE ravulizumab technology appraisalNHS use of ravulizumab for eligible adults with PNH.
    • NICE iptacopan technology appraisalCurrent NHS positioning of proximal complement inhibition for selected PNH anaemia.
    • Ravulizumab summary of product characteristicsLicensed weight-based dosing, switching, meningococcal prevention and safety for ravulizumab.
    • Eculizumab summary of product characteristicsLicensed PNH induction, maintenance, supplementary dosing and infection safeguards for eculizumab.

    Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes

    Authoring stateRapid draftClinical stateAwaiting reviewJurisdictionUnited Kingdom