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.
Key red flags
Fever, headache, rash, meningism or shock during complement inhibition requires immediate sepsis treatment and specialist notification.
Investigation priorities
Measure anaemia, compensation and additional cytopenias.
Management branches
Unexplained antiglobulin-negative haemolysis, unusual thrombosis or aplastic cytopenia is present.
- Confirm haemolysis and review film, transfusion timing, renal function and all cytopenias rather than screening solely because urine once looked dark.
- Request high-sensitivity PNH flow cytometry on granulocytes, monocytes and red cells through an accredited laboratory, documenting recent complement therapy.
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.
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.