Paroxysmal nocturnal haemoglobinuria
- Lesion
An acquired stem cell mutation removes the shields that protect blood cells from complement. Red cells burst, and clots form in unusual veins.
What it is
Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder caused by somatic mutations in PIGA, an X-linked gene needed to make glycosylphosphatidylinositol (GPI) anchors. A single mutation is enough, because only one active X copy exists in each cell. All the progeny of the mutated stem cell lack GPI-anchored proteins, including the complement regulators CD55 (DAF) and CD59 (MIRL). Red cells are lysed by spontaneously activated complement, causing intravascular haemolysis, and patients suffer venous thrombosis, the leading cause of death.
Step by step
- A somatic PIGA mutation arises in a stem cell; the clone cannot build GPI anchors.
- Its red cells, leukocytes and platelets lack CD55 and CD59 on their surface.
- The alternative complement pathway, always idling, forms membrane attack complexes on unprotected red cells.
- Red cells lyse inside vessels: haemoglobinaemia, haemoglobinuria, iron loss in urine.
- Free haemoglobin consumes nitric oxide and complement activates platelets and endothelium: thrombosis.
- The clone expands when autoimmunity damages normal stem cells, as in aplastic anaemia.
Markers
- CD55
- CD59
- FLAER
- PIGA
Clinical notes
- Fatigue, dark urine, abdominal pain, dysphagia and erectile dysfunction from nitric oxide depletion, unexplained abdominal vein thrombosis.
- Complement C5 inhibitors reduce haemolysis and lower the thrombosis risk greatly; stem cell transplantation is the only cure.
- Chronic urinary iron loss can cause iron deficiency.
In the lab
- Flow cytometry for CD55, CD59 and FLAER replaced the old acidified-serum and sucrose lysis tests.
- Direct Coombs negative; high LDH; haemosiderinuria.
Test yourself
Think of the answer, then tap the question to see it.
Why is one PIGA mutation enough to cause PNH, even in women?
PIGA is on the X chromosome, and only one copy is active in each cell because of X inactivation.
Which GPI-linked protein is the most important protector against complement lysis?
CD59 (membrane inhibitor of reactive lysis).
What is the leading cause of death in PNH?
Thrombosis, especially of hepatic, portal, mesenteric and cerebral veins.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Paroxysmal nocturnal hemoglobinuria: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.