Mechanism
- Physiologically, a membrane-bound glycosylphosphatidylinositol (GPI) anchor protects RBCs against complement-mediated hemolysis.
- Acquired mutation on the PIGA gene located on the X chromosome → GPI anchor loses its protective effect → RBC destruction by complement and reticuloendothelial system → intravascular and extravascular hemolysis → release of prothrombotic factors from lysed RBCs → thrombosis
- The GPI anchor proteins involved in PNH are:
- CD55/DAF (Decay-accelerating factor)
- CD59/MIRL (Membrane inhibitor of reactive lysis)
- PNH can also occur in patients with aplastic anemia and MDS.
Clinical presentation
- During night → respiratory acidosis → complement activation
- Red or pink urine (from hemoglobinuria)
- Venous thrombosis
- Budd chiari
- Depletion of nitric oxide → smooth muscle dystonia → dysphagia, abdominal pain and erectile dysfunction
Treatment
- Eculizumab (anti C5), ravulizumab, crovalimab
- Steroids (crisis)
- Anti-platelets/anticoagulants
- Bone marrow transplant may be curative
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