DR Medhat MRCP

Paroxysmal nocturnal hemoglobinuria (PNH)
- It is an acquired disorder leading to hemolysis (mainly intravascular) of hematological
cells.
- It is thought to be caused by ↑ sensitivity of cell membranes to complement due to
a lack of glycoprotein glycosyl-phosphatidyl-inositol (GPI) due to somatic mutation
سؤال (post translational modification) in the haematopoietic stem cell
- Patients are more prone to venous thrombosis.
- It`s a rare disease with median survival is 10 years.
• Pathophysiology :
GPI acts as an anchor which attaches surface proteins e.g. decay-accelerating factor
(DAF) & protectin (CD59)to the cell membrane, these surface proteins protect the
cell membrane from being dystroyed by complement (C3) so ,lack of GPI in clonal
stem cells→ surface proteins will not be properly attached to cell membrane →
↑ sensitivity of cell membrane to complement.
Poor attachment of DAF to RBCs
membrane
Poor attachment of CD59 to platelet
membrane
Binding to complement
Binding to complement
Hemolysis
Thrombosis
(platelet aggregation)
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