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Pathology

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PNH is an acquired membrane disorder usually caused by a mutation in an X - linked gene. PNH cell membranes lack two important glycoproteins - decay accelerating factor (DAF) and homologous restriction factor (HRF) - which normally impede complement activation.

As a result, PNH cells are more sensitive to activated complement since their ability to fix C3b is increased, and the terminal lytic sequence of complement is more able to penetrate the cell membrane. Variations in the degree of complement sensitivity result in part, from differences in the proportion of stem cells affected.

PNH cells also show increased susceptibility to lysis by hydrogen peroxide and reduced acetylcholinesterase activity.


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