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Paroxysmal nocturnal hemoglobinuria: a complement-mediated hemolytic anemia.

Paroxysmal nocturnal hemoglobinuria is manifests with a chronic hemolytic anemia from uncontrolled complement activation, a propensity for thrombosis and marrow failure. The hemolysis is largely mediated by the alternative pathway of complement. Clinical manifestations result from the lack of specific cell surface proteins, CD55 and CD59, on PNH cells. Complement inhibition by eculizumab leads to dramatic clinical improvement. While this therapeutic approach is effective, there is residual complement activity resulting from specific clinical scenarios as well as from upstream complement components that can account for suboptimal responses in some patients. Complement inhibition strategies are an area of active research.

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