Mechanisms of hemolysis in paroxysmal nocturnal hemoglobinuria

Mechanisms of red blood cell hemolysis in PNH.
(A) Normal red blood cells have GPI-linked complement inhibitors CD59 and CD55, which prevent intravascular and extravascular hemolysis, respectively.
(B) In PNH, CD59 and CD55 are deficient due to lack of the GPI anchor. Intravascular hemolysis caused by the complement membrane attack complex (MAC) predominates.
(C) Eculizumab is a humanized monoclonal antibody to complement component C5 that blocks C5 conversion to C5a and C5b and prevents intravascular hemolysis. Eculizumab does not block extravascular hemolysis due to lack of CD55.
Refer to UpToDate topics on PNH pathogenesis and treatment for further details.