European journal of haematology
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Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening and debilitating clonal blood disorder caused by an acquired mutation in the phosphatidylinositol glycan (PIG)-A gene. In pluripotent hematopoietic stem cells, this leads to a deficiency of glycosylphosphatidylinositol (GPI)-anchors and GPI-anchored proteins, including the complement regulators CD55 and CD59, on the surface of affected blood cells. PNH red blood cells are highly vulnerable to activation of complement and the formation of the membrane attack complex (MAC). ⋯ A new targeted and disease-modifying treatment strategy is the inhibition of the terminal complement cascade with the humanized monoclonal anti-C5 antibody, eculizumab. This effectively inhibits MAC formation and intravascular hemolysis. Eculizumab has shown significant efficacy in controlled studies, with a marked decrease in anemia, fatigue, transfusion requirements, renal impairment, pulmonary hypertension, and risk of severe thromboembolic events, ultimately resulting in improving quality of life and survival.