[Advances in complement inhibition therapy for paroxysmal nocturnal hemoglobinuria].

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder. Historically, most PNH patients mainly received supportive treatment, which led to poor quality of life and high mortality rates. The advent of downstream complement C5 inhibitors has dramatically changed the natural course of PNH. These inhibitors alleviate clinical symptoms, significantly reduce severe complications, and improve survival rates. Despite their ability to control intravascular hemolysis and enhance hemoglobin levels, approximately half of the treated patients still require blood transfusions due to extravascular hemolysis (EVH) mediated by upstream complement component C3. Upstream complement inhibitors not only control IVH but also reduce the deposition of C3 fragments, thereby solving the problem of EVH and further improving the clinical outcomes of PNH patients. However, due to the cascade of complement activation and the increased accumulation of PNH red blood cells after treatment with upstream complement inhibitors, there may be an increased risk of more severe breakthrough hemolysis events. Additionally, the potential risk of infections associated with complement inhibitors is another issue that needs to be addressed.