Consensus on Complement Inhibitor Therapy and Management of Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH), a rare clonal disease of hematopoietic stem cells caused by mutations in the phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) gene, may lead to the deficiency of glycosylated phosphatidylinositol (GPI)-anchored proteins. This deficiency further results in the red blood cells of PNH patients becoming more susceptible to complement-mediated attack, thus triggering a range of hemolysis-related symptoms including intravascular hemolysis (IVH), thrombosis, and smooth muscle dysfunction, which severely compromises patients′ quality of life and may even lead to death. Traditional therapeutic approaches have been ineffective in addressing the cascade reactions initiated by abnormal activation of the complement system; therefore, hematopoietic stem cell transplantation (HSCT) was once regarded as the sole cure for PNH. However, with the advent of complement inhibitors targeting complement components, which can block the complement cascade pathway and effectively control hemolysis and related symptoms, these drugs have emerged as the first-line therapy for hemolytic PNH. In recent years, multiple complement inhibitors have been approved globally and launched in China, enabling a growing number of Chinese patients to receive treatment with these agents. This consensus aims to standardize and guide the clinical application of various complement inhibitors in the field of PNH.