Complement-targeting therapies in hemolytic diseases

Complement inhibition has revolutionized the management of hemolytic diseases by targeting the underlying drivers of red blood cell destruction in disorders such as paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and cold agglutinin disease. Recent advances have expanded the therapeutic landscape beyond terminal C5 inhibition to proximal strategies targeting C3, factor B, and factor D. These newer agents - such as pegcetacoplan, iptacopan, and danicopan - not only control intravascular hemolysis but also address extravascular hemolysis and offer oral or subcutaneous alternatives. In cold agglutinin disease, the efficacy of the classical pathway inhibitor sutimlimab provides compelling evidence for the therapeutic value of targeting early initiating molecules of the complement cascade. For clinicians, these innovations provide personalized treatment choices based on disease phenotype, hemolysis profile, patient preference, and risk stratification. The evolving complement inhibitor arsenal enables optimized, targeted care and pathway-specific interventions in hemolytic conditions.