This study evaluates the effectiveness and safety of intensive subcutaneous (SC) or intravenous (IV) pegcetacoplan treatment in managing acute breakthrough hemolysis (BTH) events in patients with paroxysmal nocturnal hemoglobinuria (PNH) on pegcetacoplan therapy. Pegcetacoplan, a proximal complement C3 inhibitor, is designed to control both intravascular and extravascular hemolysis in PNH patients. The study included 13 patients who experienced acute BTH, with 9 receiving SC dosing and 4 receiving IV dosing. Intensive treatment was found to be safe and well-tolerated, with a rapid reduction in lactate dehydrogenase (LDH) levels and stabilization of hemoglobin levels in most patients. All adverse events associated with the acute BTH event were resolved, and no thromboembolic events were reported. The study supports the use of intensive pegcetacoplan dosing as an effective management strategy for acute BTH events in PNH patients.This study evaluates the effectiveness and safety of intensive subcutaneous (SC) or intravenous (IV) pegcetacoplan treatment in managing acute breakthrough hemolysis (BTH) events in patients with paroxysmal nocturnal hemoglobinuria (PNH) on pegcetacoplan therapy. Pegcetacoplan, a proximal complement C3 inhibitor, is designed to control both intravascular and extravascular hemolysis in PNH patients. The study included 13 patients who experienced acute BTH, with 9 receiving SC dosing and 4 receiving IV dosing. Intensive treatment was found to be safe and well-tolerated, with a rapid reduction in lactate dehydrogenase (LDH) levels and stabilization of hemoglobin levels in most patients. All adverse events associated with the acute BTH event were resolved, and no thromboembolic events were reported. The study supports the use of intensive pegcetacoplan dosing as an effective management strategy for acute BTH events in PNH patients.