Danicopan add-on therapy for extravascular hemolysis in a patient with paroxysmal nocturnal hemoglobinuria receiving ravulizumab

INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated hemolysis. Although C5 inhibitors effectively control intravascular hemolysis, some patients develop clinically significant extravascular hemolysis (EVH) because of upstream C3 deposition. CASE: A 56-year-old woman was diagnosed with PNH in 2019 and managed with intermittent transfusions. In October 2024, she developed progressive renal dysfunction; the PNH clone size was 95.72%. Ravulizumab was initiated in March 2025. Although the lactate dehydrogenase (LDH) level normalized after ravulizumab initiation, her hemoglobin (Hb) level remained below 10 g/dL, with marked reticulocytosis and continued transfusion requirements after more than 6 months of treatment. Danicopan, a factor D inhibitor, was added in November 2025. Subsequently, her Hb level exceeded 10 g/dL, reticulocyte counts gradually decreased, and transfusion dependence declined. DISCUSSION: This case demonstrates that adding danicopan to ravulizumab can reduce residual EVH and improve anemia in patients with PNH receiving C5 inhibitor therapy.