Eculizumab in paroxysmal nocturnal hemoglobinuria with Budd-Chiari syndrome progressing despite anticoagulation

Paroxysmal nocturnal hemoglobinuria (PNH) is a life-threatening, progressive, acquired genetic disease characterized by the clonal, nonmalignant expansion of hematopoietic stem cells deficient in glycosylphosphatidylinositol (GPI) synthesis. This deficiency results in fewer GPI-anchored complement inhibitors (CD55 and CD59) on the cell surface, causing increased chronic complement-mediated intravascular hemolysis and platelet hyperactivation and aggregation [1]. Both processes lead to an increased risk of thrombosis, renal dysfunction and damage, pulmonary hypertension, and anemia, which, despite historical treatment regimens, have resulted in up to 35% mortality within 5？years of diagnosis [2]. Thromboembolism is the most common cause of PNH-related death, accounting for two-thirds of all mortalities in patients with this disease [3]. Between 29% and 44% of PNH patients experience a clinically evident thromboembolism, affecting the liver, brain, gut, and kidney [3,4]. Recent registry analyses support an 8.4- to 15.4-fold increased risk of death in patients with PNH with thromboembolism [4,5].Budd-Chiari syndrome (BCS) is common in PNH patients and anticoagulation therapy is traditionally the first treatment choice for the management of this disorder. However, PNH patients frequently experience new thrombotic episodes despite adequate anticoagulation, which limits the usefulness of subsequent hepatic vein angioplasty and/or stenting and transjugular intrahepatic porto-systemic shunt (TIPS) placement [3,6,7]. Further complicating anticoagulation management, thrombocytopenia occurs in 25% to 52% of PNH patients, creating a high risk of severe bleeding [5,8]. Additional therapeutic options for BCS in patients with PNH are limited to high-risk allogeneic hematopoietic stem-cell transplantation or liver transplantation. In one retrospective study in patients with PNH, there was a 22% reduction in 5-year survival in patients who had received stem-cell transplantation comp