Paroxysmal nocturnal hemoglobinuria and liver transplantation: a new paradigm with proximal complement inhibition

Paroxysmal nocturnal hemoglobinuria (PNH) is caused by an acquired somatic mutation of the phosphatidylinositol glycan class A gene. It is characterized by complement-mediated intravascular hemolysis, an increased risk of thrombosis, and varying degrees of bone marrow failure. Budd-Chiari syndrome is a rare but severe thrombotic complication associated with PNH. We present the case of a 57-year-old man with a history of aplastic anemia who developed classic PNH, complicated by multiple thrombotic events and two liver transplants. Despite treatment with eculizumab, with adequate therapeutic levels and effective blockade of the terminal complement pathway, he presented persistent anemia with transfusion dependence and elevated hemolysis markers such as lactate dehydrogenase (LDH). Given the suspicion of extravascular hemolysis, treatment with pegcetacoplan, a proximal complement inhibitor, was initiated, achieving normalization of LDH and significant improvement in hemoglobin levels, reaching transfusion independence. However, due to the recurrence of severe hemolytic crises, treatment was ultimately switched to iptacopan, resulting in remission of the crises and clinical and laboratory stability of the patient. This case illustrates the usefulness of proximal complement blockade with anti-C3 agents in PNH patients with liver transplantation and suboptimal control under anti-C5 therapy.