Pathogenesis and management of paroxysmal nocturnal haemoglobinuria

Over the past 30 years, our understanding of the pathogenesis of paroxysmal nocturnal haemoglobinuria (PNH) has increased dramatically. During that time, the events during complement activation and regulation have been described, the molecular basis for the exaggerated complement sensitivity of PNH cells has been uncovered, and the responsible gene mutation has been identified. It is now possible to relate almost all the protean manifestations of PNH to a single gene mutation in a haematopoietic stem cell. Unfortunately, our ability to manage these patients has not kept pace, and, with the exception of bone marrow transplantation, our major efforts are still directed toward control of complications rather than interruption of the disease process.