Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired clonal hematologic disorder characterized by intravascular destruction of red blood cells by the complement system. This intravascular hemolysis can lead to a constellation of symptoms, including anemia, fatigue, shortness of breath, smooth muscle dystonia, and dark urine that is classically prominent in the morning. Paroxysmal nocturnal hemoglobinuria can be a deadly disease with significant morbidity and mortality associated with bone marrow failure and thrombosis. Although it has historically been a life-threatening disease from extensive thrombosis, advancements in treatment have significantly improved the prognosis for individuals with PNH. It is a disease that has garnered much interest, given its intersectionality of hemolytic anemia, complement system dysregulation, marrow failure syndromes, thrombophilia, and the emergence of targeted therapies. While complement inhibitors have transformed the treatment landscape for PNH, allogeneic hematopoietic stem cell transplant remains the only curative option. Early diagnosis and treatment are crucial for improving outcomes in individuals with PNH. With ongoing research and the development of novel therapies, the outlook for individuals with PNH continues to improve. Focusing on clinically relevant articles available through MEDLINE, this article provides a contemporary, succinct review of classic PNH with predominant features of intravascular hemolysis, encompassing its pathophysiology, epidemiology, clinical manifestations, diagnosis, treatment, and outcomes.