Novel insight into paroxysmal nocturnal hemoglobinuria

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is caused by the acquired clonal defect of hematopoietic stem cell and belongs to the “orphan diseases”. This defect is associated with a lack or deficiency of the membrane glycosylphosphatidylinositol-anchored proteins on the surface of the progeny, including complement inhibitors CD55 and CD59, the result of mutation of the PIGA gene. Patients experience chronic hemolysis as the consequence of uncontrolled complement activation. Thrombotic complications are the most common reason of morbidity and mortality. Currently in Poland, due to no access to eculizumab (monoclonal antibody inhibiting the complement and registered to the treatment of PNH patients with hemolysis and the high disease activity), the therapy consists of packed red blood cells transfusions, anticoagulant prophylaxis and allogeneic hematopoietic stem cell transplantation when a matched donor is available. We present the pathomechanism of complex abnormalities observed in PNH including thrombotic complications as well as modern diagnostic and therapeutic guidelines.