Management issues in paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) arises in the setting of bone marrow injury. Thus, management decisions must take into account whether symptoms are a consequence of the underlying marrow failure or of the expansion of the clone of the PIG-A mutant hematopoietic cells. The primary clinical manifestations of PNH are intravascular hemolysis and thrombophilia. Currently available options for treatment of the hemolysis of PNH are unsatisfactory, but the recent development of specific inhibitors of complement for use in treating human disease should make possible effective management of this pathology. The fundamental basis of the thrombophilia of PNH has not been elucidated. Currently, empiric anticoagulant therapy is the foundation for treating the thromboembolic complications of PNH. The role of warfarin prophylaxis, however, remains an area of active debate. Pregnancy in a patient with PNH presents special concerns about fetal/maternal well-being because of the high potential for thromboembolic complications. Bone marrow transplantation can be considered curative, but the decision to recommend this treatment must take into account factors related both to PNH and to comorbid conditions. Refining the technology for both gene therapy (by transducing stem cells with a functional PIG-A gene) and autotransplantation (by using stem cells selected for the expression of glycosyl phosphatidylinositol-anchored proteins) remain challenges for the future.