![]() Third, although it is due to an intrinsic abnormality of the red cell, it is an acquired disorderĢ. Second, it is a thrombophilic condition in which it is not unusual for thrombosis to take place, paradoxically, in a thrombocytopenic patient. First, it is a hemolytic anemia, but, unlike any other hemolytic anemia, it is frequently associated with pancytopenia. Paroxysmal nocturnal hemoglobinuria (PNH) is a unique disorder in more ways than oneġ. Indeed, GPI-specific CD8+ T cells – which have been identified in PNH patients – would spare selectively GPI-negative stem cells, thus enabling them to re-populate the marrow of a patient who would otherwise have aplastic anemia. This brief review focuses on two specific aspects of PNH: (1) response to eculizumab, variability of response, and how this new agent has impacted favorably on the outlook and on the quality of life of patients and (2) with respect to pathogenesis, new evidence supports the notion that expansion of the PNH clone results from T-cell-mediated auto-immune damage to hematopoietic stem cells, with the GPI molecule as target. Since 2007, PNH has received renewed and much wider attention because a new form of treatment has become available, namely complement blockade through the anti-C5 monoclonal antibody eculizumab. Until a decade ago, the treatment options for PNH were either supportive treatment – often including blood transfusion, anti-thrombosis prophylaxis, and sometimes thrombolytic therapy – or allogeneic bone marrow transplantation. PIG-A, are deficient in glycosylphosphatidylinositol (GPI)-linked proteins: since these include the surface membrane complement-regulatory proteins CD55 and CD59, the red cells arising from this clone are exquisitely sensitive to lysis by activated complement. PNH results from expansion of a clone of hematopoietic cells that, as a consequence of an inactivating mutation of the X-linked gene ![]() Paroxysmal nocturnal hemoglobinuria (PNH) is a very rare disease that has been investigated for over one century and has revealed unique aspects of the pathogenesis and pathophysiology of a hemolytic anemia.
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