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Arch Hellen Med, 26(4), July-August 2009, 454-478


Paroxysmal nocturnal hemoglobinuria: Clinical presentation, diagnosis and treatment

1First Department of Internal Medicine, National and Kapodistrian University of Athens, School of Medicine, "Laiko" General Hospital,
2Department of Medical Research, 251 General Air Force Hospital, Athens, Greece

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder of hematopoietic stem cell characterized by the presence of intravascular hemolysis, marrow failure, nocturnal hemoglobinuria, thrombosis and rarely leukemia transformation. PNH is related to a somatic mutation in the phosphatidylinositol glycan class A (PIG-A), X-linked gene, responsible for a deficiency in glycosylphosphatidylinositol-anchored proteins (GPI-APs). The lack of GPI-APs complement regulatory proteins CD55 and CD59 leads to hemolysis. The diagnosis is based on flow cytometry, which allowed direct quantification of the GPI-AP-deficient cells. The clinical polymorphism of PNH has been recognized by four presentations; one form, predominantly hemolytic without overt marrow failure, referred to classic PNH, one with marrow failure that is often described as the aplastic anemia PNH syndrome (AA-PNH), a very mild disease with almost no symptoms (mini-PNH), and the hypoplastic form of PNH. Thromboses remain a major life threatening complication affecting outcomes in all disease subcategories. Thrombotic events are characterized by involvement of unusual sites (hepatic, mesenteric, cerebral, dermal veins). Treatment of PNH is mainly symptomatic. Allogeneic bone marrow transplantation is the only curative option in case of severe complications during the course of the diseases. A new targeted treatment strategy is the inhibition of the terminal complement cascade with the monoclonal antibody eculizumab which is a C5-inhibitor humanized monoclonal antibody. In classic PNH recent studies have shown that eculizumab is efficient to reduce complement mediated intravascular hemolysis, reduce the need for transfusions, improve the quality of life in patients with PNH and reduce the risk for thromboembolic complications, which are the main cause of mortality in PNH. Concerning the AA-PNH syndrome, allogeneic bone marrow transplantation is the reference treatment in young patients with a sibling donor. Immunosuppressive therapy remains an important treatment modality in this subcategory for patients without a donor or ineligible for BMT. Recurrent thrombotic events remains even now associated with bad prognosis, whatever the form of the disease.

Key words: CD55, CD59, Clinical presentation, DAF, MIRL, Paroxysmal nocturnal hemoglobinuria, Treatment.

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