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1,9–11 Intravascular hemolysis leads to release of free hemoglobin (Hb) into the blood. These patients manifest with chronic intravascular hemolysis, paroxysmal flares of hemolysis and a propensity for thrombosis. Lack of the complement inhibitor CD59 on the RBCs surface is mostly responsible for the clinical manifestations in PNH. The mechanism of the PIGA mutation is unknown, but the close association between PNH and acquired aplastic anemia (AA) suggests that the immune attack on hematopoietic stem cells provides a conditional survival advantage to the PNH clone. The acquired mutation in PNH occurs in the phosphatidylinositol glycan class A (PIGA) gene, which is responsible for the first step in the synthesis of the glycosylphosphatidylinositol (GPI) anchor, a glycolipid that links dozens of cell-surface proteins to the plasma membrane on hematopoietic cells, including blood group antigens, adhesion molecules and complement regulatory proteins. 8 PNH is chronic, progressive and life-threatening, diagnosed at any age (median age in the early to mid-thirties), affecting males and females equally and despite the best supportive care, it can have a significant impact on mortality, i.e., 5-year and 10-year mortality of 35% and approximately 50%, respectively 1,7 PathophysiologyĪ multistep process seems necessary for PNH to develop. The incidence rate in Great Britain/France is approximately 1.3 cases per million people 7 and 0.13/100,000/year in Yorkshire (United Kingdom). PNH is an acquired clonal disorder of hematopoietic stem cells and its incidence is approximately 1–2 per million, with a prevalence ranging from 10 to 20 per million. In this consensus, we want to emphasize the diagnosis and treatment of the PNH patients, as well as the early recognition of its systemic complications. 3–6 In the last decade, PNH has received novel and much more in-depth attention and a new kind of therapy has become available, the complement blockade by the anti-C5 monoclonal antibody eculizumab. The CD59, whose action is to inhibit the terminal complement cascade leading to the destruction of red blood cells may be more important. Two complement regulatory proteins, the CD55 (decay accelerating factor ) and CD59 (homologous restriction factor or membrane inhibitor of reactive lysis ), were found to be missing from PNH blood cells, explaining the unusual sensitivity of RBCs to the hemolytic action of complement. Granulocytes and platelets are sensitive to the complement, as well. Compared with normal RBCs, PNH RBCs lyse more readily in the presence of the activated complement. 1,2 Hemolysis in PNH is due to the action of the complement on abnormal red blood cells (RBCs). Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, multi-systemic, progressive and life-threatening disease characterized by intravascular hemolysis, thrombotic events, serious infections and bone marrow failure. These procedures express the opinions of experts and have been based on the best available evidence and international guidelines, with the purpose of increasing benefits and reducing harm to patients. ![]() ![]() In this consensus, we are aiming to review the diagnosis and treatment of the paroxysmal nocturnal hemoglobinuria patients, as well as the early recognition of its systemic complications. The treatment that has recently become available is the complement blockade by the anti-C5 monoclonal antibody eculizumab. The traditional therapy for paroxysmal nocturnal hemoglobinuria includes blood transfusion, anti-thrombosis prophylaxis or allogeneic bone marrow transplantation. Early diagnosis, using flow cytometry performed on peripheral blood, the gold standard test to confirm the diagnosis of paroxysmal nocturnal hemoglobinuria, is essential for improved patient management and prognosis. Paroxysmal nocturnal hemoglobinuria results from the expansion of a clone of hematopoietic cells that due to an inactivating mutation of the X-linked gene PIG-A are deficient in glycosylphosphatidylinositol-linked proteins. ![]() Paroxysmal nocturnal hemoglobinuria is a chronic, multi-systemic, progressive and life-threatening disease characterized by intravascular hemolysis, thrombotic events, serious infections and bone marrow failure.
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