Free haemoglobin has a toxic effect on endothelium, which precipitates thrombosis formation. In the case of decreased or absent complement inhibition, the state of complement overactivation is achieved, which leads to intravascular haemolysis that gives rise to a leak of haemoglobin to circulation ( 2). The main purpose of these proteins is to inhibit complement activation on membrane surface. The main mechanism in pathophysiology of PNH is a deficiency of CD55 and or CD59 on the surface of blood cells. PNH is a potentially life threating disease associated with intravascular and frequently also with extravascular haemolysis, thromboembolic events, and in some cases with myelodysplastic syndrome (MDS) or aplastic anaemia AA ( 1). These mutations could lead to the production of deficient blood cells with a decreased or totally absent resistance to complement, which leads to the episodes of haemolysis. These genes are responsible for anchoring of several proteins such as CD55 and CD59 on the surface of blood cells. PNH is caused by a somatic mutation of genes on X chromosome, usually PIGA gene is involved. The 6-year survival of patients treated since 2005 is 92 %, and median survival has increased significantly due to the use of Eculizumab and improvements in both supportive measures and management of disease complications.Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal disease of hematopoetic stem cell, without malignant potential. Bone marrow transplantation can cure PNH but is only indicated in case of severe associated medullar aplasia, due to the severe complications of this technique in this context. It reduces significantly the hemolysis, the need of transfusions, fatigue, the occurrence of thrombosis, the risk of renal failure, and improves the patients' survival. In June 2007, the monoclonal antibody Eculizumab received an orphan drug designation in Europe for the treatment of PNH. Until 2007, treatment was primarily symptomatic: transfusions, use of anticoagulants and treatment of an associated aplasia. Differential diagnosisÄifferential diagnoses include all the other forms of anemia (in particular autoimmune hemolytic anemia) and other causes of deep vein thromboses, according to their clinical presentation. Molecular analysis is unreliable for diagnosis as the causative mutations are non-homogenous and non-repetitive. Diagnosis is confirmed by flow cytometry to detect GPI-linked antigen deficiency in red cells, monocytes and granulocytes. Diagnostic methodsÄiagnosis is based on the clinical features and presence of hemolytic anemia, especially since it is associated with thrombosis and/or peripheral blood cytopenia. The mutation occurs in one or several hematopoietic stem cell(s) and leads to a lack (total or partial) of all GPI-anchored cell membrane proteins (the most important being CD55 and CD59, involved in the regulation of hemolysis due to complement). PNH is caused by somatic mutations in the PIGA gene (Xp22.1), encoding a protein involved in the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor. Bone marrow failure may occur prior, along, or as a late complication of the disease (40-50 % of cases). PNH is a chronic disease with hemolytic crises that may be triggered by several factors such as common infection, vaccination, surgery or certain antibiotics. Depending on their localization, thromboses (which affect 30-40 % of untreated patients) may manifest as abdominal pain, hepatomegaly, ascites and headaches. Hemoglobinuria results in the production of classically dark urine during the night and in the morning (about 25 % of patients), and patients may present with renal insufficiency. Pallor, fatigue and stress dyspnea with activity are the usual manifestations. The variable clinical manifestations include hemolytic anemia, medium and large vessel thrombosis (mainly involving the hepatic, abdominal, cerebral, and dermal veins), and moderate to severe hematopoietic deficiency that may lead to pancytopenia. The disease may occur at any age but it preferentially affects young adults. Higher frequency is suggested in Southeast Asia and in the Far East. An incidence estimate of about 1/770,000/year has been reported with a predicted prevalence of approximately 1/62,500 in Great Britain. Although PNH has been described worldwide, exact prevalence data are not available.
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