![]() ![]() Advances in the diagnosis and therapy of paroxysmal nocturnal hemoglobinuria. Importância e vantagem da citometria de fluxo frente aos testes de triagem no diagnóstico da hemoglobinúria paroxística noturna. The diagnosis of PNH is made by means of clinical findings and laboratory tests to confirm the degree of hemolysis (haptoglobin, lactate dehydrogenase, direct Coombs test, reticulocyte count and total bilirubin and bilirubin fraction) and deficiency of anchored proteins of the complement system (CD55, CD59 and FLAER) in granulocytes (CD15, CD33 and CD24) and monocytes (CD14 and CD64) by flow cytometry, the gold standard method ( 6 6 Modesto TM, Neves MAB, Brito AE, et al. ![]() Frequency of paroxysmal nocturnal hemoglobinuria in patients attended in Belém, Pará, Brazil. , 5 5 Brito Junior LC, Cardoso MS, Rocha EG, et al. Hemoglobinúria paroxística noturna e gravidez. , 4 4 Nomura ML, Surita FGC, Parpinelli MA, et al. Hemoglobinúria paroxística noturna: da fisiopatologia ao tratamento. Association of PNH clones was observed with other pathologies, such as Coombs-negative hemolytic anemia, bone marrow aplasia, myelodysplastic syndromes, and unexplained thrombosis ( 1 1 Arruda MMAS, Rodrigues CA, Yamamoto M, et al. Spontaneous remission occurs in 10%-15% of PNH cases and the evolution of PNH into acute myeloid leukemia can occur in 5% of the patients. A survival time of 10-15 years is estimated for PNH patients, when not adequately treated thrombosis and progression of pancytopenia are the leading causes of death in 50%-60% of the cases. ![]() In children and teenagers, PNH is observed in just 10% of the diagnosed cases, clinically associated with bicytopenia or pancytopenia, while thrombosis can occur with the same frequency in all age groups. 6 6 Modesto TM, Neves MAB, Brito AE, et al. PNH can occur in any phase of life, just because it is an acquired disease, but it generally affects more young adults aged 35 years on average, and it is more commonly diagnosed between the third and the fifth decades of life ( 4 4 Nomura ML, Surita FGC, Parpinelli MA, et al. ![]() As regards sex, in Europe, PNH is more common in women, whereas in Asia it is more common in men. The same occurs in some Asian countries, such as Thailand, Japan, and the Far East, where PNH has lower incidence than bone marrow aplasia. Still about statistics in the USA, prevalence does not vary by sex or race/ethnicity. The world incidence of PNH is still unknown, but it is estimated to be 1-5 cases per million inhabitants in the USA, a much lower incidence than that of bone marrow aplasia, whose prevalence is 5-10 times higher. Paroxysmal nocturnal hemoglobinuria: stem cells and clonality. Therefore, deficiency of proteins CD55 and CD59 and of the GPI anchor in PNH cells make them sensitive to lysis upon complement, causing chronic intravascular hemolysis, thus cells deficient in PNH will have some different degrees of deficiency for these proteins, either partial (PNH type II cells, with around 10% of normal expression) or total (PNH type III cells, with complete absence of the protein) ( 1 1 Arruda MMAS, Rodrigues CA, Yamamoto M, et al. These markers, yet, lost ground to another marker, the fluorescein-labeled proaerolysin (FLAER), much more specific and precise for the diagnosis of PNH because it binds directly to the GPI anchor. It is essential for the formation of glycosylphosphatidylinositol (GPI) anchor, responsible for anchorage and fixation of certain proteins that regulate the complement system in the outer cell membrane surface of erythrocytes, leukocytes and platelets, such as complement decay-accelerating factor (DAF/CD55) and membrane inhibitor of reactive lysis (MIRL/CD59), formerly used to establish the diagnosis of PNH. The PIG-A gene is located on the short arm of the X chromosome (Xp 22.1), it extends over 17 Kb and contains 6 exons. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal disease of bone marrow stem-cells, genetically characterized by the somatic mutation in the phosphatidylinositol glycan protein A ( PIG-A) gene. ![]()
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