Diagnosis of Paroxysmal Nocturnal Hemoglobinuria: Recent Advances

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder with its protean clinical manifestations. This is due to partial or complete absence of 'glycophosphatidyl-inositol-anchor proteins' (GPI-AP). The main aim of this review is to highlight various diagnostic modalities available, basic principle of each test and recent advances in the diagnosis of PNH. Recently among various tests available, the flow cytometry has become 'the gold standard' for PNH testing. In order to overcome the difficulties encountered by the testing and research laboratories throughout the world, International Clinical Cytometry Society has come up with guidelines regarding the indications for testing, protocol for sample collection, processing, panel of antibodies as well as gating strategies to be used, how to interpret the test and reporting format to be used. It is essential to test at least two GPI-linked markers on at least two different lineages particularly on red cells and granulocytes/monocytes. The fluorescent aerolysin combined with other monoclonal antibodies in multicolour flow cytometry offered an improved assay not only for diagnosis but also for monitoring of PNH clones. It is equally important to diagnose this rare entity with high index of suspicion.

Advances in the creation of animal models of paroxysmal nocturnal hemoglobinuria

“…This is the most direct and simplest method for the diagnosis of PNH. The sequence of hematopoietic cells involved in human PNH cloning is granulocyte → monocyte → erythrocyte → lymphocyte, and to establish the diagnosis of PNH, at least two GPI anchor proteins of one or more types of hematopoietic cells should be missing [32,33]. In a mouse model, the number of GPI-AP-deficient blood cells can be identified by detecting the thermostable antigen (CD24/HSAg) on the surface of mature red blood cells and granulocytes, and CD48 on the surface of lymphocytes.…”

Laboratory involvement in the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria: a case report

“…Existe una asociación bien establecida entre HPN e insuficiencia medular: un 30-45% de pacientes con HPN presentan cierto grado de insuficiencia medular, y un 40-70% de pacientes con aplasia medular alberga un clon HPN detectable. Estos últimos pacientes van a responder mejor a la terapia inmunosupresora, pero tienen riesgo de sufrir una expansión clonal durante la recuperación de la aplasia y desarrollar una HPN manifiesta (6).…”

Paroxysmal Nocturnal Hemoglobinuria Refractory Anemia

“…Paroksismal noktürnal hemoglobinüri (PNH) kazanılmış klonal kök hücre hastalıklarından biridir (3). Hematopoietik kök hücre somatik bir mutasyon sonucu oluşur ve hematopoietik sistemik her 3 serisi birden etkilenir.…”

“…PNH defekti, pig-A geni olarak adlandırılan ve X kromozomunun kısa kolunda lokalize olan Xp22.1 geninin somatik mutasyonuna bağlı olarak ortaya çıkar. Bu defekte bağlı olarak, glikozil fosfatidil inositol (GFI) çapasının oluşumunda, bir defekt meydana gelir (3 Çalışmaya dahil edilen hiçbir hastada PNH klonu saptanmamıştır.…”