title: Paroxysmal nocturnal haemoglobinuria: diagnostic tests, advantages, & limitations.
abstract: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired clonal disorder of haematopoietic stem cells. The molecular defect in PNH is mutation in the phosphotidylinositol glycan complementation class A (PIGA gene) causing defect in glycosylphosphatidylinositol anchored proteins (Cell, 73, 1993, 703). The deficiency of these GPI-anchored proteins on the membranes of haematopoietic cells lead to the various clinical manifestations of PNH. Clinically PNH is classified into classic PNH, PNH in the setting of another specified bone marrow disorder and sub clinical PNH. Size of the PNH clone differs in these different subtypes. The management of PNH has been revolutionized by the advent of monoclonal antibody, eculizumab. Thus, today it is important to have sensitive tests to diagnose and monitor the clone size in patients of PNH. Before 1990, diagnosis of PNH was made using complement based tests. However in the last decade, flowcytometry has become the gold standard diagnostic test as it has increased sensitivity to detect small clones, ability to measure clone size and is not affected by blood transfusions. This review is aimed to focus mainly on the different methods available for the detection of PNH clone and the recent advances and recommendations for the flowcytometric diagnosis of PNH.
authors.affiliation: National Institute of Immunohaematology, KEM Hospital, Parel, Mumbai, India. madkaikarm@icmr.org.in
authors.forename: Manisha
authors.initials: M
authors.lastname: Madkaikar
authors.forename: Maya
authors.initials: M
authors.lastname: Gupta
authors.forename: Farah
authors.initials: F
authors.lastname: Jijina
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
mesh_terms: D001856:Bone Marrow Examination; D018958:CD55 Antigens / Q000032:analysis; D018957:CD59 Antigens / Q000032:analysis; D002469:Cell Separation / Q000379:methods*; D048429:Cell Size; D002999:Clone Cells / Q000473:pathology; D015941:Complement Hemolytic Activity Assay; D004912:Erythrocytes / Q000737:chemistry / Q000648:ultrastructure; D005434:Flow Cytometry / Q000379:methods*; D005456:Fluorescent Dyes / Q000032:analysis; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006386:Hemagglutination Tests; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000145:classification / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping / Q000592:standards; D007962:Leukocytes / Q000737:chemistry / Q000648:ultrastructure; D008565:Membrane Proteins / Q000032:analysis / Q000172:deficiency / Q000235:genetics; D009391:Nephelometry and Turbidimetry / Q000592:standards; D012680:Sensitivity and Specificity; D019851:Thrombophilia / Q000097:blood / Q000209:etiology
chemical_list: D018958:CD55 Antigens; D018957:CD59 Antigens; D005456:Fluorescent Dyes; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein; C051590:CD59 protein, human