167
Views
16
CrossRef citations to date
0
Altmetric
Review

Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents

&
Pages 205-222 | Published online: 06 Jun 2008

References

  • AlfinitoFDel VecchioLRoccoS1996Blood cell flow cytometry in paroxysmal nocturnal hemoglobinuria: a tool for measuring the extent of the PNH cloneLeukemia101326308709638
  • AlmeidaAMMurakamiYBakerA2007Targeted therapy for inherited GPI deficiencyN Engl J Med3561641717442906
  • AlmeidaAMMurakamiYLaytonDM2006Hypomorphic promoter mutation in PIGM causes inherited glycosylphosphatidylinositol deficiencyNat Med128465116767100
  • AratenDJBesslerMMcKenzieS2002Dynamics of hematopoiesis in paroxysmal nocturnal hemoglobinuria (PNH): no evidence for intrinsic growth advantage of PNH clonesLeukemia162243812399968
  • AratenDJNafaKPakdeesuwanK1999Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individualsProc Natl Acad Sci USA9652091410220445
  • AratenDJSwirskyDKaradimitrisA2001Cytogenetic and morphological abnormalities in paroxysmal nocturnal haemoglobinuriaBr J Haematol115360811703336
  • AudebertHJPlanckJEisenburgM2005Cerebral ischemic infarction in paroxysmal nocturnal hemoglobinuria: report of 2 cases and updated review of 7 previously published patientsJ Neurol25213798616021362
  • BembaMGuardiolaPGarderetL1999Bone marrow transplantation for paroxysmal nocturnal haemoglobinuriaBr J Haematol105366810233405
  • BesslerMHillmenPLongoL1994Genomic organization of the X-linked gene (PIG-A) that is mutated in paroxysmal nocturnal haemoglobinuria and of a related autosomal pseudogene mapped to 12q21Hum Mol Genet375178081362
  • BoccuniPDel VecchioLDi NotoR2000Glycosyl phosphatidylinositol (GPI)-anchored molecules and the pathogenesis of paroxysmal nocturnal hemoglobinuriaCrit Rev Oncol Hematol33254310714960
  • BourantasK1994High-dose recombinant erythropoietin and low-dose corticosteroids for treatment of anemia in paroxysmal nocturnal hemoglobinuriaActa Haematol916258023644
  • BrodskyRAMukhinaGLLiS2000Improved detection and characterization of paroxysmal nocturnal hemoglobinuria using fluorescent aerolysinAm J Clin Pathol1144596610989647
  • BrodskyRAYoungNSAntonioliE2008Multicenter phase III study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuriaBlood1111840718055865
  • BurgeJNicholson-WellerAAustenKF1981Isolation of C4-binding protein from guinea pig plasma and demonstration of its function as a control protein of the classical complement pathway C3 convertaseJ Immunol12623256778916
  • CacciapuotiCTerrazzanoGBaroneL2007Glycosyl-phosphatidyl-inositol-defective granulocytes from paroxysmal nocturnal haemoglobinuria patients show increased bacterial ingestion but reduced respiratory burst inductionAm J Hematol829810717013814
  • ChenGZengWMaciejewskiJP2005Differential gene expression in hematopoietic progenitors from paroxysmal nocturnal hemoglobinuria patients reveals an apoptosis/immune response in ‘normal’ phenotype cellsLeukemia19862815759038
  • ChristmasSEde la Mata EspinosaCTHallidayD2006Levels of expression of complement regulatory proteins CD46, CD55 and CD59 on resting and activated human peripheral blood leucocytesImmunology119522816999828
  • DufourCCorcioneASvahnJ2001Interferon gamma and tumour necrosis factor alpha are overexpressed in bone marrow T lymphocytes from paediatric patients with aplastic anaemiaBr J Haematol11510233111843845
  • DunnDELiuJMYoungNS2000Paroxysmal nocturnal hemoglobinuriaYoungNSBone Marrow Failure SyndromesPhiladelphiaWB Saunders Company99121
  • EndoMWareREVreekeTM1996Molecular basis of the heterogeneity of expression of glycosyl phosphatidylinositol anchored proteins in paroxysmal nocturnal hemoglobinuriaBlood872546578630422
  • GargiuloLLastraioliSCerrutiG2007Highly homologous T-cell receptor beta sequences support a common target for autoreactive T cells in most patients with paroxysmal nocturnal hemoglobinuriaBlood10950364217284529
  • GoebelJForrestKFlynnD2002Lipid rafts, major histocompatibility complex molecules, and immune regulationHum Immunol638132012368033
  • HallCRichardsSHillmenP2003Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH)Blood10235879112893760
  • HarringtonWJSrKolodnyRHorstmannLL1997Danazol for paroxysmal nocturnal hemoglobinuriaAm J Hematol54149549034290
  • HauserACBrichtaAPabinger-FaschingI2003Fibrinolytic therapy with rt-PA in a patient with paroxysmal nocturnal hemoglobinuria and Budd-Chiari syndromeAnn Hematol8229930212707719
  • HertensteinBWagnerBBunjesD1995Emergence of CD52-, phosphatidylinositolglycan-anchor-deficient T lymphocytes after in vivo application of Campath-1H for refractory B-cell non-Hodgkin lymphomaBlood861487927632956
  • HillAHillmenPRichardsSJ2005aSustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuriaBlood10625596515985537
  • HillARidleySHEsserD2006Protection of erythrocytes from human complement-mediated lysis by membrane-targeted recombinant soluble CD59: a new approach to PNH therapyBlood1072131716322479
  • HillARotherRPHillmenP2005bImprovement in the symptoms of smooth muscle dystonia during eculizumab therapy in paroxysmal nocturnal hemoglobinuriaHaematologica90ECR4016464755
  • HillARichardsSJHillmenP2007aRecent developments in the understanding and management of paroxysmal nocturnal haemoglobinuriaBr J Haematol1371819217408457
  • HillARichardsSJRotherRP2007bErythopoietin treatment during complement inhibition with eculizumab in a patient with paroxysmal nocturnal hemoglobinuriaHaematologica92ECR14
  • HillmenPHallCMarshJC2004Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuriaN Engl J Med350552914762182
  • HillmenPLewisSMBesslerM1995Natural history of paroxysmal nocturnal hemoglobinuriaN Engl J Med333125387566002
  • HillmenPMuusPDuhrsenU2007Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuriaBlood1104123817702897
  • HillmenPYoungNSSchubertJ2006The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuriaN Engl J Med35512334316990386
  • HiroseSRaviLPrinceGM1992Synthesis of mannosylglucos-aminylinositol phospholipids in normal but not paroxysmal nocturnal hemoglobinuria cellsProc Natl Acad Sci USA89602591378620
  • HolguinMHWilcoxLABernshawNJ1989Relationship between the membrane inhibitor of reactive lysis and the erythrocyte phenotypes of paroxysmal nocturnal hemoglobinuriaJ Clin Invest841387942478585
  • HuRMukhinaGLPiantadosiS2005PIG-A mutations in normal hematopoiesisBlood10538485415687243
  • HugelBSociéGVuT1999Elevated levels of circulating procoagulant microparticles in patients with paroxysmal nocturnal hemoglobinuria and aplastic anemiaBlood933451610233897
  • IssaragrisilSPiankijagumATang.NaitrisoranaYCorticosteroid therapy in paroxysmal nocturnal hemoglobinuriaAm J Hematol2577833578265
  • JasinskiMKellerPFujiwaraY2001GATA1-Cre mediates Piga gene inactivation in the erythroid/megakaryocytic lineage and leads to circulating red cells with a partial deficiency in glycosyl phosphatidylinositol-linked proteins (paroxysmal nocturnal hemoglobinuria type II cells)Blood9822485511568013
  • KaradimitrisAManavalanJSThalerHT2000Abnormal T-cell repertoire is consistent with immune process underlying the pathogenesis of paroxysmal nocturnal hemoglobinuriaBlood9626132011001919
  • KatayamaYHiramatsuYKohriyamaH2001Monitoring of CD59 expression in paroxysmal nocturnal hemoglobinuria treated with danazolAm J Hematol68280311754418
  • KellerPPayneJLTremmlG2001FES-Cre targets phosphatidylinositol glycan class A (PIGA) inactivation to hematopoietic stem cells in the bone marrowJ Exp Med194581911535627
  • KookHRisitanoAMZengW2002Changes in T-cell receptor VB repertoire in aplastic anemia: effects of different immunosuppressive regimensBlood9936687511986222
  • LuzzattoLBesslerM1996The dual pathogenesis of paroxysmal nocturnal hemoglobinuriaCurr Opin Hematol3101109372059
  • LuzzattoLBesslerMRotoliB1997Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise?Cell88149019395
  • MaciejewskiJPSloandEMSatoT1997Impaired hematopoiesis in paroxysmal nocturnal hemoglobinuria/aplastic anemia is not associated with a selective proliferative defect in the glycosylphosphatidylinositol-anchored protein-deficient cloneBlood891173819028939
  • MahoneyJFUrakazeMHallS1992Defective glycosylphosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria granulocytesBlood79140031372185
  • MatisLARollinsSA1995Complement-specific antibodies: designing novel anti-inflammatoriesNat Med1839427585191
  • McMullinMFHillmenPElderGE1996Serum erythropoietin level in paroxysmal nocturnal hemoglobinuria: implications for therapyBr J Haematol9281578616071
  • McMullinMFHillmenPJacksonJ1994Tissue plasminogen activator for hepatic vein thrombosis in paroxysmal nocturnal haemoglobinuriaJ Intern Med2358598283166
  • MedofMEKinoshitaTNussenzweigV1984Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranesJ Exp Med1601558786238120
  • MiyataTTakedaJIidaY1993The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesisScience2591318207680492
  • MoyoVMMukhinaGLGarrettES2004Natural history of paroxysmal nocturnal haemoglobinuria using modern diagnostic assaysBr J Haematol126133815198744
  • MurakamiYKosakaHMaedaY2002Inefficient response of T lymphocytes to glycosylphosphatidylinositol anchor-negative cells: implications for paroxysmal nocturnal hemoglobinuriaBlood10041162212393537
  • NafaKBesslerMDeegHJ1998New somatic mutation in the PIG-A gene emerges at relapse of paroxysmal nocturnal hemoglobinuriaBlood92342279787183
  • NafaKBesslerMMasonP1996Factor V Leiden mutation investigated by amplification created restriction enzyme site (ACRES) in PNH patients with and without thrombosisHaematologica8154029009443
  • NagakuraSIshiharaSDunnDE2002Decreased susceptibility of leukemic cells with PIG-A mutation to natural killer cells in vitroBlood1001031712130519
  • NakaoSTakamiATakamatsuH1997Isolation of a T-cell clone showing HLA-DRB1*0405-restricted cytotoxicity for hematopoietic cells in a patient with aplastic anemiaBlood89369199160674
  • Nicholson-WellerAMarchJPRosenfeldSI1983Affected erythrocytes of patients with paroxysmal nocturnal hemoglobinuria are deficient in the complement regulatory protein, decay accelerating factorProc Natl Acad Sci USA805066706576376
  • Nicholson-WellerASpicerDBAustenKF1985Deficiency of the complement regulatory protein, “decay-accelerating factor,” on membranes of granulocytes, monocytes, and platelets in paroxysmal nocturnal hemoglobinuriaN Engl J Med312109173845321
  • NinomiyaHHasegawaYNagasawaT1997Excess soluble urokinase-type plasminogen activator receptor in the plasma of patients with paroxysmal nocturnal hemoglobinuria inhibits cell-associated fibrinolytic activityInt J Hematol65285919114600
  • Nishimura JiJHirotaTKanakuraY2002Long-term support of hematopoiesis by a single stem cell clone in patients with paroxysmal nocturnal hemoglobinuriaBlood9927485111929762
  • NishimuraJKanakuraYWareRE2004Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and JapanMedicine (Baltimore)8319320715118546
  • OkadaNHaradaROkadaH1990Erythrocytes of patients with paroxysmal nocturnal haemoglobinuria acquire resistance to complement attack by purified 20-kD homologous restriction factorClin Exp Immunol80109131691059
  • OlsenSBTangDBJacksonMR1996Enhancement of platelet deposition by cross-linked hemoglobin in a rat carotid endarterectomy modelCirculation93327328548906
  • OniBSOsunkoyaBOLuzzattoL1970Paroxysmal nocturnal hemoglobinuria: evidence for monoclonal origin of abnormal red cellsBlood36145525448520
  • ParkerCOmineMRichardsSInternational PNH Interest Group2005Diagnosis and management of paroxysmal nocturnal hemoglobinuriaBlood106369970916051736
  • Peffault de LatourRMaryJYSalanoubatC2006Paroxysmal Nocturnal Hemoglobinuria (PNH): Long-Term Epidemiological StudyBlood108291a
  • PlasilovaMRisitanoAMaciejewskiJP2003Application of the molecular analysis of the T-cell receptor repertoire in the study of immune-mediated hematologic diseasesHematology81738112745651
  • PlasilovaMRisitanoAMO’KeefeCL2004Shared and individual specificities of immunodominant cytotoxic T cell clones in Paroxysmal Nocturnal Hemoglobinuria as determined by molecular analysisExp Hematol32261915003311
  • PoggiANegriniSZocchiMR2005Patients with paroxysmal nocturnal hemoglobinuria have a high frequency of peripheral-blood T cells expressing activating isoforms of inhibiting superfamily receptorsBlood106239940815956278
  • PramoonjagoPPakdeesuwanKSiripanyaphinyoU1999Genotypic, immunophenotypic and clinical features of Thai patients with paroxysmal nocturnal haemoglobinuriaBr J Haematol10549750410233427
  • RaiolaAMVan LintMTLamparelliT2000Bone marrow transplantation for paroxysmal nocturnal hemoglobinuriaHaematologica85596210629593
  • RichardsSJRawstronACHillmenP2000Application of flow cytometry to the diagnosis of paroxysmal nocturnal hemoglobinuriaCytometry422233310934341
  • RisitanoAMHillARicciP2007Paroxysmal nocturnal hemoglobinuria (PNH) in the eculizumab era: the bedside and beyondHaematologica92s389a
  • RisitanoAMHillmenPBarbanoF2006The complement inhibitor eculizumab to treat paroxysmal nocturnal hemoglobinuria patients: a single center experience within the Triumph, Shepherd and Extension studiesHaematologica91s3135a
  • RisitanoAMKookHZengW2002Oligoclonal and polyclonal CD4 and CD8 lymphocytes in aplastic anemia and paroxysmal nocturnal hemoglobinuria measured by Vβ CDR3 spectratyping and flow cytometryBlood1001788312070025
  • RisitanoAMMaciejewskiJPGreenS2004In vivo dominant immune responses in aplastic anemia patients: molecular tracking of putatively pathogenic T cells by TCRβ-CDR3 sequencingLancet36435363
  • RisitanoAMMaciejewskiJPMuranskiP2005Large granular lymphocyte (LGL)-like clonal expansions in paroxysmal nocturnal hemoglobinuria (PNH) patientsLeukemia192172215668701
  • RosenfeldSIJenkinsDEJrLeddyJP1985Enhanced reactive lysis of paroxysmal nocturnal hemoglobinuria erythrocytes by C5b-9 does not involve increased C7 binding or cell-bound C3bJ Immunol134506113964820
  • RosseWF1982Treatment of paroxysmal nocturnal hemoglobinuriaBlood602037044450
  • RosseWF1990Phosphatidylinositol-linked proteins and paroxysmal nocturnal hemoglobinuriaBlood7515956012183885
  • RosseWF1996Epidemiology of PNHLancet34857378774569
  • RosseWFDacieJV1966Immune lysis of normal human and paroxysmal nocturnal hemoglobinuria (PNH) red blood cells. I. The sensitivity of PNH red cells to lysis by complement and specific antibodyJ Clin Invest45736485935361
  • RostiVTremmlGSoaresV1997Murine embryonic stem cells without pig-a gene activity are competent for hematopoiesis with the PNH phenotype but not for clonal expansionJ Clin Invest1001028369276719
  • RotherRPBellLHillmenP2005The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human diseaseJAMA29316536215811985
  • RotherRPRollinsSAMojcikCF2007Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuriaNat Biotechnol2512566417989688
  • RotoliBBesslerMAlfinitoF1993Membrane proteins in paroxysmal nocturnal haemoglobinuriaBlood Rev775868369662
  • RotoliBLuzzattoL1989Paroxysmal nocturnal haemoglobinuriaBaillieres Clin Haematol2113382645958
  • RotoliBRobledoRLuzzattoL1982Decreased number of circulating BFU-Es in paroxysmal nocturnal hemoglobinuriaBlood6015797082835
  • RotoliBRobledoRScarpatoN1984Two populations of erythroid cell progenitors in paroxysmal nocturnal hemoglobinuriaBlood64847516478058
  • RotoliBNafaDRisitanoAM2006Paroxysmal nocturnal hemoglobinuriaRungeMDPattersonCPrinciples of Molecolar Medicine2nd editionPhiladelphiaHumana Press83847
  • Sanchez-ValleEMorales-PolancoMRGomez-MoralesE1993Treatment of paroxysmal nocturnal hemoglobinuria with antilymphocyte globulinRev Invest Clin45457618134727
  • SantaroneSDi BartolomeoEBacigalupo2008Long-term results of a GITMO retrospective study on haematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuraBone Marrow Transplant41S11917934531
  • SasoRMarshJCevreskaL1999Bone marrow transplants for paroxysmal nocturnal haemoglobinuriaBr J Haematol104392610050724
  • SatoTSelleriCAndersonS1997Expression and modulation of cellular receptors for interferon-gamma, tumour necrosis factor, and Fas on human bone marrow CD34+ cellsBr J Haematol97356659163602
  • SchaferAWiesmannFNeubauerS2004Rapid regulation of platelet activation in vivo by nitric oxideCirculation10918192215066953
  • SelvarajPRosseWFSilberR1988The major Fc receptor in blood has a phosphatidylinositol anchor and is deficient in paroxysmal nocturnal haemoglobinuriaNature33356572967435
  • ShichishimaTSaitohYTerasawaT1999Complement sensitivity of erythrocytes in a patient with inherited complete deficiency of CD59 or with the Inab phenotypeBr J Haematol104303610050712
  • ShinMLHänschGHuVW1986Membrane factors responsible for homologous species restriction of complement-mediated lysis: evidence for a factor other than DAF operating at the stage of C8 and C9J Immunol1361777822419414
  • SimakJHoladaKRisitanoAM2004Elevated counts of circulating endothelial membrane microparticles in paroxysmal nocturnal hemoglobinuria indicate inflammatory status and ongoing stimulation of vascular endotheliumBr J Hemat12580413
  • SloandEMaciejewskiJPTisdaleJ2002Intracellular Interferon-γ (IFN-γ) in circulating and marrow T cells detected by flow cytometry and the response to immunosuppressive therapy in patients with aplastic anemiaBlood10031293511964274
  • SloandEMMoreKShahS2006Soluble urokinase plasminogen activator receptor is increased in patients with paroxysmal nocturnal hemoglobinuria (PNH) and thrombosis and inhibits plasmin generation in vitro and promotes thrombosis in the mouse modelBlood108422a
  • SocieGMaryJYde GramontA1996Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of HaematologyLancet34857378774569
  • SteblerCTichelliADazziH1990High-dose recombinant human erythropoietin for treatment of anemia in myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria: a pilot studyExp Hematol18120482226680
  • SutherlandDRKuekNDavidsonJ2007Diagnosing PNH with FLAER and multiparameter flow cytometryCytometry B Clin Cytom721677717285629
  • TakahashiMTakedaJHiroseS1993Deficient biosynthesis of N-acetylglucosaminyl-phosphatidylinositol, the first intermediate of glycosyl phosphatidylinositol anchor biosynthesis, in cell lines established from patients with paroxysmal nocturnal hemoglobinuriaJ Exp Med177517218426120
  • TakedaJMiyataTKawagoeK1992Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuriaCell73703118500164
  • TichelliAGratwohlANissenC1992Morphology in patients with severe aplastic anemia treated with antilymphocyte globulinBlood80337451627795
  • van der SchootCEHuizingaTWvan ‘t Veer-KorthofET1990Deficiency of glycosylphosphatidylinositol-linked membrane glycoproteins of leukocytes in paroxysmal nocturnal hemoglobinuria, description of a new diagnostic cytofluorometric assayBlood76185392145990
  • WiedmerTHallSEOrtelTL1993Complement-induced vesiculation and exposure of membrane prothrombinase sites in platelets of paroxysmal nocturnal hemoglobinuriaBlood82119267688991
  • WilcoxLAEzzellJLBernshawNJ1991Molecular basis of the enhanced susceptibility of the erythrocytes of paroxysmal nocturnal hemoglobinuria to hemolysis in acidified serumBlood7882091713516
  • YamashinaMUedaEKinoshitaT1990Inherited complete deficiency of 20-kilodalton homologous restriction factor (CD59) as a cause of paroxysmal nocturnal hemoglobinuriaN Engl J Med323118491699124
  • YoungNSMaciejewskiJP2000Genetic and environmental effects in paroxysmal nocturnal hemoglobinuria: this little PIG-A goes “Why? Why? Why?”J Clin Invest1066374110974016
  • ZalmanLSWoodLMMüller-EberhardHJ1986Isolation of a human erythrocyte membrane protein capable of inhibiting expression of homologous complement transmembrane channelsProc Natl Acad Sci USA83697592428045
  • ZalmanLSWoodLMFrankMM1987Deficiency of the homologous restriction factor in paroxysmal nocturnal hemoglobinuriaJ Exp Med16557272434597
  • ZengWMaciejewskiJPChenG2001Limited heterogeneity of T-cell receptor VB usage in aplastic anemiaJ Clin Invest1087657311544283
  • ZoumbosNGasconPTrostS1985Circulating activated suppressor T lymphocytes in aplastic anemiaN Engl J Med312257652981406

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.