输血过滤器的临床应用.ppt

输血过滤器的临床应用陈育新 MilitaryAircraftEngineIntakeAir RoyalNavySeaKingHelicopterfilteredbyPALLFiltration 1 2 30 LeoYangPallTWNSciences WelcometoPallCorporation PallisAllAroundYou Ensuringthepurityandclarityofthewine beerandwateryoudrink PallisAllAroundYou Helpingtomakevaccinespureandsafe ACultureofInnovation 1946DrPallinventsporousstainlesssteelandfoundsthecompanythatwillbecomePallCorporation 1958Pall sFiltersprovideprotectionforhydraulicsystemsonJupiterCbooster 1959Rigimesh filtermediaisdevelopedbyPallfortheprotectionofBoeing707hydraulicsystems 1969PalldevelopsaspacesuitheatexchangerandlunarmodulefiltrationfortheApollo11mission 1971BloodfiltersbasedonthePallUltipor filtermediaareintroducedtoprotectcardiacpatientsfrommicroemboli improvingpostoperativeoutcomes ACultureofInnovation 1979PMM filtermediaisdevelopedasaclean upsolutionforThreeMileIslandsite 1988Pallintroducesitsleukoreductionfilterstocombatpost transfusionfeverandallergicreactions 1989Pall sScientificandLaboratoryServicesdevelopsfiltrationandmaintenancestandardsforhydraulicssystemsontheEurotunnelboringmachines ensuringreliableoperationunderchallengingenvironmentalconditions 1990Dr PallisawardedtheNationalMedalofTechnologybyPresidentGeorgeBushSr ACultureofInnovation 1991ThePallCentriSep Systemprovidesinnovativeprotectionforthemilitary sintakesystemsinharshconditionsduringoperation DesertStorm 1993TheBB25breathingcircuitfilter developedbyPalltopreventcontaminationofventilatingequipment ItbecomescriticallyimportantinfightingthespreadofSARSandAvianFlu 1995PallCorporationintroducestheDV50 thefirstvalidatedvirus retentioncartridgefilterforthepharmaceuticalindustry 2006Pall sAcrodose PLSystemisintroducedtoincreasethesafetyandavailabilityoflife savingplatelets TomorrowPallproductswillcontinuetoprotectmissioncriticalsystemsineventheharshestenvironments FiltersUsedforBloodComponentsAdministration TypeofFilterRemovalCharacteristicClotScreenPoresizeof170umMicroaggregatePoresizeof2040umLeukocyteremovalRateontheefficiencyofleukocyteremove notbyporesize BLOODFILTRATIONTECHNOLOGYMicroaggregateLeucocytereductionredcellsplateletssalvagedbloodBloodbankfiltersBedside hospital filters Transfusion AssociatedLeukocyte MediatedMorbidity WalkerJH AmerJClinPath88 374 8 1987 FrequencyofOccurrence Dose ResponseforTransfusionandInfection Patientstransfusedwith1to4unitshaveinfectiouscomplicationsratesapproaching20 Dose ResponseRelationshipAllogeneicTransfusionandInfection Asingletransfusedunithasbeencorrelatedwithsignificantlyincreasedinfectiouscomplicationsapproximating15 CLINICALEFFECTSOFCONTAMINATINGLEUCOCYTES HLAAlloimmunisationReactionsPlateletGraftRefractorinessRejectionViralTransmissionCytomegalovirus CMV EBV HTLVI II VaricellazosterImmuneSuppressionPostCancerLatentOperativeRecurrenceViralInfectionReactivation ContaminatingLeucocytes KnowneffectsofLeucocytes Alloimmunization leadingontoRefractorinessInfectiontransmission virusesandbacteriaImmuno modulation higherincidenceofpostop InfectionImmuno suppression higherANDincreasedincidenceofsolidtumourreformation ALLOIMMUNISATIONANDREFRACTORINESS AntigenPresentingCell B Lymphocyte PlasmaCell MemoryCell T Lymphocyte Donor Recipient Transfusion YYYY YYY YYY YY YYYY YYYY AntibodyProduction TheproductionofHLAantibodiesisa2signalprocessrequiringthepresenceofbothClassIandClassIIantigensLocationofHLA HLAClassIPresentonALLnucleatedcells whitecells andplatelets HLAClassIIPresentONLYonMonocytes Macrophages B Lymphocytes activatedT Lymphocytes dendriticcellsNB redcellsdonotexpressHLA Alloimmunisation ALLOIMMUNISATION ControlGroupsFilterGroups ANALYSISOFUTILIZATIONANDCOSTOFPLATELETTRANSFUSIONINREFRACTORYHEMATOLOGY ONCOLOGYPATIENTS NumberofAveragePlateletsAverageAdmissionsTransfusedPlateletCosts Lilletal A S H 1997 82 Authorsfoundadditionalcostsavingsintermsoflengthofhospitalstay 23 41 reduction andtotalcharges 10 41 reduction intheleucocytedepletedarm 造成血小板减少的病人出血之原因 除了血小板数目外 很多其它的临床症状也要考虑 例如败血症 尿毒症 凝血功能异常 以及药物的影响等 不之疾病造成血小板之减少症 对输血小板之反应不尽相同 如败血症 脾肿大 免疫性血小板减少症 则对输血小板之反应不佳 因此 除了血小板的数目外 引起血小板减少之原因及疾病亦应注意 才能掌握血小板输注的正确时效 治疗性血小板输注呢 一般而言 是只对正在出血的血小板减少之病人之治疗方法 这时在输血小板之前及之后 对血中血小板数量的监测与比较是很重要的 因为这样可以评估血小板的存活数量 以及预测未来对输血小板的需求 如果血小板的数量没有爬升 即使是反覆的输血 可能对病人并没有什么好处 通常此时医师必须积极去追查造成顽固性血小板减少的原因 有一些疾病所导致的血小板减少症对输血小板的反应良好 特别是针对骨髓抑制所造成的顽固性血小版减少症 如化学治疗后 放射线治疗后 维持生活素缺乏 或是再生性不良性贫血等 另外有一些疾病所导致的血小板减少症则对输血小板反应不好 如 败血症 sepsis 脾脏肿大 splenectomy 以及免疫性血小板减少症 包括自体免疫性血小板减少症 immunethrombocytopenia 药物引起之血小板减少症 或是淋巴增生性疾病等 相对的 有一些疾病所导致的血小板减少症 输血小板则为其禁忌症 如血栓性血小板减少性紫斑症 thromboticthrombocytopenicpurpura 可能会因输血小板而导致血栓更加恶化 顽固性 refractory 的血小板减少症 顽固性 refractory 的血小板减少症包含了 1 非免疫性 non immune 的顽固性的血小板减少症2 异体免疫性 alloimmunization 的顽固性的血小板减少症非免疫性的顽固性血小板减少症的原因包含 败血症 sepsis 弥漫性血管内凝血症 DIC 以及脾脏肿大 splenomegaly 等 对于非免疫性的顽固性的血小板减少症的处理方法有 1 使用ABO血型相符之血品2 使用新鲜血小板3 在脾脏肿大 splenectomy 的病人则应增加血小板的剂量4 治疗败血症 sepsis 及弥漫性血管内凝血症 DIC 的原因5 考虑使用单一捐赠者HLA相符之血小板等 异体免疫性的顽固性血小板减少症根据统计 约有20 至70 反覆输血小板患者会产生异体抗体 allo antibody 一般发生在输血小板两个月内 有少数的病人于输血小板前即有异体抗体 allo antibody 多半是因为从前曾输血小板或怀孕的缘故 90 的异体抗体 allo antibody 与HLA typing有关 血小板只有携带第一型 classI HLA抗原 血小板本身并不足以对这些抗原引发原发性免疫性免疫反应 但是白血球同时携带第一型 classI 及第二型 classII HLA抗原 足以引发异体免疫 alloimmunization 反应 一但白血球引发原发性异体免疫反应 primaryalloimmunization 血小板亦引发次发性异体免疫反应 secondaryalloimmunization 使用类固醇 steroid 或脾藏切除 splenectomy 对处理具异体免疫抗体患者的效果不好 而使用IVIG亦只有对少数患者有效 减少捐赠者的人数并没有减少异体免疫抗体产生的机会 即便是仅使用单一捐赠者输血小板 亦只有少数研究报告显示有统计上的差异 脾切除 脾切除对自体免疫性血小板减少症及脾功能过盛之病人亦为一很好之治疗方法 根据我们最进之统计资料约有70 脾切除后之自体免疫性血小板减少之病人 不必服药而其小血小板有明显之升高至正常护接近正常之现象 临床上红血球抗体的发生 与红血球抗原的致免疫性 immunogenecity 或称抗原性 有关 当然 致免疫性之高低 虽然主要是因抗原不同而异 但免疫途径 免疫方法及频率也有所影响 宿主本身的免疫力和身体状况更是影响抗体发生的重大因素 红血球抗原的致免疫性以Rh D 抗原最强 K抗原其次 其大致的致免疫性如下 以一次输血后会发生抗体的频率表示 Non hemolyticfebriletransfusionreactions AlloimmunizationPost transfusionthrombocytopeniaCytomegalovirustransmissionTransfusioninducedimmunosuppression infection cancerrecurrence ReductionoftheriskofnvCJDtransmission LeukocyteDepletionofHomologousBloodProducts Redcells platelets plasma BarrierRetentionandPoreSize SCREENFILTRATIONScreens20 40um 40ummostcommon Absolutefilters LargesurfaceareaifmembraneispleatedNormallymadeofpolyester DEPTHFILTRATIONVariableporesizeremovalefficiencyofparticles airdependantondensityLowsurfacearea Modifiedpolyesters adsorbleukocytes WHENTOFILTER THELOGISTICS Filter DonationHoldProcessingStorageTransfusion WarmBlood VariableTemperature ControlledTemperature Non HemolyticFebrileTransfusionReactions Residualleukocytecount 109 1 00 5 0 2 0 1 0 05 Patientreactionrate Sirchi Transfusion30 30 33 1990 PreventionofNHFTRofthalassemiapatienttreatedwithmultiplebloodtransfusion FactorsofPlateletRefractoriness MajorFactorsInfluencingtheCorrectedCountIncrementNon Immune 1 Splenomegaly2 DisseminateIntravascularCoagulation DIC 3 Drugs NumberofAntibacterialsandAmphotercinB 4 Sepsis Infection5 FeverImmune 1 Platelet SpecificAntibody2 HLA Antibody Alloimmunization TrialtoReduceAlloimmuizationtoPlateletsTRAPStudyNewEnglJMed 337 1861 1869 T R A P StudyResultsRateofAlloimmuneRefractoriness Verylowincidenceofrefractoriness Allarmsareequallyeffectiveinreducingtheincidenceofalloimmunerefractoriness ThereisnoadditionalbenefitofusingfilteredSDplateletscomparedtopooledPC plateletconcentrates preventingalloimmunerefractoriness T R A P StudyResultsConclusions PlateletTransfusion SDP RDP A Thomas M D EconomicRoadmapstoUniversalLeukocyteReduction 99 PallProgram AABB ROLEOFBLOODTRANSFUSIONINCMVTRANSMISSIONANDREACTIVATION CMV PRIMARYINFECTIONegBloodTransfusion REINFECTION2ndStrainIntroducedinBloodTransfusion REACTIVATIONegImmunosuppression LeukocyteReductionComparabletoCMVSeronegativeBlood BowdenRAetal Transfusion 1995 35 719 722 Aprospective randomizedtrial520CMVseronegativemarrowrecipients ScreenedBlood N 252FilteredBlood N 250Betweendays21and100aftertransplant patientsweremonitoredforthedevelopmentofCMVinfectionandtissue documentedCMVdisease LeukocyteReductionComparabletoCMVSeronegativeBlood TransfusionTreatment P 0 05SeronegativevsUnscreenedFiltered BowdenRAetal Transfusion 1995 35 719 722 Transfusioninducedimmunosuppression infection AdaptedfromJensenetal Lancet1996 348 841 845 InfectionRate orReoperation ReducesWoundInfection PneumoniaandReoperation TransfusionRegimen 141185 DaysinHospital Dollars thousands Cost EffectivenessofLeukoreduction TransfusionRegimen AdaptedfromJensenetal Transfusion1995 35 719 722 TheRoadtoUniversalLeukocyteReduction AmericanRedCrossBPACPublicStatements TheAmericanRedCrosswillpresentthefollowingviewsattheFoodandDrugAdministrationBloodProductsAdvisoryCommittee BPAC meetingtodayandFriday TheBPACadvisestheFDAonavarietyofissuesthatpertaintobloodproducts fromrecommendingapprovalofnewproductstorecommendingchangesofregulations Itisstrictlyanadvisorycommittee Thisinformationmayappearsomewhattechnical however itinvolvesRedCorsspolicyonfimprovedtestingforinfectiousagentstoimprovethesafetyofAmerica sbloodsupply AABB sAssociationBulletin 97 2 LimitationsintheInterpretationoftheAboveData Manyoftheearlystudiescouldnothavebeenanaccurateassessmentofresidualleukocytecountsinthecomponentsadministered Thefocusatthattimewasonpercentleukocytereduction Inaddition manyofthestudiesdidnothaveappropriatecontrolgroups norweretheyrandomized Inadditiontotheproblemofprimaryvssecondaryanalyses thefinalpapernotedabovelacksanintent to treaanalysis andcontainsprotocolandtypographicalerrors Nevertheless thislargerandomizedtrialappearstodocumentthatwhenaparticularmanufacturer sfilterswereusedatthebedsideundertheconditionsdeterminedbythestudyprotocol resultswereequivalenttotheuseofseronegativedonorblood Fromtheavailabledataitcannotbedeterminedwhethersuchresultswouldbeobtainedoutsidethesettingofacontrolledclinicaltrial withtheuseofothermanufacturers componentsorwiththeuseofotherleukocytereductiontechnologies Recentstudies infact havesuggestedthattheperformanceofbedsidefiltrationofredcellconcentratesmaybesuboptimalcomparedtofiltrationunderlaboratoryconditions StudiesbyLedentandSirchiahaveprovidedin vitroevidencethatslowfiltrationaroomtemperature asoccursinabedsidesetting allowswarmingofredcellconcentratesandsubsequentsuboptimalremovalofdonorleukocytes Hospitaltransfusionservicesshouldcontinuetoreevaluatethemostappropriateapplicationofleukocytereductiontechnologyinlightofongoingresearch byKarenShoosLipton JD ChiefExecutiveOfficer AABB sAssociationBulletin 97 2 Continuous ExpectationofaLowIncidenceofTT CMVFollowingTransfusionofLeukocyte ReducedComponents Itispossiblethatnormalblooddonorscanhaveatransientandepisodicviremia Possiblyduetoadecreaseintheregulatorycontroloverthelatentinfection Thisconceptisunproven andtheincidenceandkineticsoftheviremiahavenotbeenstudied Unpublisheddata Hillyer CD ontheuseofPCRhaveconfirmedthatfreeplasmawilltransmitCMVdespitetheuseofcurrentleukocytereductionfilters Additionally thedegreeofleukocytereductionnecessarytodecreasetheriskofTT CMVhadnotbeendetermined Thus itispossiblethatsomeleukocyte reducedcomponentsmaytransmitCMV Inaddition clinicianswhorelyexclusivelyontheuseofantibodyrestingtomakethediagnosisofCMVmustrecognizethattheuseofCMV untestedleukocyte reducedbloodmayresultinthepassivetransferofdonorantibodiestoCMV whichcouldcomplicatethediagnosisofCMVinfectionsinpatients byKarenShoosLipton JD ChiefExecutiveOfficer CONCLUSION ThedataconfirmthatdistinctphenotypicdifferencesexistamongPCspreparedwithdifferentdevicesand orprocedures Itissuggestedthatasfornon genericpharmaceuticals theclinicalbenefitsofthesevariousPCsshouldbeindividuallyproved TRANSFUSIONVolume38 July1998 WhitecellsubsetsinapheresisandfilteredplateletconcentratesS O Sowemimo Coker A Kim E Tribble H J Brandwein andB Wenz TRANSFUSIONVolume38 July1998 Whitecellsubsetsinapheresisandfilteredplateletconcentrates Continuous TRANSFUSIONVolume38 July1998 Whitecellsubsetsinapheresisandfilteredplateletconcentrates Continuous FunctionsofLeukocyteSubsets Monocytes MajorAntigenPresentingCells whichareabletoinitiateimmunereactionsleadingtoalloimmunization Granulocytes Phagocyticcellswhichengulfanddestroyforeignmatter Mainlyresponsibleforfebriletransfusionreactions Evidencesuggeststhatcytomegalovirus CMV maybespecifictogranulocytes althoughmonocytesmayalsoharborCMV Lymphocytes Carryoutavarietyofimmunefunctions Mainreservoirforcellassociatedretroviruses BLymphocytes CommittedBlymphocytesproduceandsecreteantibodies IgG IgM Majorantigenpresentingcellsresponsibleforalloimmunization FunctionsofLeukocyteSubsets Continuous T4 Lymphocytes TcellshavingCD4phenotypeplaykey helper roleinregulatingtheimmuneresponsebyvirtueoftheirabilitytodirect B cellstodifferentiateandproduceantibodies directactivationofCD8positivecytotoxiceffectorcells activatemacrophagesandNaturalKillerCells NK andalsodirectthegenerationofCD8 positivesuppressorcells T8 Lymphocytes TcellshavingCD8phenotypescandevelopintoT suppressorcells thatalsoplayanimportantroleinmodulatingtheproductionofantibodiesbyBlymphocytes andalsoT Cytotoxiccellswhichareimportantinthedefenseagainstviruses NaturalKillerCells LymphoidcellsthataredistinctfromTandBlymphocytesandareimportantintransplantationrejectionandeliminationofmalignanttumors 主旨NH F TR发生的概率并无法因Prestorage之白血球过滤处理而具有任何统计上意义之降低 目前一系列新的证据显示 使用乏白血球处理后之血小板 能使NH F TR发生比率再降低之关键并非以Prestorage方式去白血球可以降低之Cytokine 而在血小板本身产生之ChemokineRANTES系列 说明请参考后附之 Transfusion1999 39 1179 1184 期刊所发表之论文 在该篇论文中详细记录 统计 分析了1992 1996年间 德国血液及肿瘤科因化疗或脊髓功能不健全而造成血小板缺乏症而需输血小板患者之所有输血反应之记录 其二组对照比较之情况 均用PALLFilter 如表一 Febrileandallergictransfusionreactionsafterthetransfusionofwhitecell poorplateletpreparationsH Kluter S Bubel H Kirchner andD Wilhelm CONCLUSION PrestorageWBCfiltrationdidnotreducetheincidenceofthesereactions andinflammatorycytokineswereofminorrelevance Theproinflammatoryplatelet derivedchemokineRANTES whichaccumulateseveninWBC reducedplateletconcentrates wasassociatedwithallergictransfusionreactions Platelet derivedmediatorsmaybeakeytounderstandingNHTRs TRANSFUSIONVolume39 November December1999 Febrileandallergictransfusionreactionsafterthetransfusionofwhitecell poorplateletpreparations Continuous Nonhemolytictransfusionreactions NHTRs arecommonsideeffectsafterthetransfusionofbloodcomponents Mostofthereactionsaremild butsomearelife threatening becauseofsevereanaphylacticshock Whereasinthepastwhitecell WBC antibodieswereofforemostrelevance theirimpactfadedwiththeintroductionofWBC reductiondevices Recently contaminatinginflammatorycytokinesinplateletconcentrates PCs suchasinterleukin IL 1 IL 6 IL 8 ortumornecrosisfactor TNF havebeenconsideredinstrumentalintheoriginofthesereactions ThesemediatorscanaccumulateinhighconcentrationsinstoredPCs buttheirlevelsareverydependentontheWBCcontamination WBC reducedPCscontainfewifanyinflammatorycytokines andprestoragefiltrationofPCscancircumventtheaccumulationofthesemediatorsduringstorage ThereisalsoaremarkabledifferenceinthereportedincidenceofNHTRs accordingtothekindofPCtransfused TransfusionreactionsstilloccurafterthetransfusionofWBC reducedPCs Thus underlyingpathomechanismsbesidesthepresenceofWBC derivedinflammatorycytokinesmightalsobeinvolvedinNHTRs ABBREVIATIONS BC buffycoat IL interleukin MIP 1 macrophageinflammatoryprotein1 NHTR s nonhemolytictransfusionreaction s PC s plateletconcentrate s SD single donor TNF tumornecrosisfactor WBC s whitecell s TRANSFUSIONVolume39 November December1999 Febrileandallergictransfusionreactionsafterthetransfusionofwhitecell poorplateletpreparations Continuous FromtheInstituteofImmunologyandTransfusionMedicine UniversityofLubeck Germany andtheproDERMInstituteforAppliedDermatologicalResearch Hamburg Germany Addressreprintrequeststo HaraldKluter MD InstituteofTransfusionMedicineandClinicalImmunology GermanRedCrossBloodTransfusionServiceofBaden Wurttemberg Friedrich Ebert Strasse167 D 68167Mannheim Germany e mail h klueter blutspende de ReceivedforpublicationJanuary11 1999 revisionreceivedApril6 1999 andacceptedApril30 1999 TRANSFUSION1999 39 1179 1184 TRANSFUSIONVolume39 November December1999 Removalofsolublebiologicresponsemodifiers complementandchemolines byabedsidewhitecell reductionfilterE L SNYDER S MECHANIC L BARIL ANDR DAVENPORT CONCLUSION Thethird generationbedsidefilterusedinthisstudyreliablyreducedthelevelofwhitecellcontaminationto4log10whitecellsperPC Italsoloweredthelevelsofinterleukin8 RANTES andC3a Thefilterdidnot however remove scavenge theproinflammatorycytokinesinterleukin1 and6 ThemechanismofchemokineandC3aremovalbythefilterisunknown butitmayberelatedtoionicinteractionsbetweenthesebiologicresponsemodifiersandthefiltermedium TRANSFUSION1996 36 707 713 C3aAccumulatesinStoredPlateletProducts C3aandC3adesArg77InhibitNKCells EffectofPallPL100TMLeukodepletionFiltersonC3aRemovalFromPlateletConcentrates EffectofStorageonC3ainPooledRandomDonorPlateletsandFiltrationwithPXL8TM NotallFiltersaretheSame P8 13Twocasesofadversereactionduetoleukocyte reductionfilterAKokubunji 1 SKai1 RImaizumi1 JIkemoto1 MMisawa2 MNatsuaki3andHHara1 2Departmentsof1TransfusionMedicine 2InternalMedicine DivisionofHematologyandOncology 3Dermatology HyogoCollegeofMedicine Hyogo Japan Aims Mostadversereactionsassociatedwithtransfusionarenonhemolytictransfusionreactions NHTR withallergicsymptomssuchasrash itchingandurticaria Thecausesofthereactionaredifficulttobedeterminedinmostcases WeexaminedthecauseofNHTRinassociationwithleukocyte reductionfilters L Rfilters thatarewidelyusedtopreventalloimmunization Materialsandmethods NHTRoccurredintwopatients a13 year oldfemalewithaplasticanemia case1 anda69 year oldmalewithmyelodysplasticsyndrome case2 ToinvestigatethecauseofNHTRinthem severalantibodiessuchasanti platelet plasmaanti IgA C4andC9antibodies andIgAdeficientwerechecked WetriedtouseL Rfiltersfromdifferentmanufacturersandtransfusetheproductsofwashedredbloodcellsandwashedplatelets Results Incase1 sheshowedrash cough anddyspneaimmediatelyaftertransfusionofRC MAPwithL RfilterfromTcompanyathersixthtransfusion Incase2 athisthirdtransfusion hecomplainedofnausea chillnessafterstartingtransfusion WashingofthebloodproductswasnoteffectiveforpreventionofNHTRforthem Anti platelet anti IgA anti C4 andanti C9werenotdetected NoneofthepatientshadIgAdeficiency Atpresent wecouldtran