輸血過濾器的臨床應用.ppt

輸血過濾器的臨床應用陳育新 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 造成血小板減少的病人出血之原因 除了血小板數(shù)目外 很多其它的臨床癥狀也要考慮 例如敗血癥 尿毒癥 凝血功能異常 以及藥物的影響等 不之疾病造成血小板之減少癥 對輸血小板之反應不盡相同 如敗血癥 脾腫大 免疫性血小板減少癥 則對輸血小板之反應不佳 因此 除了血小板的數(shù)目外 引起血小板減少之原因及疾病亦應注意 才能掌握血小板輸注的正確時效 治療性血小板輸注呢 一般而言 是只對正在出血的血小板減少之病人之治療方法 這時在輸血小板之前及之后 對血中血小板數(shù)量的監(jiān)測與比較是很重要的 因為這樣可以評估血小板的存活數(shù)量 以及預測未來對輸血小板的需求 如果血小板的數(shù)量沒有爬升 即使是反覆的輸血 可能對病人并沒有什么好處 通常此時醫(yī)師必須積極去追查造成頑固性血小板減少的原因 有一些疾病所導致的血小板減少癥對輸血小板的反應良好 特別是針對骨髓抑制所造成的頑固性血小版減少癥 如化學治療后 放射線治療后 維持生活素缺乏 或是再生性不良性貧血等 另外有一些疾病所導致的血小板減少癥則對輸血小板反應不好 如 敗血癥 sepsis 脾臟腫大 splenectomy 以及免疫性血小板減少癥 包括自體免疫性血小板減少癥 immunethrombocytopenia 藥物引起之血小板減少癥 或是淋巴增生性疾病等 相對的 有一些疾病所導致的血小板減少癥 輸血小板則為其禁忌癥 如血栓性血小板減少性紫斑癥 thromboticthrombocytopenicpurpura 可能會因輸血小板而導致血栓更加惡化 頑固性 refractory 的血小板減少癥 頑固性 refractory 的血小板減少癥包含了 1 非免疫性 non immune 的頑固性的血小板減少癥2 異體免疫性 alloimmunization 的頑固性的血小板減少癥非免疫性的頑固性血小板減少癥的原因包含 敗血癥 sepsis 彌漫性血管內凝血癥 DIC 以及脾臟腫大 splenomegaly 等 對于非免疫性的頑固性的血小板減少癥的處理方法有 1 使用ABO血型相符之血品2 使用新鮮血小板3 在脾臟腫大 splenectomy 的病人則應增加血小板的劑量4 治療敗血癥 sepsis 及彌漫性血管內凝血癥 DIC 的原因5 考慮使用單一捐贈者HLA相符之血小板等 異體免疫性的頑固性血小板減少癥根據(jù)統(tǒng)計 約有20 至70 反覆輸血小板患者會產生異體抗體 allo antibody 一般發(fā)生在輸血小板兩個月內 有少數(shù)的病人于輸血小板前即有異體抗體 allo antibody 多半是因為從前曾輸血小板或懷孕的緣故 90 的異體抗體 allo antibody 與HLA typing有關 血小板只有攜帶第一型 classI HLA抗原 血小板本身并不足以對這些抗原引發(fā)原發(fā)性免疫性免疫反應 但是白血球同時攜帶第一型 classI 及第二型 classII HLA抗原 足以引發(fā)異體免疫 alloimmunization 反應 一但白血球引發(fā)原發(fā)性異體免疫反應 primaryalloimmunization 血小板亦引發(fā)次發(fā)性異體免疫反應 secondaryalloimmunization 使用類固醇 steroid 或脾藏切除 splenectomy 對處理具異體免疫抗體患者的效果不好 而使用IVIG亦只有對少數(shù)患者有效 減少捐贈者的人數(shù)并沒有減少異體免疫抗體產生的機會 即便是僅使用單一捐贈者輸血小板 亦只有少數(shù)研究報告顯示有統(tǒng)計上的差異 脾切除 脾切除對自體免疫性血小板減少癥及脾功能過盛之病人亦為一很好之治療方法 根據(jù)我們最進之統(tǒng)計資料約有70 脾切除后之自體免疫性血小板減少之病人 不必服藥而其小血小板有明顯之升高至正常護接近正常之現(xiàn)象 臨床上紅血球抗體的發(fā)生 與紅血球抗原的致免疫性 immunogenecity 或稱抗原性 有關 當然 致免疫性之高低 雖然主要是因抗原不同而異 但免疫途徑 免疫方法及頻率也有所影響 宿主本身的免疫力和身體狀況更是影響抗體發(fā)生的重大因素 紅血球抗原的致免疫性以Rh D 抗原最強 K抗原其次 其大致的致免疫性如下 以一次輸血后會發(fā)生抗體的頻率表示 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發(fā)生的概率并無法因Prestorage之白血球過濾處理而具有任何統(tǒng)計上意義之降低 目前一系列新的證據(jù)顯示 使用乏白血球處理后之血小板 能使NH F TR發(fā)生比率再降低之關鍵并非以Prestorage方式去白血球可以降低之Cytokine 而在血小板本身產生之ChemokineRANTES系列 說明請參考后附之 Transfusion1999 39 1179 1184 期刊所發(fā)表之論文 在該篇論文中詳細記錄 統(tǒng)計 分析了1992 1996年間 德國血液及腫瘤科因化療或脊髓功能不健全而造成血小板缺乏癥而需輸血小板患者之所有輸血反應之記錄 其二組對照比較之情況 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