输血过滤器的临床应用（课件）.ppt

1、 输血过滤器的临床应用 陈育新 Military AircraftMilitary Aircraft Engine Engine Intake AirIntake AirRoyal Navy Sea King Helicopter filtered by PALL Filtration1-2-301-2-30Leo YangLeo YangPall TWN SciencesPall TWN SciencesWelcome to Pall CorporationPall is All Around YouEnsuring the purity and clarity of the wine,En

2、suring the purity and clarity of the wine,beer and water you drinkbeer and water you drinkPall is All Around YouHelping to make vaccines pure and safeHelping to make vaccines pure and safeA Culture of Innovation1946Dr Pall invents porous stainless steel and founds the company that will become Pall C

3、orporation.1958Palls Filters provide protection for hydraulic systems on Jupiter C booster.1959Rigimesh filter media is developed by Pall for the protection of Boeing 707 hydraulic systems.1969Pall develops a spacesuit heat exchanger and lunar module filtration for the Apollo 11 mission.1971Blood fi

4、lters based on the Pall Ultipor filter media are introduced to protect cardiac patients from microemboli,improving post operative outcomes.A Culture of Innovation1979PMM filter media is developed as a clean-up solution for Three Mile Island site.1988Pall introduces its leukoreduction filters to comb

5、at post-transfusion fever and allergic reactions.1989Palls Scientific and Laboratory Services develops filtration and maintenance standards for hydraulics systems on the Eurotunnel boring machines,ensuring reliable operation under challenging environmental conditions.1990Dr.Pall is awarded the Natio

6、nal Medal of Technology by President George Bush Sr.A Culture of Innovation1991The Pall CentriSep System provides innovative protection for the militarys intake systems in harsh conditions during operation“Desert Storm”.1993The BB25 breathing circuit filter,developed by Pall to prevent contamination

7、 of ventilating equipment.It becomes critically important in fighting the spread of SARS and Avian Flu.1995Pall Corporation introduces the DV50,the first validated virus-retention cartridge filter for the pharmaceutical industry.2006Palls Acrodose PL System is introduced to increase the safety and a

8、vailability of life-saving platelets.Tomorrow Pall products will continue to protect mission critical systems in even the harshest environments.Filters Used for Blood Components AdministrationType of Filter Removal Type of Filter Removal CharacteristicCharacteristicClot Screen Pore Clot Screen Pore

9、size of 170 umsize of 170 umMicroaggregateMicroaggregate Pore Pore size of 20 40 umsize of 20 40 umLeukocyte removal Rate on Leukocyte removal Rate on the efficiency of the efficiency of leukocyte remove leukocyte remove -not by pore size-not by pore size BLOOD FILTRATION TECHNOLOGYBLOOD FILTRATION

10、TECHNOLOGYMicroaggregateMicroaggregateLeucocyteLeucocyte reduction reductionred cellsred cellsplateletsplateletssalvaged bloodsalvaged bloodBlood bank filtersBlood bank filtersBedside(hospital)filtersBedside(hospital)filtersTransfusion-AssociatedLeukocyte-Mediated MorbidityWalker JH.Walker JH.AmerAm

11、er J J ClinClin Path 88:374-8,1987 Path 88:374-8,1987TRANSFUSIONSNearly 1 in 5 transfusionsare associated with an adverse reactionCMV seroconversion7%Alloimmunization10%NHFTR0.5%Remaining1.7%Frequency of OccurrenceDose-Response for Transfusion and InfectionDose-Response for Transfusion and Infection

12、Patients transfused with 1 to 4 units have infectious complications rates approaching 20%.Dose-Response Relationship Dose-Response Relationship AllogeneicAllogeneic Transfusion and InfectionTransfusion and InfectionA single transfused unit has been correlated with significantly increased infectious

13、complications approximating 15%.CLINICAL EFFECTS OF CLINICAL EFFECTS OF CONTAMINATING LEUCOCYTESCONTAMINATING LEUCOCYTESHLA HLA AlloimmunisationAlloimmunisationReactionsReactions PlateletPlateletGraftGraftRefractorinessRefractoriness RejectionRejection Viral Transmission Viral Transmission Cytomegal

14、ovirus(CMV)Cytomegalovirus(CMV)EBV,HTLV I&II,EBV,HTLV I&II,VaricellaVaricella zoster zosterImmune SuppressionImmune SuppressionPost Post Cancer Cancer LatentLatentOperativeOperative RecurrenceRecurrenceViralViralInfectionInfectionReactivationReactivationContaminating Contaminating LeucocytesLeucocyt

15、esBenefits of ULR to Patients and Hospitals Established Suspected Plausible but not well-studied Reduce alloimmunization and associated platelet refractorinessi,ii,iii Mortgaging the future of transfusion recipients who may go on to become candidates for transplants Attenuated CMV infection and dise

16、aseiv,v,vi High risk patients(e.g.,neonates)may receive seronegative products with false negative rates as high as 1.3%vii or even 4.5%viii Abrogate FNHTRix,x,xi,xii,xiii Seldom is a history of FNHTR available nor can such reactions be predicted and there are costs associated with pt managementxiv R

17、educe morbidityxv,xvi,xvii,xviii(length of stay,infections,fever,MOF)and mortalityxix,xx among cardiac surgery patients Colorectal surgery pts show reduced infectious complication ratesxxi,xxii and lower hospital chargesxxiii,xxiv with leukofiltered blood Although clinical manifestation of transfusi

18、on-related immunomodulation remains controversialxxv,there are explanations for discrepant findings centered about study failures to control for confounding variablesxxvi such as age of blood products.TRALI may be due,in part,to lipids derived from white cells and pre-storage leukoreduction may redu

19、ce the transfusion burdenxxvii Like CMV,other cell-associated viruses are removed by leukofiltration,such as HTLV-1xxviii Leukoreduction filters have been shown to remove bacteria including Yersinia sp.xxix,coag-negative Staphylococcusxxx as well as parasites like Trypanosomesxxxi,to some extent and

20、 perhaps Leishmaniaxxxii.Intangible Benefits Associated with ULR Endorsed by both BPACxxxiii advising the FDA and BSACxxxiv advising DHHS,15 countries have adopted ULRxxxv as well as being 80%implemented in the USxxxvi with growing implications regarding issues of standard of care Managing dual inve

21、ntories is labor intensive and presents the risk of patients receiving non-LR blood when they need it Costs of implementing ULR have been justified by some major institutions such as Yale University Hospital 1-34-6789-131415-1819-2021,2223,24252627282930313233343536Known effects of LeucocytesAlloimm

22、unization -leading on to RefractorinessInfection transmission-viruses and bacteriaImmuno-modulation-higher incidence of post op.InfectionImmuno-suppression-higher AND increased incidence of solid tumour reformationALLOIMMUNISATIONANDREFRACTORINESS Antigen Presenting CellB-LymphocytePlasma CellMemory

23、 CellT-Lymphocyte DonorDonorRecipientRecipientTransfusionTransfusionY Y Y YY Y YY Y Y Y Y Y Y Y Y Y Y Y Y Antibody ProductionAntibody Production*The production of HLA antibodies is a 2 signal The production of HLA antibodies is a 2 signal process requiring the presence of both Class I process requir

24、ing the presence of both Class I and Class II antigensand Class II antigensLocation of HLA Location of HLA*HLA Class I HLA Class IPresent on ALL nucleated cells(white cells)and plateletsPresent on ALL nucleated cells(white cells)and platelets*HLA Class II HLA Class II Present ONLY on Present ONLY on

25、 MonocytesMonocytes,Macrophages,B-Lymphocytes,Macrophages,B-Lymphocytes,activated T-Lymphocytes,activated T-Lymphocytes,dendriticdendritic cells cellsNB:red cells do not express HLANB:red cells do not express HLAALLOIMMUNISATION%ALLOIMMUNISATION%Control Groups Filter GroupsControl Groups Filter Grou

26、psNumber of Average Platelets Average Admissions Transfused Platelet Costs($)LillLill et al.,A.S.H.1997 et al.,A.S.H.1997IN-PATIENT PLATELET USE&COSTS:A COMPARISON BETWEEN REFRACTORYAND NON-REFRACTORY PATIENTSGordon et al.,ASH 19960102030405060708090PatientNumberPlateletUnitsTransfusedLength ofStayP

27、lateletCostsTotal CostsRefractoryNon-Refractory%N=245N=480309.642.627.611.7$23,510$3,126$59,426$15,897Author Patient Group Alloimmunisation Refractoriness Blood Product ReductionStandard Leucodepleted Standard Leucodepleted Red Cells Platelets HLA MatchedT.R.A.P.Study,1997AML45%17%13%3%0%0%-Killick

28、et al.,1997 Aplastic 50%12%-0%-AnaemicsNovotney et al.,1995 Aplastic-12%-5%-ThrombocytopenicsAdamzik et al.,1995Cancer27%0%27%0%-8.3%-AML-15.7%-Blumberg et al.,1995AML-0%43.2%-*Lymphoma-43.7%50.3%-*Williamson et al.,1994Cancer37.5%22.4%31%24%-AML63%31%-Oksanen et al.,1994AML38%17%21%3%14.8%26.5%-*Sa

29、arinen et al.,1993Leukaemics30%0%10%0%13.6%28.6%-Bedford-Russell et al.,1993 Neonates30.4%0%-Myllyla et al.,1993Renal67%19%-Leukaemics-52%0%-AML-18%2.9%-Al-Momen et al.,1992Leukaemics-21.5%-van Prooijen et al.,1991Leukaemics-7.8%-7.8%-82%van Marwijk Kooy et al.,Leukaemics42%7%46%11%-1991Overall Mean

30、s:-42.6%12.3%30.1%6%15.6%24.7%82%82%*Authors found additional cost savings in terms of length of hospital stay(23-41%reduction)and total charges(10-41%reduction)in the Authors found additional cost savings in terms of length of hospital stay(23-41%reduction)and total charges(10-41%reduction)in the l

31、eucocyteleucocyte depleted arm depleted arm 造成血小板减少的病人出血之原因，除了血小板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，小板减少症，则对输血小板之反应不佳。因此，除了血小

32、板的数目外，引起血小板减少之原因及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，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，来对输血小板的需求。如果

33、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。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。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另外

34、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：败血症反应不好，如：败血症(sepsis)(sepsis)，脾脏肿大，脾脏肿大(splenectomysplenectomy)，以及免疫性血小板减少症，包括自体，以及免疫性血小板减少症，包括自体免疫性血小板减少症免疫性血小板减少症(immunethrombocytopeniaimmunethrombocytopenia)，药，药物引起之血小板减少症，或是淋巴增生性疾病等。相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

35、少性紫斑症则为其禁忌症。如血栓性血小板减少性紫斑症(thromboticthrombocytopenicthromboticthrombocytopenic purpurapurpura，可能会因输，可能会因输血小板而导致血栓更加恶化。血小板而导致血栓更加恶化。顽固性顽固性(refractory)(refractory)的血小板减少症：的血小板减少症：顽固性顽固性(refractory)(refractory)的血小板减少症包含了：的血小板减少症包含了：1.1.非免疫性非免疫性(non-immune)(non-immune)的顽固性的血小板减少症的顽固性的血小板减少症 2.2.异体免疫性异体免

36、疫性(alloimmunizationalloimmunization)的顽固性的血小板的顽固性的血小板减少症减少症 非免疫性的顽固性血小板减少症的原因包含：败血非免疫性的顽固性血小板减少症的原因包含：败血症症(sepsis)(sepsis)，弥漫性血管内凝血症，弥漫性血管内凝血症(DIC)(DIC)，以及脾脏肿，以及脾脏肿大大(splenomegalysplenomegaly)等。等。对于非免疫性的顽固性的血小板减少症的处理方法有：对于非免疫性的顽固性的血小板减少症的处理方法有：1.1.使用使用ABOABO血型相符之血品血型相符之血品2.2.使用新鲜血小板使用新鲜血小板3.3.在脾脏肿大在脾

37、脏肿大(splenectomysplenectomy)的病人则应增加血小板的剂的病人则应增加血小板的剂量量4.4.治疗败血症治疗败血症(sepsis)(sepsis)及弥漫性血管内凝血症及弥漫性血管内凝血症(DIC)(DIC)的原的原因因5.5.考虑使用单一捐赠者考虑使用单一捐赠者HLAHLA相符之血小板等相符之血小板等 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(a

38、llo-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(class II)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(primary alloimmunization)，血小板亦引发次发性异体免疫反应(secondary alloimmunization)。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

39、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，与红血球抗原的致临床上红血球抗体的发生，与红血球抗原的致免疫性免疫性(immunogenecityimmunogenecity，或称抗原性，或称抗原性)有关。当有关。当然，致免疫性之高低，虽然主要是因抗原不同而然，致免疫性之高低，虽然主要是因抗原不

40、同而异，但免疫途径、免疫方法及频率也有所影响，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的重大因素。红血球抗原的致免疫性以Rh(DRh(D)抗抗原最强，原最强，K K抗原其次。其大致的致免疫性如下抗原其次。其大致的致免疫性如下(以以一次输血后会发生抗体的频率表示一次输血后会发生抗体的频率表示)Non-hemolytic febrile transfusion reactions.Non-hemolytic febrile transfusion reactions.Alloim

41、munizationAlloimmunizationPost-transfusion thrombocytopeniaPost-transfusion thrombocytopeniaCytomegalovirus transmissionCytomegalovirus transmissionTransfusion induced Transfusion induced immunosuppressionimmunosuppression (infection,cancer recurrence)(infection,cancer recurrence)Reduction of the ri

42、sk of Reduction of the risk of nvCJDnvCJD transmission transmissionLeukocyte Depletion of Homologous Blood ProductsLeukocyte Depletion of Homologous Blood Products(Red cells,platelets,plasma)(Red cells,platelets,plasma)Barrier Retention and Pore SizeSCREEN FILTRATIONSCREEN FILTRATIONScreens 20-40um(

43、40um most Screens 20-40um(40um most common)common)Absolute filters.Large Absolute filters.Large surface area if membrane is surface area if membrane is pleated Normally made of pleated Normally made of polyesterpolyesterDEPTH FILTRATIONDEPTH FILTRATIONVariable pore size removal Variable pore size re

44、moval efficiency of particles/airefficiency of particles/airdependant on density Low dependant on density Low surface area.Modified surface area.Modified polyesters-adsorb leukocytes.polyesters-adsorb leukocytes.WHEN TO FILTER:THE LOGISTICSWHEN TO FILTER:THE LOGISTICSFilterFilterDonation Hold Donati

45、on Hold Processing Storage Transfusion Processing Storage TransfusionWarm Warm BloodBloodVariableVariableTemperatureTemperatureControlledControlledTemperatureTemperature Non-Hemolytic Febrile TransfusionNon-Hemolytic Febrile Transfusion Reactions ReactionsBuffy coat removalImugardSpin-cool filter(SQ

46、)Sepacell-R-500Pall RC100010203040506070Residual leukocyte count(109)1.0 0.5 0.2-0.1 0.05Seronegative vsUnscreened Filtered Bowden RA et al.Transfusion(1995)35:719-722 Transfusion induced Transfusion induced immunosuppressionimmunosuppression (infection)(infection)Adapted from Jensen et al.Lancet 19

47、96;348:841-845.0510152025NoneLeukoreducedAllogeneicWound InfectionPneumoniaReoperationInfection Rate(%)Infection Rate(%)or Reoperationor ReoperationReduces Wound Infection,Pneumonia and ReoperationTransfusion RegimenTransfusion RegimenPatient Charges024681012141618Length of StayNoneLeukoreducedAllog

48、eneic141411118 85 5Days in HospitalDays in HospitalDollars(thousands)Dollars(thousands)Cost-Effectiveness of LeukoreductionTransfusion RegimenTransfusion RegimenAdapted from Jensen et al.Transfusion 1995;35:719-722.The Road to Universal Leukocyte ReductionAmerican Red Cross BPAC Public StatementsAme

49、rican Red Cross BPAC Public StatementsThe American Red Cross will present the following views at the Food and Drug Administration Blood Products Advisory Committee(BPAC)meeting today and Friday.The BPAC advises the FDA on a variety of issues that pertain to blood products,from recommending approval

50、of new products to recommending changes of regulations.I t i s s t r i c t l y a n a d v i s o r y c o m m i t t e e.This information may appear somewhat technical,however,it involves Red Corss policy onf improved testing for infectious agents to improve the safety of Americas blood supply.AABBs Ass