HIV相關(guān)貧血的學(xué)習(xí)課件第1頁(yè)/共43頁(yè)貧血定義：血紅蛋白Hb：男性低于120g/l，成年女性低于110g/l，孕婦低于100g/l。AccordingtoTheAnemiaHIVWorkingGroup(hemoglobinlevelof<12g/dLinmenand<11g/dLinwomen)(Volberding2000).第1頁(yè)/共42頁(yè)第2頁(yè)/共43頁(yè)分類：★急性、慢性★紅細(xì)胞形態(tài)（大細(xì)胞性、正常細(xì)胞性、小細(xì)胞低色素性）★骨髓增生情況：增生性貧血（溶血性、缺鐵性、巨幼貧）

增生低下貧血（再生障礙性貧血）

★病因分類第2頁(yè)/共42頁(yè)第3頁(yè)/共43頁(yè)一、紅細(xì)胞生成減少（一）造血干祖細(xì)胞異常※再生障礙性貧血※純紅再障

先天性：Diamond-Blackfan綜合征

后天性：

原發(fā)---部分患者血清中有自身EPO或幼紅細(xì)胞的抗體

繼發(fā)---藥物相關(guān)型、感染相關(guān)型、

自身免疫病相關(guān)型、淋巴細(xì)胞增殖

性疾病相關(guān)型第3頁(yè)/共42頁(yè)第4頁(yè)/共43頁(yè)※先天性細(xì)胞生成異常性貧血※造血系統(tǒng)惡性克隆性疾病（二）造血微環(huán)境異常※骨髓基質(zhì)、基質(zhì)細(xì)胞受損※造血調(diào)節(jié)因子水平異常：SCF、IL、GM-CSF、G-CSF、EPO、TPO、TGF、TNF、IFN※造血原料不足或利用障礙二、溶血性貧血三、失血性貧血第4頁(yè)/共42頁(yè)第5頁(yè)/共43頁(yè)Background---2000Despiteimportantadvancesinantiretroviraltherapy,anemiaremainsaprobleminmanyHIV-infectedpatientsAnemiahasadeleteriouseffectonbothfunctionalcapacityandqualityoflife,andhasbeenassociatedwithshortenedsurvival.第5頁(yè)/共42頁(yè)第6頁(yè)/共43頁(yè)InFebruaryandJuneof1998,TheAnemiainHIVWorkingGroup,anexpertpanelofAIDScliniciansfromtheUnitedStates,convenedtodiscussthat：theimpactofanemiainpatientswithHIVinfectiontheavailabletreatmentoptionsthepracticestrategiesandfutureresearchdirections第6頁(yè)/共42頁(yè)第7頁(yè)/共43頁(yè)AnemiaisacommoncomplicationofHIVinfection﹡HIV-infectedpatientstreatedfromJanuary1990throughAugust1996,thel-yearincidenceofanemia(definedasahemoglobinlevel<10g/dL)was3.2%inthe6094cohortmemberswithHIVbutnotAIDS,12.1%inthe2579memberswithimmunologicAIDS(CD4+cellcount<200/mm3),and36.9%inthe4624memberswithclinicalAIDS.﹡78%wereregardedasnotdrugrelated第7頁(yè)/共42頁(yè)第8頁(yè)/共43頁(yè)AnemiainHIVInfection:ClinicalImpact

andEvidence-BasedManagementStrategiesIn2002,16membersoftheAnemiainHIVWorkingGroup,anexpertpanelofphysiciansinvolvedinthecareofHIV-infectedpatientsthatmetfirstin1998,reconvenedtoassessnewdataandtotranslatethesedataintoevidence-basedtreatmentguidelines第8頁(yè)/共42頁(yè)第9頁(yè)/共43頁(yè)theprevalenceofanemiainthehighlyactiveantiretroviraltherapyeratheriskfactorsthatareindependentlyassociatedwiththedevelopmentofanemiatheimpactofanemiaonqualityoflife,physicalfunctioning,andsurvivalevidence-basedguidelinesfortreatmentofanemiainHIV-infectedpatientsAnemiaassociationwithdiseaseprogressionanddecreasedsurvival第9頁(yè)/共42頁(yè)第10頁(yè)/共43頁(yè)WHATCAUSESANEMIAINHIVINFECTEDPERSONSBloodloss---neoplasticdisease,gastrointestinallesionsOtherpathophysiologyofHIV-associatedanemia☆decreasedRBCproduction☆increasedRBCdestruction☆ineffectiveRBCproduction第10頁(yè)/共42頁(yè)第11頁(yè)/共43頁(yè)DecreasedRBCproductionneoplasm,infection,myelosuppressivemedications,HIVinfectionitself,adecreasedproductionofendogenouserythropoietin,abluntedresponsetoerythropoietin,hypogonadism第11頁(yè)/共42頁(yè)第12頁(yè)/共43頁(yè)抗逆轉(zhuǎn)錄病毒藥物-扎西他濱-齊多夫定抗病毒藥-更昔洛韋-膦甲酸鈉-西多福韋抗真菌藥物-氟胞嘧啶-兩性霉素抗肺孢子菌藥物-磺胺類藥物

-甲氧芐啶

-乙胺嘧啶

-噴他脒抗腫瘤藥物-環(huán)磷酰胺

-阿霉素

-甲氨蝶呤

-紫杉醇

-長(zhǎng)春堿

-脂質(zhì)體阿霉素

-脂質(zhì)體柔紅霉素免疫反應(yīng)調(diào)節(jié)劑-干擾素-a第12頁(yè)/共42頁(yè)第13頁(yè)/共43頁(yè)IncreasedRBCdestructionRBCdestructioninthespleenorthecirculatorsystem☆RBCautoantibodies,hemophagocyticsyndrome,disseminatedintravascularcoagulation,thromboticthrombocytopenicpurpura,orglucose-6-phosphatedehydrogenasedeficiency---Hemolyticanemia☆variousmedications第13頁(yè)/共42頁(yè)第14頁(yè)/共43頁(yè)IneffectiveRBCproductionNutritionaldeficiencies---iron,folicacid,orvitaminB12第14頁(yè)/共42頁(yè)第15頁(yè)/共43頁(yè)WHATFACTORSAREASSOCIATEDWITH

ANEMIAINHIV-INFECTEDPERSONSzidovudineuse,CD4cellcountsof<200cells/mL,increasedvirusload,andanumberofadditionalfactors第15頁(yè)/共42頁(yè)第16頁(yè)/共43頁(yè)Sex---menstrualbloodlossandtothedrainsonironstoresthatoccurwithpregnancyanddeliveryRace---39%amongAfricanAmericanwomen,19%amongwhitewomen,31%amongAfricanAmericanmen,and12%amongwhitemen（presenceofinheritedhematologicdisorders,suchassicklecelldiseaseandthalessemia；Dietary）第16頁(yè)/共42頁(yè)第17頁(yè)/共43頁(yè)Zidovudinetreatment---bonemarrowsuppression(hemoglobin<12g/dL)inthepre-HAARTera(1993–1996),useofzidovudineduringtheHAARTera(1996–2000)wasnotsignificantly(hemoglobin<10g/dL)in41.6%ofsubjectsreceivingzidovudinetherapy,comparedwith34.3%ofthosenotreceivingzidovudine(P<.01)第17頁(yè)/共42頁(yè)第18頁(yè)/共43頁(yè)WorseningHIVdiseaseparametersLowCD4cellcounts(<200cells/mL)andhigherHIV-1RNAlevelsinplasmahaveeachbeenindependentlyassociatedwithanincreasedriskofanemia第18頁(yè)/共42頁(yè)第19頁(yè)/共43頁(yè)WHATISTHESIGNIFICANCEOFANEMIA

INHIV-INFECTEDPERSONSassociationbetweenanemiaatbaseline,decreasedsurvival,andincreaseddiseaseprogression第19頁(yè)/共42頁(yè)第20頁(yè)/共43頁(yè)THEIMPACTOFANEMIAINHIVINFECTED

PERSONSImpactoffatigueImpactofcorrectionofanemia---

Smallincreasesinthehemoglobinlevel(upto2g/dL)wereassociatedwithabeneficialeffectontotalqualityoflife第20頁(yè)/共42頁(yè)第21頁(yè)/共43頁(yè)THEEFFECTOFHAART

ONTHEPREVALENCEOFANEMIAAlthoughtheprevalenceofsevereanemiahasdecreasedsincetheintroductionofHAART,mild-to-moderateanemiacontinuestobecommonEvenwithuseofHAART,anemiaremainsstronglyandconsistentlyassociatedwithHIVdiseaseprogression---hemoglobinlevelsdecrease,theriskofdiseaseprogressionincreases第21頁(yè)/共42頁(yè)第22頁(yè)/共43頁(yè)THECURRENT

TREATMENTGUIDELINESFORANEMIAAddresscorrectablecausesofanemiaUseofHAART---

HAARTwassignificantlyassociatedwithcorrectionofanemia;improvementwasnotedwithin6months,andagreaterresolutionoccurredafteralongerdurationUseofepoetinalfaConsensusrecommendations:☆

Monitorhemoglobinlevelsroutinely第22頁(yè)/共42頁(yè)第23頁(yè)/共43頁(yè)☆I(lǐng)fthehemoglobinlevelislowerthannormal---ruleoutorcorrecttreatablecauses☆I(lǐng)nitiateHAARTifwarranted☆I(lǐng)fcorrectablecausesofanemiahavebeenruledoutandthehemoglobinlevelis<13g/dLinmenand<12g/dLinwomen---epoetinalfatherapyatadosageof40,000Uonceperweek.☆A(yù)nticipatedbenefitsofepoetinalfatreatment☆Continueepoetinalfatherapyuntilsymptomshaveresolvedandhemoglobinlevelsof13g/dLformenor12g/dLforwomen第23頁(yè)/共42頁(yè)第24頁(yè)/共43頁(yè)FUTURERESEARCHONANEMIAfurtheringunderstandingofthecausesofanemiavariousHAARTregimensontheprevalenceofanemiaoptimaldosingstrategiesfortheuseofepoetinalfaCost-benefitanalyses第24頁(yè)/共42頁(yè)第25頁(yè)/共43頁(yè)BiologyofAnemia,DifferentialDiagnosis,andTreatmentOptionsTheBiologyofHIV-RelatedAnemiaThecausesaremultifactorial:---HIVmaydirectlyaffect:bonemarrowstromalcellorcausecytokinesecretionTumornecrosisfactorandothercytokinesinhibithematopoiesisparvovirusB19infection第25頁(yè)/共42頁(yè)第26頁(yè)/共43頁(yè)medications,opportunisticinfections,neoplasms,nutritionalabnormalitiesstemmingfromanorexia,malabsorption,metabolicdisordersthatotherconditions,suchashemolysisorgastrointestinalbleeding,mayalsooccurinthesepatients第26頁(yè)/共42頁(yè)第27頁(yè)/共43頁(yè)DifferentialDiagnosisbeingtreatedwithmultiplemedicationsmayhavemorethanoneco-morbidconditionrequiremultipleevaluations第27頁(yè)/共42頁(yè)第28頁(yè)/共43頁(yè)第28頁(yè)/共42頁(yè)第29頁(yè)/共43頁(yè)第29頁(yè)/共42頁(yè)第30頁(yè)/共43頁(yè)distinguishtheanemiaofchronicdiseasefromthatcausedbyirondeficiency：bothinalowserumironlevel,lowtotaliron-bindingcapacityandserumferritinlevels>100mg/L---unlikelytohaveirondeficiency;supplementwithironfor7–10days---re-evaluatetheanemia第30頁(yè)/共42頁(yè)第31頁(yè)/共43頁(yè)TreatmentOptions※Treatmentshouldbechosentoaddresstheunderlyingcauseofthisdisorder※Bloodtransfusion---severeanemia,withahemoglobinlevelof<8g/dL.※Epoetinalfa---4–8weeks,itsefficacyandsafetyforpatientswithmildsymptomaticormoderateHIV-relatedanemia※Androgens---increaseproductionoferythropoietinwithanemiacausedbybonemarrowfailure第31頁(yè)/共42頁(yè)第32頁(yè)/共43頁(yè)HIV-AssociatedAutoimmuneHemolyticAnemiaThisreviewarticlediscussestheetiology,pathophysiology,clinicalfeatures,diagnosis,treatment,andcomplicationsofautoimmunehemolyticanemia(AIHA)associatedwithHIVinfection.第32頁(yè)/共42頁(yè)第33頁(yè)/共43頁(yè)ETIOLOGYAIHAresultsfromthedestructionoferythrocytesbyantibodies.TheetiologiesforAIHAarevariousincludingidiopathiccauses,drugs,infectiousagents,neoplasms,orautoimmunedisease第33頁(yè)/共42頁(yè)第34頁(yè)/共43頁(yè)SeveralmechanismshavebeenpostulatedtoExplainwhyAIHAdevelopsinpatientswithAIDS?presenceoferythrocyteautoantibodiesorthepresenceofhypergammaglobulinemiamayresultinnonspecificcoatingofoverabundantimmunoglobulinG(IgG)toautologouserythrocytes?presenceofimmunecomplex-associatedIgG,maybindtoerythrocytesviaC3breceptors第34頁(yè)/共42頁(yè)第35頁(yè)/共43頁(yè)?abnormalB-cellregulationbyHIV-infectedTcells?InfectiousagentsassociatedwithAIDSmaybeassociatedwiththeproductionofautoantibodies?lymphoma第35頁(yè)/共42頁(yè)第36頁(yè)/共43頁(yè)CLINICALPRESENTATIONAnemia,pallor,mildjaundice,andsplenomegaly---30%AIHAcanbeclassifiedasmild,moderate,orsevere★Mildhemolyticanemiaischaracterizedbypositivedirectantiglobulintestresultsonly★Moderateanemiaischaracterizedbyanemiaandsplenomegaly★Severeanemiaischaracterizedbyfulminanthemolysiswithmarkedspherocytosis,hyperbilirubinemia,absentordecreasedlevelsofhaptoglobin,andhemoglobinuria第36頁(yè)/共42頁(yè)第37頁(yè)/共43頁(yè)DIAGNOSISPositiveCoombs’testSerologicfindings：Typesofantierythrocyteantibodies---includethecoatingoferythrocytesbybothIgGandC3,orIgGaloneConcomitantcoldandwarmantibodies第37頁(yè)/共42頁(yè)第38頁(yè)/共43頁(yè)TREATMENTmonitoredforpossibleprogressionofthehemolysisbloodtransfusion;corticosteroids,immunoglobulins,splenectomy,immunosuppressivetherapy,plasmapheresis,andzidovudine.第38頁(yè)/共42頁(yè)第39頁(yè)/共43頁(yè)COMPLICAT