HIV相关贫血的学习课件

HIV相关贫血的学习课件第1页/共43页贫血定义：血红蛋白Hb：男性低于120g/l，成年女性低于110g/l，孕妇低于100g/l。AccordingtoTheAnemiaHIVWorkingGroup(hemoglobinlevelof<12g/dLinmenand<11g/dLinwomen)(Volberding2000).第1页/共42页第2页/共43页分类：★急性、慢性★红细胞形态（大细胞性、正常细胞性、小细胞低色素性）★骨髓增生情况：增生性贫血（溶血性、缺铁性、巨幼贫）

增生低下贫血（再生障碍性贫血）

★病因分类第2页/共42页第3页/共43页一、红细胞生成减少（一）造血干祖细胞异常※再生障碍性贫血※纯红再障

先天性：Diamond-Blackfan综合征

后天性：

原发---部分患者血清中有自身EPO或幼红细胞的抗体

继发---药物相关型、感染相关型、

自身免疫病相关型、淋巴细胞增殖

性疾病相关型第3页/共42页第4页/共43页※先天性细胞生成异常性贫血※造血系统恶性克隆性疾病（二）造血微环境异常※骨髓基质、基质细胞受损※造血调节因子水平异常：SCF、IL、GM-CSF、G-CSF、EPO、TPO、TGF、TNF、IFN※造血原料不足或利用障碍二、溶血性贫血三、失血性贫血第4页/共42页第5页/共43页Background---2000Despiteimportantadvancesinantiretroviraltherapy,anemiaremainsaprobleminmanyHIV-infectedpatientsAnemiahasadeleteriouseffectonbothfunctionalcapacityandqualityoflife,andhasbeenassociatedwithshortenedsurvival.第5页/共42页第6页/共43页InFebruaryandJuneof1998,TheAnemiainHIVWorkingGroup,anexpertpanelofAIDScliniciansfromtheUnitedStates,convenedtodiscussthat：theimpactofanemiainpatientswithHIVinfectiontheavailabletreatmentoptionsthepracticestrategiesandfutureresearchdirections第6页/共42页第7页/共43页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页/共42页第8页/共43页AnemiainHIVInfection:ClinicalImpact

andEvidence-BasedManagementStrategiesIn2002,16membersoftheAnemiainHIVWorkingGroup,anexpertpanelofphysiciansinvolvedinthecareofHIV-infectedpatientsthatmetfirstin1998,reconvenedtoassessnewdataandtotranslatethesedataintoevidence-basedtreatmentguidelines第8页/共42页第9页/共43页theprevalenceofanemiainthehighlyactiveantiretroviraltherapyeratheriskfactorsthatareindependentlyassociatedwiththedevelopmentofanemiatheimpactofanemiaonqualityoflife,physicalfunctioning,andsurvivalevidence-basedguidelinesfortreatmentofanemiainHIV-infectedpatientsAnemiaassociationwithdiseaseprogressionanddecreasedsurvival第9页/共42页第10页/共43页WHATCAUSESANEMIAINHIVINFECTEDPERSONSBloodloss---neoplasticdisease,gastrointestinallesionsOtherpathophysiologyofHIV-associatedanemia☆decreasedRBCproduction☆increasedRBCdestruction☆ineffectiveRBCproduction第10页/共42页第11页/共43页DecreasedRBCproductionneoplasm,infection,myelosuppressivemedications,HIVinfectionitself,adecreasedproductionofendogenouserythropoietin,abluntedresponsetoerythropoietin,hypogonadism第11页/共42页第12页/共43页抗逆转录病毒药物-扎西他滨-齐多夫定抗病毒药-更昔洛韦-膦甲酸钠-西多福韦抗真菌药物-氟胞嘧啶-两性霉素抗肺孢子菌药物-磺胺类药物

-甲氧苄啶

-乙胺嘧啶

-喷他脒抗肿瘤药物-环磷酰胺

-阿霉素

-甲氨蝶呤

-紫杉醇

-长春碱

-脂质体阿霉素

-脂质体柔红霉素免疫反应调节剂-干扰素-a第12页/共42页第13页/共43页IncreasedRBCdestructionRBCdestructioninthespleenorthecirculatorsystem☆RBCautoantibodies,hemophagocyticsyndrome,disseminatedintravascularcoagulation,thromboticthrombocytopenicpurpura,orglucose-6-phosphatedehydrogenasedeficiency---Hemolyticanemia☆variousmedications第13页/共42页第14页/共43页IneffectiveRBCproductionNutritionaldeficiencies---iron,folicacid,orvitaminB12第14页/共42页第15页/共43页WHATFACTORSAREASSOCIATEDWITH

ANEMIAINHIV-INFECTEDPERSONSzidovudineuse,CD4cellcountsof<200cells/mL,increasedvirusload,andanumberofadditionalfactors第15页/共42页第16页/共43页Sex---menstrualbloodlossandtothedrainsonironstoresthatoccurwithpregnancyanddeliveryRace---39%amongAfricanAmericanwomen,19%amongwhitewomen,31%amongAfricanAmericanmen,and12%amongwhitemen（presenceofinheritedhematologicdisorders,suchassicklecelldiseaseandthalessemia；Dietary）第16页/共42页第17页/共43页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页/共42页第18页/共43页WorseningHIVdiseaseparametersLowCD4cellcounts(<200cells/mL)andhigherHIV-1RNAlevelsinplasmahaveeachbeenindependentlyassociatedwithanincreasedriskofanemia第18页/共42页第19页/共43页WHATISTHESIGNIFICANCEOFANEMIA

INHIV-INFECTEDPERSONSassociationbetweenanemiaatbaseline,decreasedsurvival,andincreaseddiseaseprogression第19页/共42页第20页/共43页THEIMPACTOFANEMIAINHIVINFECTED

PERSONSImpactoffatigueImpactofcorrectionofanemia---

Smallincreasesinthehemoglobinlevel(upto2g/dL)wereassociatedwithabeneficialeffectontotalqualityoflife第20页/共42页第21页/共43页THEEFFECTOFHAART

ONTHEPREVALENCEOFANEMIAAlthoughtheprevalenceofsevereanemiahasdecreasedsincetheintroductionofHAART,mild-to-moderateanemiacontinuestobecommonEvenwithuseofHAART,anemiaremainsstronglyandconsistentlyassociatedwithHIVdiseaseprogression---hemoglobinlevelsdecrease,theriskofdiseaseprogressionincreases第21页/共42页第22页/共43页THECURRENT

TREATMENTGUIDELINESFORANEMIAAddresscorrectablecausesofanemiaUseofHAART---

HAARTwassignificantlyassociatedwithcorrectionofanemia;improvementwasnotedwithin6months,andagreaterresolutionoccurredafteralongerdurationUseofepoetinalfaConsensusrecommendations:☆

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