HIV相关的贫血课件

Anemiainhuman

immunodeficiencyvirus(HIV)–infectedpatientsHIV相关的贫血贫血定义：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).HIV相关的贫血分类：★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HIV相关的贫血一、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HIV相关的贫血※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HIV相关的贫血Background---2000Despiteimportantadvancesinantiretroviraltherapy,anemiaremainsaprobleminmanyHIV-infectedpatientsAnemiahasadeleteriouseffectonbothfunctionalcapacityandqualityoflife,andhasbeenassociatedwithshortenedsurvival.HIV相关的贫血InFebruaryandJuneof1998,TheAnemiainHIVWorkingGroup,anexpertpanelofAIDScliniciansfromtheUnitedStates,convenedtodiscussthat：theimpactofanemiainpatientswithHIVinfectiontheavailabletreatmentoptionsthepracticestrategiesandfutureresearchdirectionsHIV相关的贫血AnemiaisacommoncomplicationofHIVinfection﹡HIV-infectedpatientstreatedfromJanuary1990throughAugust1996,thel-yearincidenceofanemia(definedasahemoglobinlevel<10g/dL)was3.2%inthe6094cohortmemberswithHIVbutnotAIDS,12.1%inthe2579memberswithimmunologicAIDS(CD4+cellcount<200/mm3),and36.9%inthe4624memberswithclinicalAIDS.﹡78%wereregardedasnotdrugrelatedHIV相关的贫血AnemiainHIVInfection:ClinicalImpact

andEvidence-BasedManagementStrategiesIn2002,16membersoftheAnemiainHIVWorkingGroup,anexpertpanelofphysiciansinvolvedinthecareofHIV-infectedpatientsthatmetfirstin1998,reconvenedtoassessnewdataandtotranslatethesedataintoevidence-basedtreatmentguidelinesHIV相关的贫血theprevalenceofanemiainthehighlyactiveantiretroviraltherapyeratheriskfactorsthatareindependentlyassociatedwiththedevelopmentofanemiatheimpactofanemiaonqualityoflife,physicalfunctioning,andsurvivalevidence-basedguidelinesfortreatmentofanemiainHIV-infectedpatientsAnemiaassociationwithdiseaseprogressionanddecreasedsurvivalHIV相关的贫血WHATCAUSESANEMIAINHIVINFECTEDPERSONSBloodloss---neoplasticdisease,gastrointestinallesionsOtherpathophysiologyofHIV-associatedanemia☆decreasedRBCproduction☆increasedRBCdestruction☆ineffectiveRBCproductionHIV相关的贫血DecreasedRBCproductionneoplasm,infection,myelosuppressivemedications,HIVinfectionitself,adecreasedproductionofendogenouserythropoietin,abluntedresponsetoerythropoietin,hypogonadismHIV相关的贫血抗逆转录病毒药物-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-aHIV相关的贫血IncreasedRBCdestructionRBCdestructioninthespleenorthecirculatorsystem☆RBCautoantibodies,hemophagocyticsyndrome,disseminatedintravascularcoagulation,thromboticthrombocytopenicpurpura,orglucose-6-phosphatedehydrogenasedeficiency---Hemolyticanemia☆variousmedicationsHIV相关的贫血IneffectiveRBCproductionNutritionaldeficiencies---iron,folicacid,orvitaminB12HIV相关的贫血WHATFACTORSAREASSOCIATEDWITH

ANEMIAINHIV-INFECTEDPERSONSzidovudineuse,CD4cellcountsof<200cells/mL,increasedvirusload,andanumberofadditionalfactorsHIV相关的贫血Sex---menstrualbloodlossandtothedrainsonironstoresthatoccurwithpregnancyanddeliveryRace---39%amongAfricanAmericanwomen,19%amongwhitewomen,31%amongAfricanAmericanmen,and12%amongwhitemen（presenceofinheritedhematologicdisorders,suchassicklecelldiseaseandthalessemia；Dietary）HIV相关的贫血Zidovudinetreatment---bonemarrowsuppression(hemoglobin<12g/dL)inthepre-HAARTera(1993–1996),useofzidovudineduringtheHAARTera(1996–2000)wasnotsignificantly(hemoglobin<10g/dL)in41.6%ofsubjectsreceivingzidovudinetherapy,comparedwith34.3%ofthosenotreceivingzidovudine(P<.01)HIV相关的贫血WorseningHIVdiseaseparametersLowCD4cellcounts(<200cells/mL)andhigherHIV-1RNAlevelsinplasmahaveeachbeenindependentlyassociatedwithanincreasedriskofanemiaHIV相关的贫血WHATISTHESIGNIFICANCEOFANEMIA

INHIV-INFECTEDPERSONSassociationbetweenanemiaatbaseline,decreasedsurvival,andincreaseddiseaseprogressionHIV相关的贫血THEIMPACTOFANEMIAINHIVINFECTED

PERSONSImpactoffatigueImpactofcorrectionofanemia---

Smallincreasesinthehemoglobinlevel(upto2g/dL)wereassociatedwithabeneficialeffectontotalqualityoflifeHIV相关的贫血THEEFFECTOFHAART

ONTHEPREVALENCEOFANEMIAAlthoughtheprevalenceofsevereanemiahasdecreasedsincetheintroductionofHAART,mild-to-moderateanemiacontinuestobecommonEvenwithuseofHAART,anemiaremainsstronglyandconsistentlyassociatedwithHIVdiseaseprogression---hemoglobinlevelsdecrease,theriskofdiseaseprogressionincreasesHIV相关的贫血THECURRENT

TREATMENTGUIDELINESFORANEMIAAddresscorrectablecausesofanemiaUseofHAART---

HAARTwassignificantlyassociatedwithcorrectionofanemia;improvementwasnotedwithin6months,andagreaterresolutionoccurredafteralongerdurationUseofepoetinalfaConsensusrecommendations:☆

MonitorhemoglobinlevelsroutinelyHIV相关的贫血☆Ifthehemoglobinlevelislowerthannormal---ruleoutorcorrecttreatablecauses☆InitiateHAARTifwarranted☆Ifcorrectablecausesofanemiahavebeenruledoutandthehemoglobinlevelis<13g/dLinmenand<12g/dLinwomen---epoetinalfatherapyatadosageof40,000Uonceperweek.☆Anticipatedbenefitsofepoetinalfatreatment☆Continueepoetinalfatherapyuntilsymptomshaveresolvedandhemoglobinlevelsof13g/dLformenor12g/dLforwomenHIV相关的贫血FUTURERESEARCHONANEMIAfurtheringunderstandingofthecausesofanemiavariousHAARTregimensontheprevalenceofanemiaoptimaldosingstrategiesfortheuseofepoetinalfaCost-benefitanalysesHIV相关的贫血BiologyofAnemia,DifferentialDiagnosis,andTreatmentOptionsTheBiologyofHIV-RelatedAnemiaThecausesaremultifactorial:---HIVmaydirectlyaffect:bonemarrowstromalcellorcausecytokinesecretionTumornecrosisfactorandothercytokinesinhibithematopoiesisparvovirusB19infectionHIV相关的贫血medications,opportunisticinfections,neoplasms,nutritionalabnormalitiesstemmingfromanorexia,malabsorption,metabolicdisordersthatotherconditions,suchashemolysisorgastrointestinalbleeding,mayalsooccurinthesepatientsHIV相关的贫血DifferentialDiagnosisbeingtreatedwithmultiplemedicationsmayhavemorethanoneco-morbidconditionrequiremultipleevaluationsHIV相关的贫血HIV相关的贫血HIV相关的贫血distinguishtheanemiaofchronicdiseasefromthatcausedbyirondeficiency：bothinalowserumironlevel,lowtotaliron-bindingcapacityandserumferritinlevels>100mg/L---unlikelytohaveirondeficiency;supplementwithironfor7–10days---re-evaluatetheanemiaHIV相关的贫血TreatmentOptions※Treatmentshouldbechosentoaddresstheunderlyingcauseofthisdisorder※Bloodtransfusion---severeanemia,withahemoglobinlevelof<8g/dL.※Epoetinalfa---4–8weeks,itsefficacyandsafetyforpatientswithmildsymptomaticormoderateHIV-relatedanemia※Androgens---increaseproductionoferythropoietinwithanemiacausedbybonemarrowfailureHIV相关的贫血HIV-AssociatedAutoimmuneHemolyticAnemiaThisreviewarticlediscussestheetiology,pathophysiology,clinicalfeatures,diagnosis,treatment,andcomplicationsofautoimmunehemolyticanemia(AIHA)associatedwithHIVinfection.HIV相关的贫血ETIOLOGYAIHAresultsfromthedestructionoferythrocytesbyantibodies.TheetiologiesforAIHAarevariousincludingidiopathiccauses,drugs,infectiousagents,neoplasms,orautoimmunediseaseHIV相关的贫血SeveralmechanismshavebeenpostulatedtoExplainwhyAIHAdevelopsinpatientswithAIDS◊presenceoferythrocyteautoantibodiesorthepresenceofhypergammaglobulinemiamayresultinnonspecificcoatingofoverabundantimmunoglobulinG(IgG)toautologouserythrocytes◊presenceofimmunecomplex-associatedIgG,maybindtoerythrocytesviaC3breceptorsHIV相关的贫血◊abnormalB-cellregulationbyHIV-infectedTcells◊InfectiousagentsassociatedwithAIDSmaybeassociatedwiththeproductionofautoantibodies◊lymphomaHIV相关的贫血CLINICALPRESENTATIONAnemia,pallor,mildjaundice,andsplenomegaly---30%AIHAcanbeclassifiedasmild,moderate,orsevere★Mildhemolyticanemiaischaracterizedbypositivedirectantiglobulintestresultsonly★Moderateanemiaischaracterizedbyanemiaandsplenomegaly★Severeanemiaischaracterizedbyfulminanthemolysiswithmarkedspherocytosis,hyperbilirubinemia,absentordecreasedlevelsofhaptoglobin,andhemoglobinuriaHIV相关的贫血DIAGNOSISPositiveCoombs’testSerologicfindings：Typesofantierythrocyteantibodies---includethecoatingoferythrocytesbybothIgGandC3,orIgGaloneConcomitantcoldandwarmantibodiesHIV相关的贫血TREATMENTmonitoredforpossibleprogressionofthehemolysisbloodtransfusion;corticosteroids,immunoglobulins,splenectomy,immunosuppressivetherapy,plasmapheresis,andzidovudine.HIV相关的贫血COMPLICATIONS

★Bloodtransfusioncomplications---hemoglobinuria,tachycardia,vomiting,backpain,fever,hypotension,shock,andrenalfailure★Hypercoagulation---thromb