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HIV相關(guān)的貧血貧血定義: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).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※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?!撬杌|(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Background---2000Despiteimportantadvancesinantiretroviraltherapy,anemiaremainsaprobleminmanyHIV-infectedpatientsAnemiahasadeleteriouseffectonbothfunctionalcapacityandqualityoflife,andhasbeenassociatedwithshortenedsurvival.InFebruaryandJuneof1998,TheAnemiainHIVWorkingGroup,anexpertpanelofAIDScliniciansfromtheUnitedStates,convenedtodiscussthat:theimpactofanemiainpatientswithHIVinfectiontheavailabletreatmentoptionsthepracticestrategiesandfutureresearchdirectionsAnemiaisacommoncomplicationofHIVinfection﹡HIV-infectedpatientstreatedfromJanuary1990throughAugust1996,thel-yearincidenceofanemia(definedasahemoglobinlevel<10g/dL)was3.2%inthe6094cohortmemberswithHIVbutnotAIDS,12.1%inthe2579memberswithimmunologicAIDS(CD4+cellcount<200/mm3),and36.9%inthe4624memberswithclinicalAIDS.﹡78%wereregardedasnotdrugrelatedAnemiainHIVInfection:ClinicalImpact

andEvidence-BasedManagementStrategiesIn2002,16membersoftheAnemiainHIVWorkingGroup,anexpertpanelofphysiciansinvolvedinthecareofHIV-infectedpatientsthatmetfirstin1998,reconvenedtoassessnewdataandtotranslatethesedataintoevidence-basedtreatmentguidelinestheprevalenceofanemiainthehighlyactiveantiretroviraltherapyeratheriskfactorsthatareindependentlyassociatedwiththedevelopmentofanemiatheimpactofanemiaonqualityoflife,physicalfunctioning,andsurvivalevidence-basedguidelinesfortreatmentofanemiainHIV-infectedpatientsAnemiaassociationwithdiseaseprogressionanddecreasedsurvivalWHATCAUSESANEMIAINHIVINFECTEDPERSONSBloodloss---neoplasticdisease,gastrointestinallesionsOtherpathophysiologyofHIV-associatedanemia☆decreasedRBCproduction☆increasedRBCdestruction☆ineffectiveRBCproductionDecreasedRBCproductionneoplasm,infection,myelosuppressivemedications,HIVinfectionitself,adecreasedproductionofendogenouserythropoietin,abluntedresponsetoerythropoietin,hypogonadism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-aIncreasedRBCdestructionRBCdestructioninthespleenorthecirculatorsystem☆RBCautoantibodies,hemophagocyticsyndrome,disseminatedintravascularcoagulation,thromboticthrombocytopenicpurpura,orglucose-6-phosphatedehydrogenasedeficiency---Hemolyticanemia☆variousmedicationsIneffectiveRBCproductionNutritionaldeficiencies---iron,folicacid,orvitaminB12WHATFACTORSAREASSOCIATEDWITH

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

INHIV-INFECTEDPERSONSassociationbetweenanemiaatbaseline,decreasedsurvival,andincreaseddiseaseprogressionTHEIMPACTOFANEMIAINHIVINFECTED

PERSONSImpactoffatigueImpactofcorrectionofanemia---

Smallincreasesinthehemoglobinlevel(upto2g/dL)wereassociatedwithabeneficialeffectontotalqualityoflifeTHEEFFECTOFHAART

ONTHEPREVALENCEOFANEMIAAlthoughtheprevalenceofsevereanemiahasdecreasedsincetheintroductionofHAART,mild-to-moderateanemiacontinuestobecommonEvenwithuseofHAART,anemiaremainsstronglyandconsistentlyassociatedwithHIVdiseaseprogression---hemoglobinlevelsdecrease,theriskofdiseaseprogressionincreasesTHECURRENT

TREATMENTGUIDELINESFORANEMIAAddresscorrectablecausesofanemiaUseofHAART---

HAARTwassignificantlyassociatedwithcorrectionofanemia;improvementwasnotedwithin6months,andagreaterresolutionoccurredafteralongerdurationUseofepoetinalfaConsensusrecommendations:☆

Monitorhemoglobinlevelsroutinely☆I(lǐng)fthehemoglobinlevelislowerthannormal---ruleoutorcorrecttreatablecauses☆I(lǐng)nitiateHAARTifwarranted☆I(lǐng)fcorrectablecausesofanemiahavebeenruledoutandthehemoglobinlevelis<13g/dLinmenand<12g/dLinwomen---epoetinalfatherapyatadosageof40,000Uonceperweek.☆A(yù)nticipatedbenefitsofepoetinalfatreatment☆Continueepoetinalfatherapyuntilsymptomshaveresolvedandhemoglobinlevelsof13g/dLformenor12g/dLforwomenFUTURERESEARCHONANEMIAfurtheringunderstandingofthecausesofanemiavariousHAARTregimensontheprevalenceofanemiaoptimaldosingstrategiesfortheuseofepoetinalfaCost-benefitanalysesBiologyofAnemia,DifferentialDiagnosis,andTreatmentOptionsTheBiologyofHIV-RelatedAnemiaThecausesaremultifactorial:---HIVmaydirectlyaffect:bonemarrowstromalcellorcausecytokinesecretionTumornecrosisfactorandothercytokinesinhibithematopoiesisparvovirusB19infectionmedications,opportunisticinfections,neoplasms,nutritionalabnormalitiesstemmingfromanorexia,malabsorption,metabolicdisordersthatotherconditions,suchashemolysisorgastrointestinalbleeding,mayalsooccurinthesepatientsDifferentialDiagnosisbeingtreatedwithmultiplemedicationsmayhavemorethanoneco-morbidconditionrequiremultipleevaluationsdistinguishtheanemiaofchronicdiseasefromthatcausedbyirondeficiency:bothinalowserumironlevel,lowtotaliron-bindingcapacityandserumferritinlevels>100mg/L---unlikelytohaveirondeficiency;supplementwithironfor7–10days---re-evaluatetheanemiaTreatmentOptions※Treatmentshouldbechosentoaddresstheunderlyingcauseofthisdisorder※Bloodtransfusion---severeanemia,withahemoglobinlevelof<8g/dL.※Epoetinalfa---4–8weeks,itsefficacyandsafetyforpatientswithmildsymptomaticormoderateHIV-relatedanemia※Androgens---increaseproductionoferythropoietinwithanemiacausedbybonemarrowfailureHIV-AssociatedAutoimmuneHemolyticAnemiaThisreviewarticlediscussestheetiology,pathophysiology,clinicalfeatures,diagnosis,treatment,andcomplicationsofautoimmunehemolyticanemia(AIHA)associatedwithHIVinfection.ETIOLOGYAIHAresultsfromthedestructionoferythrocytesbyantibodies.TheetiologiesforAIHAarevariousincludingidiopathiccauses,drugs,infectiousagents,neoplasms,orautoimmunediseaseSeveralmechanismshavebeenpostulatedtoExplainwhyAIHAdevelopsinpatientswithAIDS?presenceoferythrocyteautoantibodiesorthepresenceofhypergammaglobulinemiamayresultinnonspecificcoatingofoverabundantimmunoglobulinG(IgG)toautologouserythrocytes?presenceofimmunecomplex-associatedIgG,maybindtoerythrocytesviaC3breceptors?abnormalB-cellregulationbyHIV-infectedTcells?InfectiousagentsassociatedwithAIDSmaybeassociatedwiththeproductionofautoantibodies?lymphomaCLINICALPRESENTATIONAnemia,pallor,mildjaundice,andsplenomegaly---30%AIHAcanbeclassifiedasmild,moderate,orsevere★Mildhemolyticanemiaischaracterizedbypositivedirectantiglobulintestresultsonly★Moderateanemiaischaracterizedbyanemiaandsplenomegaly★Severeanemiaischaracterizedbyfulminanthemolysiswithmarkedspherocytosis,hyperbilirubinemia,absentordecreasedlevelsofhaptoglobin,andhemoglobinuriaDIAGNOSISPositiveCoombs’testSerologicfindings:Typesofantierythrocyteantibodies---includethecoatingoferythrocytesbybothIgGandC3,orIgGaloneConcomitantcoldandwarmantibodiesTREATMENTmonitoredforpossibleprogressionofthehemolysisbloodtransfusion;corticosteroids,immunoglobulins,splenectomy,immunosuppressivetherapy,plasmapheresis,andzidovudine.COMPLICATIONS

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

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