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HIV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).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※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-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☆Ifthehemoglobinlevelislowerthannormal---ruleoutorcorrecttreatablecauses☆InitiateHAARTifwarranted☆Ifcorrectablecausesofanemiahavebeenruledoutandthehemoglobinlevelis<13g/dLinmenand<12g/dLinwomen---epoetinalfatherapyatadosageof40,000Uonceperweek.☆Anticipatedbenefitsofepoetinalfatreatment☆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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