溶血性貧血的介紹ppt課件.ppt

第六篇血液系統(tǒng)疾病 第六章溶血性貧血 弋磯山醫(yī)院血液內(nèi)科黃東平 溶血性貧血 HA 概述 定義臨床分類臨床表現(xiàn)發(fā)病機(jī)制與實驗室檢查診斷和鑒別診斷治療 一 定義 溶血是一組由于后天或先天的各種原因使紅細(xì)胞遭破壞壽命縮短的過程 HA系指紅細(xì)胞破壞超過骨髓造血代償功能而發(fā)生的一種貧血 如溶血發(fā)生而骨髓能代償時 臨床無貧血 稱為溶血性疾病 二 臨床分類 紅細(xì)胞自身異常所致的HA紅細(xì)胞外部異常所致的HA 一 紅細(xì)胞自身異常所致的HA 紅細(xì)胞膜異常遺傳性紅細(xì)胞酶的缺乏遺傳性珠蛋白生成障礙血紅素異常 紅細(xì)胞膜異常 遺傳性紅細(xì)胞膜缺陷遺傳性球形紅細(xì)胞增多癥 遺傳性橢圓形紅細(xì)胞增多癥 遺傳性棘性細(xì)胞增多癥 遺傳性口形細(xì)胞增多癥獲得性血細(xì)胞膜糖化肌醇磷酯 GPI 錨鏈膜蛋白異常 如PNH 遺傳性紅細(xì)胞酶的缺乏 戊糖磷酸途徑酶缺陷如G6PD缺乏癥等無氧糖酵解途徑缺陷如丙酮酸激酶缺乏癥等核苷代謝酶系 氧化還原酶系等缺陷等 遺傳性珠蛋白生成障礙 珠蛋白肽鏈結(jié)構(gòu)異常不穩(wěn)定血紅蛋白病 血紅蛋白病S D E等珠蛋白肽鏈數(shù)量異常 地中海貧血 血紅素異常 先天性紅細(xì)胞卟啉代謝異常如紅細(xì)胞生成性血卟啉病 原卟啉型 尿卟啉型和糞卟啉型鉛中毒可影響血紅素的合成發(fā)生HA 二 紅細(xì)胞外部異常所致的HA 免疫性HA血管性生物因素理化因素 免疫性HA 自身免疫性HA溫抗體型或冷抗體型 冷凝集型 D L抗體型 原發(fā)性或繼發(fā)性 SLE 病毒或藥物等0同種免疫性HA如血型不合的輸血反應(yīng) 新生兒HA 血管性 微血管病性HA如 TTP HUS DIC 敗血癥等瓣膜病 鈣化性主動脈瓣狹窄 人工心瓣膜和血管炎等血管壁受到反復(fù)擠壓 行軍性血紅蛋白尿 生物因素 理化因素 蛇毒 瘧疾和黑熱病等大面積燒傷 血漿中滲透壓改變和化學(xué)因素如苯肼 亞硝酸鹽等中毒 可引起獲得性高鐵血紅蛋白血癥而溶血 三 臨床表現(xiàn) 急性溶血 起病急 突然寒戰(zhàn) 高熱 頭痛 四肢酸痛等 面色蒼白 血紅蛋白尿和黃疸 嚴(yán)重者周圍循環(huán)衰竭和急性腎衰竭慢性溶血 起病慢 常有貧血 黃疸和肝脾腫大三個特征膽石癥 肝功能損害嚴(yán)重溶血時骨髓腔擴(kuò)大 X線骨皮質(zhì)變薄 骨骼變形 四 發(fā)病機(jī)制和臨床表現(xiàn) 紅細(xì)胞破壞和血紅蛋白降解紅系代償性增生紅細(xì)胞具有缺陷或壽命縮短 紅細(xì)胞破壞和血紅蛋白降解 血管內(nèi)溶血游離Hb升高 40mg L 結(jié)合珠蛋白降低 0 5g L 溶血停止3 4天后恢復(fù)正常尿常規(guī) 隱血陽性 尿蛋白陽性而紅細(xì)胞陰性Rous試驗慢性溶血時常陽性 紅細(xì)胞破壞和血紅蛋白降解 血管外溶血血清游離膽紅素升高尿常規(guī) 尿膽原增多 呈強陽性 膽紅素陰性24小時糞膽原和尿膽原增多 血管外溶血的一種特殊形式 無效性紅細(xì)胞生成原位溶血 紅系代償性增生 骨髓紅系代償性增生 粒紅比值減低或倒置RC升高外周血涂片可見有核紅細(xì)胞 嚴(yán)重溶血還可見幼粒細(xì)胞部分紅細(xì)胞可見和碎片 如Howell Jolly小體和Cabot環(huán) 紅細(xì)胞具有缺陷或壽命縮短 通過有關(guān)的實驗室檢查用放射性核素51Cr標(biāo)記紅細(xì)胞測定紅細(xì)胞壽命 HA壽命一般小于15天 五 診斷和鑒別診斷 診斷病史有急慢性溶血的臨床表現(xiàn)要確定血管內(nèi)還是血管外溶血Coombs試驗 鑒別診斷 貧血伴網(wǎng)織紅升高如失血性 缺鐵性和巨幼細(xì)胞貧血的恢復(fù)早期急性黃疸性肝炎肌紅蛋白尿先天性膽紅素代謝缺陷如家族性非溶血性黃疸 Gilbert綜合癥 幼紅幼粒細(xì)胞貧血伴輕度RC增多如骨髓轉(zhuǎn)移癌等 自身免疫性溶血性貧血 概述 是一種獲得性溶血性貧血 由于免疫功能紊亂產(chǎn)生自身紅細(xì)胞抗體 與紅細(xì)胞表面抗原結(jié)合 或激活補體使紅細(xì)胞加速破壞而致溶血性貧血 占溶血性疾病約1 3 國內(nèi)僅次于PNH 占溶血性疾病患者第二位 女性多于男性 以青壯年為多 AIHA分溫抗體型和冷抗體型 溫抗體型占80 溫抗體型AIHA 抗體為IgG或C3 少數(shù)為IgM 370C時最活躍為不完全抗體 吸附與紅細(xì)胞表面 致敏的紅細(xì)胞易被巨噬細(xì)胞所破壞 可形成球形紅細(xì)胞IgG和C3抗體同時存在時溶血最重 一 病因 原發(fā)性或特發(fā)性即原因不明的占45 繼發(fā)性或癥狀性有 淋巴增殖性疾病如慢淋 淋巴瘤 骨髓瘤等 風(fēng)濕病 SLE 類風(fēng)濕關(guān)節(jié)炎和潰瘍性結(jié)腸炎等 慢性炎癥 慢性肝病 潰結(jié) 非淋巴系腫瘤 卵巢囊腫 肝癌等 藥物 青霉素類 奎尼丁 甲基多巴 頭孢菌素和福達(dá)拉賓等 二 臨床表現(xiàn) 急性型多發(fā)生于兒童伴病毒感染 偶見成人 起病急 常有寒戰(zhàn) 高熱 腰背酸痛 嘔吐 嚴(yán)重時可伴休克 昏迷多數(shù)溫抗體型AIHA起病緩慢 成人多見 無性別差別 虛弱 頭昏為常見癥狀體征 皮膚黏膜蒼白 黃疸 輕度脾腫大 50 質(zhì)硬 中度肝腫大 30 三 實驗室檢查 血象 正細(xì)胞正色素性貧血 網(wǎng)織紅細(xì)胞增高 少數(shù)可達(dá)50 可見較多的球形紅細(xì)胞和幼紅細(xì)胞 紅細(xì)胞大小不等 粒細(xì)胞基本正常 急性溶血階段白細(xì)胞可增高 血小板多正常 10 20 合并免疫性血小板減少 稱Evans綜合癥 骨髓象 增生活躍 少數(shù)發(fā)生再障危象 骨髓增生不良 網(wǎng)織紅極度減少 但片尾部可見巨大的早幼紅細(xì)胞 三 實驗室檢查 Coombs試驗陽性分直接和間接試驗 是溫抗體型AIHA最重要和最具診斷意義的指標(biāo)免疫學(xué)檢查部分患者血清球蛋白增高 抗核抗體陽性 補體降低 淋巴轉(zhuǎn)化率降低 ASO陽性 ESR增快 RF陽性膽紅素升高 以間接膽紅素為主 尿糞膽原排出增多 紅細(xì)胞脆性增加51Cr標(biāo)記紅細(xì)胞壽命縮短 四 診斷 臨床表現(xiàn)實驗室檢查診斷依據(jù) 近4個月內(nèi)無輸血史或特殊藥物服用史 Coombs陽性結(jié)合臨床表現(xiàn)和實驗室檢查可確診 如Coombs陰性 但臨床表現(xiàn)較符合 腎上腺皮質(zhì)激素或脾切術(shù)有效 除外其他溶血性貧血特別是遺傳性球形紅細(xì)胞增多癥等可診斷抗人球蛋白試驗陰性的AIHA 原發(fā)性多為女性 年齡不限 臨床表現(xiàn)除溶血和貧血外無特殊癥狀 半數(shù)有脾腫大 1 3有黃疸和肝大 繼發(fā)性常伴有原發(fā)病的臨床表現(xiàn) 實驗室檢查 貧血程度不一 有時很嚴(yán)重 可爆發(fā)急性溶血危象 外周血可見多數(shù)球形紅細(xì)胞及數(shù)量不等的幼紅細(xì)胞 偶見吞噬紅細(xì)胞現(xiàn)象 網(wǎng)織紅細(xì)胞增多骨髓幼紅細(xì)胞增生象 偶見紅系輕度巨幼變再障危象時 RC極度減少 骨髓呈再生障礙 外周血象全血細(xì)胞減少Coombs陽性 主要為抗IgG和抗補體C3型 偶有抗IgA型 間接試驗可陽性或陰性 五 治療 糖皮質(zhì)激素脾切除免疫制劑貧血較重者應(yīng)輸洗滌紅細(xì)胞繼發(fā)性應(yīng)積極尋找病因 治療原發(fā)病 冷抗體型AIHA 冷凝集素綜合癥陣發(fā)性冷性血紅蛋白尿冷抗體為D L IgG 抗體 多繼發(fā)病毒和梅毒感染 常遇冷發(fā)作血紅蛋白尿 伴發(fā)熱 腹痛 腰背酸 惡心嘔吐等 反復(fù)發(fā)作者可有脾大 黃疸 含鐵血黃素尿等 ANEMIASOFEFFECTIVEERYTHROPOIESIS CLS843ADVANCEDCLINICALHEMATOLOGYRaymondL Olesinski 2001UniversityofKentucky AnemiasofEffectiveErythropoiesis ModuleObjectives AttheendofthismoduleyoushouldbeabletoDefinehemolyticanemia HA ExplainthemeaningofIntravascularhemolysisExtravascularhemolysis AnemiasofEffectiveErythropoiesis ModuleObjectives DescribewhatperipheralbloodfindingsareconsistentwithaHAListwhatlaboratoryfindingsareassociatedwithspecificHAs AnemiasofEffectiveErythropoiesis ModuleObjectives IdentifywhatlaboratorytestsareusedtomakeadiagnosisofspecificHAsDiscusstheSpecimenrequirementsLimitationsoflaboratorytestsusedtodiagnoseHA AnemiasofEffectiveErythropoiesis ModuleObjectives Discussspecificsofspecimencollection handling storage andpreparationforthePlasmahemoglobinHaptoglobinOsmoticfragilitySugarwatertestHam sacidifiedserumtest AnemiasofEffectiveErythropoiesis ModuleObjectives Explainthephysiologictheoryrelevanttothetest procedureforthePlasmahemoglobinHaptoglobinOsmoticfragilityFluorescentspottestforpyruvatekinasedeficiency AnemiasofEffectiveErythropoiesis ModuleObjectives G6PDfluorescentspottestQuantitativeG6PDtestSugarwatertestHam sacidifiedserumtest AnemiasofEffectiveErythropoiesis ModuleObjectives Explaintheprincipleofthetest procedureforthePlasmahemoglobinHaptoglobinOsmoticfragilitySugarwatertestHam sacidifiedserumtest AnemiasofEffectiveErythropoiesis ModuleObjectives Identifythediseasemanifestation clinicalcorrelationforthePlasmahemoglobinHaptoglobinOsmoticfragilityFlorescentspottestforpyruvatekinasedeficiency AnemiasofEffectiveErythropoiesis ModuleObjectives G6PDflorescentspottestQuantitativeG6PDtestSugarwatertestHam sacidifiedserumtest ClassificationHemolyticAnemia Inheritedvs acquiredIntrinsicvs extrinsicdefectMCV RDWAcutevs chronic SitesofHemolysisHemolyticAnemia Extravascular SeeFigure16 1 Destructionoccursinreticuloendothelialsystem mostlythespleen HemoglobinreleasedtomacrophagesSenescentRBCCullingPitting SitesofHemolysis Intravascular SeeFigure16 2 DestructionoccurswithinthebloodvesselsHemoglobinisreleasedtotheplasma SitesofHemolysis FactorsleadingtointravascularhemolysisComplementcoatingArtificialsurfacesMicroangiopathicprocessesInfection SitesofHemolysis Factorsleadingtointravascularhemolysis continuedBurnsLiver kidneydiseaseChemicalsPhysicaltrauma Catabolism Seefigure16 1 PrimaryLaboratoryInvestigation HemogramfindingswillvarydependingonthespecifictypeofanemiaThemostimportantfindingisanincreasedreticulocytecountthatcontributestoanRPI 3 PrimaryLaboratoryInvestigation TheincreasedreticulocytecountisusuallyaccompaniedbyperipheralsmearRBCpolychromasia Morphology Pathophysiology ClinicalRelevance RedBloodCellMorphologyInter relationshipTriad MorphologyinHA MorphologyspecifictothetypeofHAmaybepresent e g spherocytes elliptocytesandstomatocytes SecondaryLaboratoryInvestigation Decisionsaboutwhatprocedurestouseforsecondary orfollow up investigationarebasedonthefindingsofthehemogramandmorphology SecondaryLaboratoryInvestigation ChemistryBilirubin Increasedunconjugatedbilirubinisindicativeofhemolysis SecondaryLaboratoryInvestigation Chemistry continuedHaptoglobinCarriesfreeplasmaglobinDecreasedlevelsareindicativeofhemolysisMaybeincreasedininflammationmaskinghemolysis SecondaryLaboratoryInvestigation Chemistry continuedIncreasedfreeplasmahemoglobinIncreasedlacticdehydrogenaseUrinalysisHemoglobinuriaormethemoglobinuriaHemosiderinuriaUrobilinogen SurveyofHAbyType HereditaryAcquired HereditaryHA MembraneabnormalitiesEnzymopathiesPlasmaconstituentabnormalities RBCMembraneStructure MembraneAbnormalities SpherocytosisElliptocytosisPyropoikilocytosisStomatocytosis MembraneAbnormalities Seefigure17 1 Spleen EffectsonRBCs HereditarySpherocytosis Defect RBCproteindefectsaffectingspectrinPathophysiologyIncreasedNa permeability RBCrigidity DestructioninspleenTesting IncreasedosmoticfragilityIncubatedosmoticfragility HereditarySpherocytosis Seefigures17 2and3 SpherocyteMorphology Pathophysiology LacksareaofcentralpallorAdditionalcausesImmunologicreactionPhysicaltraumaUsually 6 5 mdiameterMicrospherocytes 4 mdiameter HereditaryElliptocytosis Defect Unknown spectrindefects PathophysiologyIncreasedNa efflux Hemoglobinbipolarization Cholesterolpolarization RBCrigidity Destructioninspleen Ellipto OvalocyteClinicalRelevance Hereditaryellipto orovalocytosis 25 ofallRBCs Macro ovalocytesseeninmegaloblasticanemiasNon specificfindinginothertypesofanemia 25 ofallRBCs HereditaryElliptocytosis Testing MorphologyIncreasedosmoticfragility HereditaryElliptocytosis Slidesnotshown SeeFigure8 7 p 91 ClinicalHematology HereditaryPyropoikilocytosis Defect SpectrindefectPathophysiology RBCrigidityDestructioninspleenTesting Increasedthermalsensitivitytest HereditaryPyropoikilocytosis Slidesnotshown SeeFigure8 15 p 95 ClinicalHematology HereditaryStomatocytosis Defect UnknownPathophysiology IncreasedinfluxofRBCH2ORBCrigidityDestructioninspleen StomatocyteMorphology Pathophysiology Slit likeareaofcentralpallor HereditaryStomatocytosis Testing MorphologyStomatocytosis IncreasedosmoticfragilityXerocytosis numeroustargetcells Decreasedosmoticfragility EnzymopathiesHemolyticAnemia PyruvatekinasedeficiencyGlucose 6 phosphatedehydrogenasedeficiency EnzymopathiesHemolyticAnemia Seefigure17 5 EnzymopathiesHemolyticAnemia Laboratoryfindings G6PDdeficiencyBitecellsHeinzbodiesSpottest StrongflourescenceindicatesnormalG6PDactivity BiteCellsMorphology Pathophysiology CrateredRBCCratersformedbyremovalofHeinzbodiesformedfromunstablehemoglobin EnzymopathiesHemolyticAnemia Slidesnotshown SeeFigure17 6 p 262 ClinicalHematology EnzymopathiesHemolyticAnemia Laboratoryfindings PKdeficiencySpottest LossofflourescenceindicatesnormalPKactivity PlasmaConstituentAbnormalities Abetalipoproteinemia AKAhereditaryacanthocytosisLecithin CholesterolAcyltransferaseDeficiency Numeroustargetcells TargetCell Codocyte Pathophysiology IncreasedcholesterolorphospholipidonRBCmembraneIncreasedsurfacearea volumePre crystallinestateofhemoglobinC TargetCell Codocyte Slidesnotshown SeeFigure8 11 p 92 ClinicalHematology EchinocyteMorphology 30short bluntprojectionsevenlydistributedoverthecellsurfaceA K A burrcell crenatedRBC seaurchincellWetmountcomparison AcanthocyteMorphology 5 12thornlikespiculesunevenlydistributedoverthecellsurfaceProjectionsmaybeclubshapedordrumstickshaped spurcells AcquiredHemolyticAnemia ExtracorpusculardefectsAbnormalbloodvesselstructureMechanicalinjuryMiscellaneousIntracorpusculardefectsImmuneprocesses ExtracorpuscularDefects MicroangiopathichemolyticanemiaDisseminatedintravascularcoagulation DIC Hemolyticuremicsyndrome HUS Thromboticthrombocytopenicpurpura TTP SchistocyteMicroangiopathicTrauma SchistocyteMicroangiopathicTrauma Slidesnotshown SeeFigure8 12 p 94 ClinicalHematology Intracorpuscular PNH Majordefect ComplementsensitiveRBCsinacidifiedplasmaenvironmentPathophysiology ExtravascularlysisofaffectedRBCoccurringduringtheeveninghoursleadingtoachronichemolyticanemia Intracorpuscular PNH SecondaryinvestigationScreeningtest SugarwatertestIncreasedhemolysisinPNHDefinitivetest Ham sacidifiedserumtest SeeTable18 1 ClinicalHematology p 269 Significantlysisintubescontainingacidifiedserumandcomplement ModuleObjectives BloodLossAnemia AttheendofthismoduleyoushouldbeabletoDescribethenaturalcourseofacutebloodlossanemiaDescribethechangesinlaboratorytestresultsthatcanbeexpectedinacutebloodlossanemia ModuleObjectives BloodLossAnemia Explainthetestresultsexpectedinchronicbloodlossanemia LaboratoryFindingsBloodLossAnemia AcutebloodlossanemiaNochangeinCBCparametersinfirstfewhours3 4hoursHb HctPossible WBCcountPossible LaboratoryFindingsBloodLossAnemia Acutebloodlossanemia continued12 24hoursHb Hct reflectingdegreeofbloodlossProbableleukocytosisPossiblethrombocytosis LaboratoryFindingsBloodLossAnemia Acutebloodlossanemia continued3 5daysPossible MCVPossible reticulocytecountPossible RPI 3 LaboratoryFindingsBloodLossAnemia SeeTable20 2 LaboratoryFindingsBloodLossAnemia Findingsandcourseinchronicbloodlossanemiaaresimilartoirondeficiencyanemia LaboratoryFindingsBloodLossAnemia Morphology AcutebloodlossFirstfewhoursnosignificantchanges 3 4hoursPossibleleftshiftPossibleNRBCs LaboratoryFindingsBloodLossAnemia Morp