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《內(nèi)科學(xué)》全冊(cè)配套教學(xué)課件idiopathicthrombocytopeniapurpura

特發(fā)性血小板減少性紫癜概述1、定義：免疫介導(dǎo)—血小板過度破壞—出血性疾病。原發(fā)免疫性血小板減少癥（primaryimmunethrombocytopenia)(immunethrombocytopeniaITP)發(fā)?。杭s占成人出血性疾病30%,兒童出血性疾病60%， 5～19/10萬人，女:男1:1。診斷：排除性診斷，缺乏特異性。治療：非特異，有效率60-70%。

Idiopathicthrombocytopenicpurpura

(ITP)HarringtonetalJLabClinMed38:1,1951Incidence:~3newcases/10106person-yrsPrevalence:~20cases/10106person-yrs121086420<1818–2425–3435–4445–5455–5959–6465–7475–8485–100TotalAge(yrs)Meanannualincidence

(per10106

person-yrs)FemalesMalesBrJHaematol2009;92:1165–1171.依年齡和性別的ITP年發(fā)病率（n=1145）發(fā)病機(jī)制由體液和細(xì)胞免疫介導(dǎo)：血小板破壞過多；抗血小板抗體。血小板生成不足：巨核細(xì)胞數(shù)量和質(zhì)量異常。TPO水平相對(duì)不足巨核細(xì)胞成熟障礙和產(chǎn)板不良NEnglJMed,2002,346(13):995-1008臨床表現(xiàn)臨床上以不同程度和部位的出血為主要表現(xiàn)（一）起病1、隱匿2、多見于育齡婦女，起病緩慢，無明顯誘因。臨床表現(xiàn)（二）出血傾向1、皮膚粘膜出血2、內(nèi)臟出血較少見，感染可加重出血。顱內(nèi)出血是致死的主要原因。3、鼻衄、月經(jīng)過多在部分慢性ITP患者可為唯一臨床癥狀。關(guān)于ITP患者的出血ITP患者主要表現(xiàn)為皮膚粘膜出血（瘀點(diǎn)或紫癜），PLT>30109/L時(shí)很少有明顯出血。嚴(yán)重內(nèi)出血或致命性顱內(nèi)出血十分罕見，有時(shí)發(fā)生于有合并癥的老年患者。慢性ITP患者（PLT<30109/L）致命性出血的年發(fā)生率1.6~3.9%。這一危險(xiǎn)性隨年齡而異，<40歲者年發(fā)生率0.4%，而>60歲者年發(fā)生率可達(dá)13%。ArchinternMed2000;160(11):1630-8臨床表現(xiàn)（三）乏力（四）一般無脾大，但部分病程超過半年的慢性型ITP患者可有輕度腫大。（五）血栓形成傾向（六）一般無貧血，若出血量多，可有貧血，且貧血與出血平行。實(shí)驗(yàn)室檢查（一）血液檢查1、血小板計(jì)數(shù)：減少2、血小板平均體積偏大3、出血時(shí)間延長(zhǎng)4、血小板功能一般正常5、若出血嚴(yán)重，可有程度不等的貧血。實(shí)驗(yàn)室檢查（二）骨髓檢查

巨核細(xì)胞分化：

原巨核細(xì)胞→幼稚型巨核細(xì)胞→顆粒型巨核→產(chǎn)板型巨核細(xì)胞。正常以產(chǎn)板巨為主。

骨髓檢查1、巨核細(xì)胞正?；蛟龆?，2、巨核細(xì)胞發(fā)育成熟障礙：

體積變小幼稚巨核細(xì)胞增多

產(chǎn)板型巨核細(xì)胞減少。2、粒系及紅系正常，

若出血嚴(yán)重則紅系增生，

鐵染色可顯示外鐵消失，

鐵粒幼細(xì)胞＜15%。診斷及鑒別診斷（一）ITP診斷是排除性診斷1、廣泛出血累及皮膚、粘膜及內(nèi)臟。2、至少2次檢查BPC減少，血細(xì)胞形態(tài)無異常3、脾一般不增大4、骨髓檢查：巨核細(xì)胞增多或正常，有成熟障礙。5、除外其他繼發(fā)性血小板減少癥診斷及鑒別診斷與繼發(fā)性血小板減少癥鑒別：1）再障2）白血病3）SLE4）脾功能亢進(jìn)5）TTP6）藥物性免疫性血小板減少。診斷ITP的特殊檢查血小板抗體檢測(cè)MAIPA法檢測(cè)抗原特異性自身抗體，可以鑒別免疫性與非免疫性的血小板減少。血小板生成素水平（TPO）水平檢測(cè)

鑒別血小板生成減少（TPO水平升高）和血小板破壞增加（TPO水平降低）分型1.

新診斷的ITP：ITP確診3個(gè)月以內(nèi)。2.

持續(xù)性ITP：確診后3~12個(gè)月PLT持續(xù)減少，包括未自發(fā)緩解或停止治療后不能維持完全緩解的患者。3.

慢性ITP：血小板減少持續(xù)>12個(gè)月。分型4.

重癥ITP：血小板<10×109/L，存在需要治療的出血癥狀或治療過程中發(fā)生新的出血，需采用其它升高PLT的藥物治療或增加現(xiàn)有治療藥物的劑量。5.

難治性ITP：同時(shí)滿足以下3個(gè)條件：①脾切除后無效或復(fù)發(fā)；

②仍需要治療以降低出血危險(xiǎn)性；

③再次除外其它原因引起的血小板減少癥，確診為ITP。治療（一）一般治療，對(duì)癥治療。（二）觀察無明顯出血，血小板＞30X109/L，無手術(shù)、創(chuàng)傷

治療指證不需治療：若PLT>20~30109/L、無出血表現(xiàn)，勿需治療，僅觀察即可。需要治療：PLT<20~30109/L，或<50109/L伴有粘膜出血（或出血危險(xiǎn)如高血壓、消化性潰瘍等）。需要住院：PLT<20109/L伴粘膜出血，或有嚴(yán)重出血、危及生命出血。安全操作所需血小板數(shù)口腔科檢查10×109/L拔牙、補(bǔ)牙

30×109/L小手術(shù)、正常陰道分娩

50×109/L大手術(shù)、剖腹產(chǎn)

80×109/LBrJHaematol,

2003;120:574-596.治療

（三）首次診斷ITP的一線治療1、首選糖皮質(zhì)激素

（1）劑量與用法：Pred1mg/kg/d，BPC正常后，1個(gè)月快速減至最小維持量5-10mg。無效者4周停藥。

（2）副作用：血壓、血糖，預(yù)防感染治療2、靜脈輸注丙種球蛋白（1）ITP急癥的處理（2）不能耐受糖皮質(zhì)激素或脾切前準(zhǔn)備（3）有糖皮質(zhì)激素使用禁忌癥（4）400mg/kg/dX5天治療（四）ITP的二線治療脾切除1、適應(yīng)證：（1）正規(guī)糖皮質(zhì)激素治療無效，遷延6月以上（2）強(qiáng)的松維持量＞30mg/d（3）有糖皮質(zhì)激素使用禁忌癥治療2、禁忌證：（1）年齡＜2歲（2）妊娠期（3）因其他疾病不能耐受手術(shù)3、療效：有效率70%～90%治療2、藥物治療（1）抗CD20單克隆抗體（2）血小板生成藥物（3）長(zhǎng)春新堿（4）環(huán)孢素A（5）其他ManagementofITPAlternativetherapy(individualization):AgeofpatientSeverityofpresentationPlateletcountPrimaryrefractoryorrelapsedLengthoftimepriortorelapse規(guī)范治療ITP治療方案觀察Plt>30109/L地塞米松40mgpo4d；或甲強(qiáng)1g/div3d。每2w一療程、共三療程新診斷ITPPlt<30109/L，伴出血CTX200-400mgiv.2/w6~8次（或CTX1giv.1/3w3次）VCR1mgiv.drip1/w3~4次CsA

3~6mg//kg/d，監(jiān)測(cè)血藥濃度有效者減量維持至少6月美羅華375(或100mg)/m2，1/w4次有效者可每3-6月375(或100)mg/m2，維持rhTPO300U/kg/d，S.C.14d或Plt>50109/L停用非常規(guī)治療：移植無效時(shí)依情選其它方案可選任一方案，達(dá)那唑0.2，Bid~Tid，至少3月有效者減量維持治療3月Plt<30109/LPlt<30109/L潑尼松1mg/kg/d21d潑尼松漸減量維持治療3月Plt>30109/L持續(xù)性/慢性ITP脾切除（包括副脾）有效者CTX100mg、2~3次/w并漸減量維持，總劑量<10g有效者可每周給藥1-2次維持重型ITP的搶救性治療：若Plt<10109/L或嚴(yán)重出血，除激素外，可給予血小板輸注、IVIg或rhTPO不接受或無效治療

（六）急癥處理（1）BPC＜20×109/L（2）出血廣泛嚴(yán)重（3）疑有或已發(fā)生顱內(nèi)出血者（4）近期將實(shí)施手術(shù)或分娩者治療（1）血小板懸液輸注（2）靜注丙種球蛋白（3）大劑量甲潑尼龍簡(jiǎn)歷

彭志剛，男，醫(yī)學(xué)博士，教授，碩士研究生導(dǎo)師。廣西醫(yī)科大學(xué)第一附屬醫(yī)院大內(nèi)科副主任、內(nèi)科學(xué)教研室副主任、血液內(nèi)科副主任，中華醫(yī)學(xué)會(huì)血液學(xué)分會(huì)第七、八屆全國青年委員，中華醫(yī)學(xué)會(huì)血液學(xué)分會(huì)第七、八屆“白血病和淋巴瘤學(xué)組”委員，現(xiàn)任廣西醫(yī)學(xué)會(huì)血液學(xué)分會(huì)主任委員。主要研究方向?yàn)檠耗[瘤的臨床及實(shí)驗(yàn)研究。

LeukemiaPengZhigangDep.Hematology，

GuangxiMedicalUniversityConceptofleukemiaDefinitionLeukemiaisamalignantClonalheamotopoieticstemcells

disorderProliferationisoutofcontrolandapoptosisisinhibited.Leukemiacellisclonedandaccumulatedinagreatquantity,thenormalhemapoiesisisihibited.DifferentiationofHSCisblocked.LeukemiacellsarestoppedonadifferentiationstageofHSC&lackofthenormalfunction.ExtramedullaryinvolvementandmetastasisHematopoiesisPLURIPOTENTSTEMCELLCOMMITTEDPROGENITORCELLRECOGNIZABLEBONEMARROWPRECURSORCELLMATUREBLOODCELLmyeloblastmonoblastpronormoblastredcellneutrophilmonocytebasophilplateletCFU-BasoCFU-EosCFU-GMBFU-E/CFU-Eeosinophilpre-Tpre-BmyeloidprogenitorcelllymphoidprogenitorcelllymphoblastlymphoblastT-cellB-cell&plasmacellMIXEDPROGENITORCELLCFU-MegmegakaryocytepluripotentstemcellMyeloidmaturationmyeloblastpromyelocytemyelocytemetamyelocytebandneutrophilMATURATIONAdaptedandmodifiedfromUVawebsitemalignantblooddisorderspathophysiologyClinicalmanifestationHSCdifferentiationisblockedNormalbloodcellsaredecreasedThefunctionofBloodandimmunesystemareshortof.Anemia,fever,hemorrhageAbnormalmorphologypicturesofbloodandbonemarrow.

Proliferationisoutofcontrol,apoptosisisinhibited.Leukemiacellisaccumulatedinagreatquantity.LeukocytesandLeukostasis(白細(xì)胞淤滯)Liver,spleen,lymphnods,skin,CNSetc.areinfiltratedanddysfunctionalfrequently.Classificationofleukemias

Dependingonthedfferentiation

andthenaturalcourseofthedisease,Itcanbedividedintotwokinds:AcuteLeukemiaprogressesquicklycharacterizedbytheproliferationofundifferentiatedcellsinthebonemarrowLifespan<3-6msChronicLeukemiaslowerprogressionuncontrolledexpansionofmaturecellsLifespan>12msClassificationofleukemiasAcuteChronicMyeloidoriginLymphoidoriginAcuteMyelogenousLeukemia(AML)AcuteLymphoblasticLeukemia(ALL)ChronicMyelogenousLeukemia(CML)ChronicLymphoblasticLeukemia(CLL)AccordingtoKindofcellcanbedividedinto:

Epidemiology:incidenceIncidence:3-4/105

，increasewithyears?distributionoftype:acute>chronic,AML>ALLSpecialdistribution:

Sexman：female＝1.81：1AgeALL,adolescent80％<20y;AML,adultCML,20~50yearsold;CLL,50~70yearsoldAreaadultTlymphocyticleukemiaCML,easterncountriesCLL,westerncountries

Epidemiology:mortality2.51/105Areacity>thecountrysideChina<Singapore<Japan<USA<unitedKingdom<Sweden(7.5～9/105)Inorderofthemortalityofmalignanttumorsin1～14y，leukemiaismosthighin15～44y，leukemiaisthirdhigh(<stomachCa<liverCa)inallperson,leukemiaissixth(male)oreighthhigh(female)EtiologyMostcasesarisewithnoclearcausesomeacceptedriskfactorsforleukemogenesisEtiologyBiologicfactors:

virus:HTLV-1canresultinAcuteTlymphomaicleukemia.ImmunologydefectEtiologyPhysicalfactors

radiationexposure:ionicradiation,x-ray

1、atombomb2、highdoseXradiotherapy、

32PtherapyEtiologyChemicalfactorsChemicalexposure:benzenepetroleumPesticideOtherenvironmentalexposureshairdyessmokingPriorchemotherapy

alkylatingagents(cyclophosphamideandmelphalan)TopoisomeraseIIinhibitors,doxorubicinandmitoxantrone

EtiologyGeneticdisorders:

DownsyndromeBloomsyndromeFanconi’sanemiaataxia-telangiectasiaWiskott-AldrichsyndromeInidenticaltwins

fromotherblooddisordersMyeloproliferativeDisease(MPD)chronicmyeloidleukemia(CML)polycythemiavera(PV)primarythrombocythemia(PT)myelofibrosis(MF)myelodysplasticsyndrome(MDS)paroxysmalnocturnalhemoglobinuria(PNH)lymphomaormyelomaEtiologyPrinciplesofleukemogenesisamultistepprocessThemutationofgene(ras,myc)resultintheproliferationoftheleukemiccloneSomegeneticchangesresultindifferentiationblockedatanearlystageAcuteLeukemias

Classification(FABsystem)

AML（M1）

AML(M2)

APL（M3）

AML（M4）

AML（M4EO）

AML（M5）

AML（M6）

AML（M7）ALL:FABClassificationL1-Smallcells;subtyperepresents25-30%ofadultcasesL2-Largeandirregularnuclearshape,andnucleolusoftenlarge;subtyperepresents70%ofcases(mostcommon)L3–veryLarge;subtyperepresents1-2%ofadultcases

ALL（L1）

ALL（L2）

ALL（L3）Classification（二）WHOClassification

MICM分型

morphology:形態(tài)學(xué)FAB分型

immunology:免疫學(xué)用CD抗原單克隆抗體分型

cytogenetics:細(xì)胞遺傳學(xué)染色體分型

molecularbiology:分子生物學(xué)基因分型ClinicalFeaturesdecreaseinnormalhematopoiesisaccumulationofblastcellsinothersites:infiltration

ClinicalFeaturesAnemia

(RBC↓)

?

pallor,weakness,fatigue,dyspnea,tachycardiaClinicalFeaturesbleedingPLT↓

?skin,purpura,mucosalbleeding,epistaxis,menorrhagia?life-threatening:brainbleeding?associatedwithDIC(promyelocyticleukemia)

ClinicalFeaturesInfections:

neutrophil↓

immune↓

?URI,gingivitis,pharyngitis,bronchitis

?pneumonitis,septicemia

?pathogens:gram-negative;fungusClinicalFeaturesdecreaseinnormalhematopoiesisaccumulationofblastcellsinothersites:infiltration

ClinicalFeaturesenlargementofliver,spleen,lymphnodes,

especiallyALLClinicalFeaturesbonepain,sternumtendernesschloroma/granulocyticsarcoma,Spinalcolumnororbit:exophthalmos,diplopia,blindnessClinicalFeaturesgumhypertrophySkin:rashes,palpable,hard,indigonodeClinicalFeaturesCNS-L:

oftenoccurredinALL,headache,dizziness,vomiting,neckrigidityClinicalFeaturestestisoftenoccurredinALL,TesticularpainlessenlargementanyorganLaboratorystudiesBlood：

WBCusuallyelevated,butcanbenormalorlow,WBC<1×109/L(hypoleukocytosis);>10×109/L(hyperleukocytosis)blastsarepresentanemia(normocytic),immatureRBCmaybepresentPLT↓thrombocytopeniaLaboratorystudiesBonemarrowaspirationnecessaryfordiagnosisusefulfordeterminingtypeusefulforprognosisLaboratorystudies

BonemarrowaspirationProliferative(mostcase);hypoplastic(10%)WHO:blasts>20%Auer‘srods(+)inAMLerythropoiesis↓megakaryocytopoiesis↓leukemiacells(showAuer’srods)

Laboratorystudies

Cytochemistry:

主要用于協(xié)助形態(tài)鑒別各類白血病常見AL的細(xì)胞化學(xué)鑒別急淋白血病(ALL) 急粒白血病 急性單核細(xì)胞白血病 過氧化物酶(POX)（－）分化差的原始細(xì)胞（－）～（＋）（－）～（＋）分化好的原始細(xì)胞（－）～（+++）

糖原PAS反應(yīng)（＋）成塊（－）或（＋），（－）或（＋）呈彌漫或顆粒狀彌漫性淡紅色 性淡紅色或顆粒狀

非特異性脂酶(NSE)（－）（－）～（＋）（＋）NaF抑制≥50%NaF抑制＜50%

LaboratorystudiescytochemicalstainsPeroxidasestain:AMLNonspecificesteraseandinhibitedbysodiumfluorid:M4,M5Periodicacid-Schiff(PAS)stain:ALLLaboratorystudiesImmunophenotypingCytogenetics表6-9-2白血病免疫學(xué)積分系統(tǒng)（EGILL，1998）分值B系T系髓系2

CyCD79aCyCD22CyIgM

CD3TCRa/BTCRr/B

CyMPO1

CD19CD20CD10

CD2CD5CD8

CD117CD13CD33CD650.5

TdTCD24

TdTCD7CD1a

CD14CD15CD64IMMUNO-PHENOTYPING

mab M1 M2 M3 M4 M5 M6 M7CD13 + + + + + - -CD33 + + + + + - -CD14 - ± - + + - -CD41 - - - - - - +Ret - - - - - + -Lectoferrin- + - + - - - CD19 CD7 HLA-DR CD3 MPO T - + - + - B + - + - -ImmunophenotypingAccordingtoImmunophenotypeofleukemia,ALis

dividedintofourtypess:1acuteundifferentiatedleukemia

（AUL）2Acutemixedlineageleukemia

3(1)M+ALL;(2)L+AML4Asinglephenotype:(1)ALL;(2)AML表6-9-3AML常見的染色體和分子學(xué)異常的意義預(yù)后等級(jí)細(xì)胞遺傳學(xué)（染色體）分子生物學(xué)異常良好t(15;17)（q22;q12）APL(PML/RARa)t(8;21)（q22;q22）AMLM2a(AML1/ETO)inv(16)（p13q22）/t(16;16)（p13;q22）

AMLM4Eo(CBFB/MYH11)正常核型伴有孤立的NPM1突變中等正常核型、孤立的+8、孤立的t(9;11)（p22；q23）、其他異常t(8;21)或inv(16)伴有c-kit突變不良復(fù)雜核型(≥3種)，-5、-7、5q-、7q-、11q23異常，除外t(9;11)、inv(3)、t(3;3)、t(6;9)、t(9;22)、正常核型伴有單獨(dú)的FLT3-ITD表6-9-4ALL常見染色體和分子學(xué)異常的檢出率染色體核型基因發(fā)生率（成人）發(fā)生率（兒童）超二倍體亞二倍體

--

7%2%

25%

1%t(9;22)（q22;q22）：Ph+t(12;21)（p13;q22）t(v;11q23)t(1;19)

BCR-ABL

TEL-AML1MLLE2A-PBX1

25%2%10%3%

3%22%8%5%t(5;14)（q31;q32）t(8;14)t(2;8)t(8;22)t(1;14)（p32;q11）t(10;14)（q24;q11）t(5;14)（q35;q32）

IL3-IGHc-myc

TAL1

HOX11HOX11L2

＜1%4%12%

8%1%

＜1%2%7%

1%3%

ChromosometranslocationFusiongeneM2t(8;21)AML1/ETOM3

t(15;17)PML/RARM4inv(16),t(16;16)CBF/MYH11M5t(4;11),11q23MLLabnormalitesALL(15%)L3t(9;22)t(8;14)BCR/ABLMYC,IgHrearrangementCommonCytogeneticAbnormalitiesinAMLandALLLaboratorystudiesChemistry:LDHand,UA↑DIC:APTT↑,PT↑,fibrinogen↓LaboratorystudiesChemistryCSFofGNS-L:

1,spinalfluidpressure↑（＞200mmH2O）2,WBC↑（＞0.01×109/L）3,Protein↑（＞450mg/L）4,blastspresentinthespinalfluid,

DiagnosisClinicalfeaturesBMaspiration:morphology,cytochemicalstaining,immunophenotyping,cytogenetics,molecularbiologyDifferentialDiagnosismyelodysplasticsyndromes(MDS)Infections:infectiousmononucleosisbonemarrowrecoveringfromacuteagranulocytosismegaloblasticanemiaTreatmentEliminateofhyperleukocytosis:

leukapheresishydroxyureahydratedchemotherapyLeukostasisaccumulationofblastsinmicrocirculationwithimpairedperfusionlungs: hypoxemia,dyspnea,pulmonaryinfiltratesCNS: stroke,dizziness,stupor,intracerebralhemorrhageonlyseenwithWBC>>50x109/LAvoidoftumorlysissyndromes:(Hyperkalemia;hyperphosphatemia;hyperuriemia;

hypocalcemia

combinationofhydration,allopurinol,andalkalinizationofurinewithsodiumbicarbonateTreatment

SupportivecareReplacementofbloodproducts:packedredbloodcells,platelets,freshfrozenplasma

Antibiotics

UseofgrowthfactorsMetabolicmanagementTreatment:Chemotherapy

aimsoftreatmenteliminateabnormalcloneallowrepopulationofmarrowwithnormalhemopoieticcellsTherapeuticprincipleofALearlycombinefullintervalrepeatChemotherapy

TwoorthreephasesRemissioninduction(inductionchemotherapy)ConsolidationtherapyMaintenancechemotherapyInductionchemotherapyaims–CRCompleteremission

:

nosignsorsymptomsofthediseasenormalperipheralbloodcellcountnormocellularmarrowwithlessthan5%blastsinthemarrowInaddition,therearenoextramedullaryinfiltration.ConsolidationtherapyConsolidationtherapy

istreatmenttoclearresidualleukemiawhenpatientsareinmorphologicremission.Molecularmarkersofresidualdiseasecanoftenbedetectedafterinductionchemotherapy,whichindicatestheneedforfurthertreatment.

MaintenancechemotherapyMaintenancechemotherapyisusedprimarilyinALLandAPL,sincelowdoseantileukemicagentsadministeredover18-24monthscanpreventrelapse.

TreatmentofALLRegimen

induced

remissionVP (classical)

VCR2mg+NS20ccVqw

Prednisone20~30mg/dp.oCR50%butrelapseeasily2.VDLPVCR1～2mg＋NS20ccVqw(1,8,15,21d)

DNR30～40mgVgttqd1～3d,15～17d

Pred40mg～60mgp.o1～14d

L-ASP10,000uVgtt19－28dCR80~90%VDLCP:TALL+CTX;Ph+ALL:+TKIConsolidationtherapyofALLTheconsolidationwithalternatingcyclesofhigh-doseAra-C(HDAC)andetoposidewithhigh-doseMTXHSCTCNS-LprophylaxisTheincidenceofCNSrelapseismuchhigherinpatientswithALLthaninthosewithAML;amongpediatricALL,therateofCNSrelapsewas20%inthefirstyear.CNS-LprophylaxisPatientswithALLrequirepreemptivetherapyforoccultCNSdiseasewitheither(1)intrathecalMTXandAra-Ccombinedwithcranialirradiation.(2)high-dosesystemicAra-CInductiontherapyofAML(noAPL)

regimensidarubicin+cytarabine(IA)daunorubicin+cytarabine(DA)CR50-80%HACR60-65%mitoxantrone+cytarabine(MA)TreatmentofAPLAPLismostcommonlyassociatedwithDICandfibrinolysis.95%ofcases,cytogeneticstestingrevealst(15;17)(q21;q11).MolecularstudiesrevealthePML/RARarearrangementATRAorArsenicTrioxideisthefirstchoiceretinoicacidsyndromeischaracterizedbyfever,weightgain,pleuralandpericardialeffusions,andrespiratorydistress.ConsolidationtherapyofAML(noAPL)good-riskAML,ie,t(8;21),16(inv16),

araCat3g/m2twiceadayondays1,3,and5ofeachcycle,repeatedmonthlyfor4consolidationcycles.Transplantationshouldbereservedforpatientswhorelapse.

ConsolidationtherapyofAML(noAPL)intermediate-riskcontroversial.Somereferpatientsinfirstremissionfortransplantationothersgiveconsolidationchemotherapywithhigh-dosearaCfor4coursesandreservetransplantationforpatientswhorelapse.ConsolidationtherapyofAML(noAPL)high-riskTheyarerarelycuredwithchemotherapyTheyshouldbeofferedallo-transplantationinfirstremission.

TreatmentofAPLconsolidationtherapy:usually2coursesofidarubicinandaraC.MaintenancetherapywithATRA,6-MP,andmethotrexateArsenicTrioxideTreatmentofrelapseandrefractoryAMLHSCTClinicaltrialTreatmentofAgedALReducedosechemotherapyChronicmyelogenousleukaemia

ChronicMyelogenousLeukemia(CML)CML -myeloproliferativedisoder-increasedproliferationofgranulocyticcellsstillhascapacitytodifferentiation

*peripheralbloodshowincreased granulocyticcellswiththeirimmature precursorsEpidemiologyofCML

15%ofleukemiainadultsOccursmainlybetweentheageof30-70yrsCause;stillunknownIncreasedincidencewasreportedinradiationexposureareasuchasbenzene,andchemicals-Survivalforolderformtherapywas3-5yearsChronicphaseClinicalfeatures30percentofpatientareasymptomaticatthetimeofdiagnosisSymptomsaregradualinonset:easyfatigability,malaise,anorexia,abdominaldiscomfort,weightloss,excessivesweatingClinicalfeaturesLessfrequentsymptoms:Nightsweats,heatintolerance-mimickinghyperthyroidism,goutyarthitis,Physicalsigns:Pallor,splenomegaly,sternalpainClinicalfeaturessymptomsofleukostasistinnitus,stuporsplenicinfartion(leftupper-quadrantandleftshoulderpain),urticaria(resultofhistaminerelease)priapismLaboratoryfeaturesBloodTheWBC↑above22000/μl(oftenabove100000/μl),granulocytesatallstagesofdevelopmentThebasophilescountisincreased↑Neutrophilsalkalinephosphatase(NAP)activityisloworabsent(90%)LaboratoryfeaturesTheplateletcountisnormalorincreasedThehemoglobinconcentrationisdecreasedNucleatedredcellsinbloodfilmLaboratoryfeaturesBonemarrow:Themarrowishypercellular(granulocytichyperplasia)ChemistryprofileHyperuricemiaSerumvitaminB12-bindingproteineandserumvitaminB12levelsareincreasedLaboratoryfeaturesCytogenetictest-presenceofthePhchromosomeMoleculartest–presenceoftheBCR-ABLfusiongeneEtiologyofCMLPhiladelphiachromosome,Ph1(>95%)Non-Philadelphiachromosome(<5%)p190p210chimericproteinp239TyrosinekinaseactivityPathogenesis

AcceleratedphaseofCMLMostpatientseventuallybecameresistanttotherapyandthediseaseentersamoreagressivephaserefractorysplenomegalyorrefractoryleucocytosisSymptomsaregradualinonsetagainAcceleratedphaseofCMLCriteriaofacceleratedphaseBlastsinbloodorbonemarrow-10-19%Basophilia≥20%Thrombocytopenia<100G/lThrombocytaemia>1000G/lAdditionalchromosomalaberrationsReticulinfibrosisBlastphase(blastcrisis)ofCMLCriteriaofblastphaseBlasts≥20%Blasts+promylocte

inBonemarrow≥50%Blasts+promylocte

inperipheralblood≥

30%extramedullarytumors

Diagnosis

Clinicalfeatures:splenomegalytheperipheralbloodfilmshowsleucocyteswithmanyimmatureformsMarrowexaminationshowsincreasedcellularity.NAP(-)CytogeneticshowsthepresenceofthePhchromosomeandbcr/ablDifferentialdiagnosisDiseasesofsplenomegalyLeukemoidreactionMyelofibrosisTreatmentofCPEliminateofhyperleukocytosis:

leukapheresishydroxyureahydratedchemotherapyTreatmentofCPMoleculortargetingtreatmentImatinibmesylate(STI571)isthefirstchoiceItactsbyspecificallyinhibitingtheenhancedproteintyrosinekinaseactivityoftheBCR-ABLoncoproteinandthusreversingthepathologicallyperturbedsignaltransduction.Dose:400mg/dcurativeeffect:8yearsEFS81%、OS85%CCyR83%。ThesecondTKI:DasatinibCMLofT3151mutation:Allo-SCTTreatmentofCPHydroxyureaOftenusedinitiallyforwhitecellcountreductionDose:1-6g/dorally;Thedoseshouldbedecreasedto1-2g/dwhentheleukocytecountreaches20000/μlDrugshouldbestoppedifthewhitecountfallsto5000/μlItdoesnotalterlong-termprognosis

TreatmentofCP

(interferon-α，IFN-α)Interferonhasantiviralandanti-proliferativeactions.ItwasuntilrecentlythedrugofchoiceformanagingCMLinthechronicphase.Itrestoresspleensizeandbloodcountstonormalin70-80%ofpatients.Some10-20%ofpatientsachieveamajorcytogeneticremissionsideeffects:

Interferoninitiallycausesflu-likesymptomsOthersideeffectsincludeanorexia,weightloss,depression,alopecia,rashes,neuropathies,autoimmunedisorders,andthrombocytopenia.

TreatmentofCP

(Allo–HSCT)

Allo-HSCTistheonlywaytocureCML5yearsosisabout80%forCMLinchronicphase.Indication:AnewdiagnosisofchildrenandadolescentsThemosthighriskpredictionofdiseaseprogressionpossibilityTKItreatmentfailureorintolerancetothepatients.TreatmentofAdvancedphasedisease

TreatmentofAP:ThefirstorsecondTKIAllo-HSCTTreatmentofBP/BC:TKI+chemotherapyAllo-HSCT程鵬血液內(nèi)科副主任主任醫(yī)師無黨派人士，醫(yī)學(xué)碩士；碩士研究生導(dǎo)師廣西醫(yī)學(xué)會(huì)血液病學(xué)會(huì)秘書廣西醫(yī)師協(xié)會(huì)血液病學(xué)分會(huì)總干事《血栓與止血》雜志專業(yè)期刊編委。研究方向：1、出凝血疾病的診斷和治療2、地中海貧血的血栓前狀態(tài)3、妊娠相關(guān)血小板減少

Hemorrhagicdisease

出血性疾病概述

GuangXiMedicalUniversitychengpeng2015.03.19定義

因止血功能缺陷而引起的以自發(fā)性出血或血管損傷后止血不止為特征的疾病。HemostasisandThrombosisVascular

，Platelets

，Coagulation血管（Vascular）的止血作用內(nèi)膜（intima)外膜(advertitia)中膜(media)血管的結(jié)構(gòu)程鵬血液內(nèi)科學(xué)主任醫(yī)師

無黨派人士，醫(yī)學(xué)碩士；

碩士研究生導(dǎo)師。廣西醫(yī)學(xué)會(huì)血液病學(xué)會(huì)秘書《血栓與止血》雜志專業(yè)期刊編委。研究方向1、血液病出凝血機(jī)制研究2、地中海貧血的血栓前狀態(tài)3、出血性疾病ITP血栓前狀態(tài)CoagulationCoagulationFactors：

FactorsⅠ～ⅤFactorsⅦ～ⅩⅢPK激肽釋放酶原HMWK高分子量激肽原vWF血管性血友病因子凝血因子共14個(gè)，按羅馬字命名的有12個(gè)，尚有高分子量激肽原(HMWK)，激肽釋放酶原(PK)大多數(shù)由肝臟產(chǎn)生正常情況下，所有因子都處于無活性狀態(tài)依賴維生素K的凝血因子因子II（凝血酶原）因子VII（穩(wěn)定因子）因子IX（血漿凝血活酶成分）因子X（Stuare-Prower因子)

凝血過程

兩個(gè)途徑（內(nèi)源性、外源性）三個(gè)階段：一、凝血活酶生成二、凝血酶生成三、纖維蛋白生成內(nèi)源性凝血途徑外源性凝血途徑

負(fù)電荷物質(zhì)ⅫⅫaⅪⅪaⅢⅨⅨaⅦaⅦCa2+ⅢⅧCa2+PF3

ⅩⅩaⅤ凝血活酶Ca2+

磷脂

凝血酶原（Ⅱ）凝血酶（Ⅱa）

ⅠⅠa←ⅩⅢa←－ⅩⅢⅠbCa2+注：PF3血小板第3因子，Ⅰa：不穩(wěn)定纖維蛋白Ⅰb：穩(wěn)定纖維蛋白凝血酶誘導(dǎo)血小板不可逆聚集，加速其活化激活Ⅻ因子，啟動(dòng)內(nèi)源性凝血系統(tǒng)激活ⅩⅢ因子，加速穩(wěn)定纖維蛋白的形成加速凝血酶原激活纖溶酶原纖溶酶纖維蛋白溶解+抗凝與纖維蛋白溶解機(jī)制（一）抗凝系統(tǒng)的組成及作用1、抗凝血酶（ATantithrombin）

主要功能：滅活FⅩa及凝血酶

其他絲氨酸蛋白酶：FⅨa、FⅪa、FⅫa

抗凝與纖維蛋白溶解機(jī)制2、蛋白C系統(tǒng)(proteinC、proteinS、TM)

凝血酶+TM—裂解PC—形成活化PC（APC）—滅活FⅤa、FⅧa抗凝與纖維蛋白溶解機(jī)制3、組織因子途徑抑制物

(tissuefactorpathwayinhibitorTFPI)4、肝素(heparin)抗凝系統(tǒng)的組成和作用FⅫaPC-S（一）AT-Ⅲ

FⅪaFⅨaⅧaFⅩaFⅤaPF3Ca++TFPI+Hyvecinthrombinprothrombin（一）（一）（一）（一）（一）（一）（一）（二）纖維蛋白溶解系統(tǒng)組成與激活1、組成：（1）纖溶酶原（plasminogenPLG）（2）組織型纖溶酶原活化劑（t-PAtissueplasminogenactivator）(3)尿激酶型纖溶酶原活化劑（u-PAurokinaseplasminogenactivator）。