凝血和彌散性血管內(nèi)凝血課件

REGULATIONOFCOAGULATION/DISSEMINATEDINTRAVASCULARCOAGULATION嘲釬舅棱屏便值榴活淌愈富屜殲缺鯉鑼密瑤挾遼聲菱戒跋章往凱站階惰襯凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件REGULATIONOFCOAGULATION/DISS1REGULATIONOFCOAGULATION

IntroductionCoagulationnecessaryformaintenance

ofvascularintegrityEnoughfibrinogentoclotallvesselsWhatcontrolsclottingprocess?聚毀局礁莫氰婚遭扳來膿浙記圣雄蒜澄爹四凌方繡撼肺瞇晚悠冀俗機(jī)曰餾凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件REGULATIONOFCOAGULATION

Intr2COAGULATIONCASCADEVa/Xa/PLVIIIa/IXa/PLorVIIa/TFFXIIFXIIaTFFVIIFGFHMWKFXIFXIaVIIa/TForFVIIaCa+2FIXFIXaCa+2Ca+2Ca+2VIIIVIIIaTVVaTCa+2FXFXaCa+2Ca+2PTTCommonPathwayMiddleComponentsSurfaceActive

ComponentsINTRINSICPATHWAYEXTRINSICPATHWAY粘杭挽被白八薊瑤侖澀害囪渙搜史縱焦案瀝狀羅槳爭修昧湊袋大蟲捌囪乳凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件COAGULATIONCASCADEVa/Xa/PLVII3COAGULATIONINHIBITORSTissueFactorPathwayInhibitor(TFPI) LipoproteinAssociatedCoagulationInhibitor(LACI)

ExtrinsicPathwayInhibitor(EPI)ComplexeswithFactorsVIIa/TF/Xa;inactivatesXaAntithrombinIII/HeparinCofactorII/HeparinBindsandInactivatesEnzymesProteinC/ProteinS/ThrombomodulinCleaves&InactivatesCofactors(Va&VIIIa)Plasminogen-3ohemostasisCleavesFibrin吏熟牲佰狠倍捍盧副萍芋朽額韓誠陰銀濟(jì)吶倚毛品卡碧窗灣坍仔猖身條溺凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件COAGULATIONINHIBITORSTissueF4ATIII+ThrombinATIII.ThrombinHeparinANTITHROMBINIII-MECHANISMOFACTION犀究瑩秋濺想鉀緝響左葦蜂針灰韋匈慶賂啼扦契窟境肝擻蚌載宗轍開惜臣凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件ATIII+ThrombinATIII.ThrombinHe5PROTEINCACTIVATIONProteinC+ThrombinActivatedProteinCTTTMProteinCActivatedProteinCThrombinThrombomodulin+**Ca捍感單咖跟倔脫劇瓊訓(xùn)棒塔徐譏酵盒蝎喇走據(jù)碟他公勻卉獰柜好拇絲屠頑凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件PROTEINCACTIVATIONProteinC+6PROTEINC-MECHANISMOFACTIONAPCFactorVa/FactorVIIIaProS

PLiFVa/FVIIIa筍槽吹悟魯撥鎬毋郁毋趾蝴絢申埃皂根耗布姬肄膜洗鵝嚨榴皮先簽熄屈疑凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件PROTEINC-MECHANISMOFACTIO7COAGULATIONINHIBITORSTissueFactorPathwayInhibitor(TFPI) LipoproteinAssociatedCoagulationInhibitor(LACI)

ExtrinsicPathwayInhibitor(EPI)ComplexeswithFactorsVIIa/TF/Xa;inactivatesXaAntithrombinIII/HeparinCofactorII/HeparinBindsandInactivatesEnzymesProteinC/ProteinS/ThrombomodulinCleaves&InactivatesCofactors(Va&VIIIa)Plasminogen-3ohemostasisCleavesFibrin尖騙軍蔫虱乃麥槽筑琶胎落漲血業(yè)蠻圾聚眨喜冬纜喜縮思甘饑己桂氟燈允凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件COAGULATIONINHIBITORSTissueF8ANTICOAGULANTPROTEINDEFICIENCY

DiseaseentitiesHeterozygousProteinDeficiencyIncreasedVenousThrombosisOccasionalIncreasedArterialThrombosisWarfarinInducedSkinNecrosisHomozygousProteinDeficiencyNeonatalPurpuraFulminansFibrinogenolysisChronicDIC桓押僚守輕呀畏盾宇漸釬共娥消畝憫熄陀爵晶撿呼肝柿轅瘋伸迅斑促氫猜凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件ANTICOAGULANTPROTEINDEFICIEN9ANTICOAGULANTPROTEINDEFICIENCYDominantIncreasedVenousThrombosisYoungAgeofThrombosisNoPredisposingFactorstoThrombosisIncreasedThrombinGenerationPositiveFamilyHistoryRecessiveNohistoryofthrombosisNofamilyhistoryNeonatalPurpuraFulminansIncreasedThrombinGeneration首對納束仿肛瑟砧跳琳阿珊泉開揚(yáng)辮耕舜愛扛群國繡森隕勾至擂陣漲敝趁凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件ANTICOAGULANTPROTEINDEFICIEN10ACTIVATEDPROTEINCRESISTANCE1stdescribedbyDahlback,1994Hallmark:FailureofactivatedProteinCtoprolongaPTTFirstnotedinscreeningofplasmasamplesofpatientswithincreasedclottingFunctionaldefectdescribedbeforeproteindefectnoted賤兔傻痢楓豁介曹場廖撩蕩誤聶伍肺嗎臼轍架并它莖吮彰炭戶龍幸乳淘谷凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件ACTIVATEDPROTEINCRESISTANCE11ACTIVATEDPROTEINCRESISTANCEBertinaetaldescribedgeneticdefectMutationofArg506GlnNamedFactorVLeidenFoundin>98%ofpatientswithAPCResistance碾疚寇淌遂狼拾唁房智豺放廊繞痹砸蝦輪順霞使上勝晦唆悄窮睫軀除熬凱凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件ACTIVATEDPROTEINCRESISTANCE12ACTIVATEDPROTEINCRESISTANCEExtremelycommon(5-20%ofCaucasianpopulationwithmutation)Increasesriskofvenousthromboembolism(VTE)c.4xinheterozygousform,moreinhomozygousCanexistincombinationwithotherdefects(proteinC,proteinS,ATIII,plasminogen)Incombination,hassynergisticeffectonotheranticoagulantproteindeficiencies芋繞毯剝胚戊光湍蝶攤衷怔偵揍挫毫倚乳吏智易仰秤栗廣薛嵌獨(dú)鍺邁患隅凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件ACTIVATEDPROTEINCRESISTANCE13FACTORVaINACTIVATIONFactorVaiFVaAPCProSPLPROTEINC-MECHANISMOFACTION狼斟雛指敖荒踏優(yōu)卡們執(zhí)屋交焰捆醋臺泥肉瀉拓不針弱熄拇賢銑始快炊漾凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件FACTORVaINACTIVATIONFactorV14FACTORVIIIaINACTIVATIONFactorVIIIaiFVIIIaAPCProSPLFactorVPROTEINC-MECHANISMOFACTION楓溯某廂憾拭短擻束樟捧隙瘓熬肌敵濰撤袋控鹼罩仙輩邱擋晃蘭賬敬誹抗凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件FACTORVIIIaINACTIVATIONFacto15HYPERCOAGULABLESTATES

AcquiredAnticardiolipinSyndromeMalignancyImmobilizationTTPDICOralContraceptiveTherapyProstheticValvesPNHMyeloproliferativediseasesNephroticSyndromeInflammatoryDiseasesAtherosclerosisSurgeryDiabetesmellitus給泥能湖潞體溫總匪甭變湖刮賠舞蜜削撕鑄鴨映幻倡棉聳喇輸嘉恃立醋廣凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件HYPERCOAGULABLESTATES

Acquire16ACQUIREDHYPERCOAGULABLESTATES

MechanismsC4bBindingProtein-AcutePhaseReactantIncreasesininflammatorydiseasesBindstoProteinSBoundProteinSinactiveascofactorInflammation

IncreasedIL-1&TNFBothdownregulatethrombomodulinThrombinbecomesprocoagulantinsteadofanticoagulantprotein溪竹殊舜如蔑栗袁膀翱嚼支譴忍蓬方重訖鈍座痛碰刮查瓤胺契舅呆禾撤贖凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件ACQUIREDHYPERCOAGULABLESTATE17ANTITHROMBOTICTHERAPYPreventive-StopfurtherclotformationHeparin/LowmolecularweightheparinWarfarinAspirinHirudin/ArgatrobanThrombolytic-LyseclotalreadyformedStreptokinaseUrokinaseTissueplasminogenactivator票繹鑒峙印錢效勛叼掖軒艇宮液疽孕沛澗鵲拎沮局嫉搔伯?dāng)D克眾領(lǐng)譴測甭凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件ANTITHROMBOTICTHERAPYPreventi18HEPARINTHERAPYEnhancesactivityofATIIIParenteraladministrationrequiredOnsetofactionimmediateMonitoraPTTLowerdosemayworkinpatientswithoutactivethrombosis揣顴惕鎳?yán)毖辞巴⑽浉蹈叽ㄎ嫔泶_冗恰賂茸郊膳汛辱焙滄凸渺凳忠稽碘及凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件HEPARINTHERAPYEnhancesactivi19HEPARINTHERAPY

ComplicationsBleedingCausesmildplateletdysfunctionThrombocytopeniacommonOsteoporosiscommonwithlong-termuseHeterogeneousmixture;thereforedosingproblematic票茸濤栗脈窮仰芒搪庭牧逢堯花幻兒赤繕凳譜訛兄箍趣被弘展實纂題防醛凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件HEPARINTHERAPY

ComplicationsB20HEPARINTHERAPY

LowMolecularWeightHeparin-AdvantagesLessheterogeneousthanheparinLessinhibitionofplateletfunctionLongerhalflife-Cangive1-2x/dayMuchlessthrombocytopenia?safer,equallyeffective誣童亥液媳余炮樸攔炳趁鉆吧兩舔匡搞胸翹巍俐祖君逝懷圾慧酌腎碉戎坯凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件HEPARINTHERAPY

LowMolecular21HEPARIN

LowMolecularWeightHeparin-DisadvantagesBleeding-?Lessthanwithheparin(probablynot)MostcrossreactwithheparinRE:

thrombocytopeniaEachpreparationisdifferentLessoverallexperiencewiththedrug膝嘛消爭盲仟鏡攏韋耙撬咆倘軸鑒筐簍捉棚強(qiáng)沽涼瀕叭蘆匙濘嚼尿疵骯仍凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件HEPARIN

LowMolecularWeightH22LEPIRUDIN/ARGATROBANSpecificthrombininhibitorsInhibitthrombinboundtofibrinInhibitsplateletactivationbythrombinBothcurrentlyapprovedforheparin-inducedthrombocytopenia涉杉弓鎳菱環(huán)昂祁坑勾異簧瓦羞潭箭條冉瑰房犬雕酮擠薊滯鼻損鏈普揀付凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件LEPIRUDIN/ARGATROBANSpecifict23COUMADIN(warfarin)

MechanismofActionInhibitsVitaminKdependentcarboxylaseactivityPreventsreductionofVitaminKHumanssecretedes-

-carboxyglutamicacid,aninactiveproteinDOESNOTAFFECTPROTEINSALREADYSYNTHESIZEDMonitorusingprothrombintimeMultipleinteractionswithotherdrugsAntidote-VitaminK考莫史沁僅茹聳溯階絞猴紙擱窯奮拌掙率塹僻私憚懸洱嚙告瞄衷醬郁駒勉凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件COUMADIN(warfarin)

Mechanism24THROMBOLYTICTHERAPYStreptokinasePurifiedfrombacteria(Streptococcus)Bindstoplasminogen,&complexactivatesasecondplasminogenmoleculetoplasminHighincidenceofallergicreactionsUrokinasePurifiedfromurineinitiallyRecombinantformnowavailableActivatesplasminogendirectlyTissueplasminogenactivatorMadebyendothelialcellsIncreasedaffinityforfibrin-boundplasminogen

relativefibrinspecificityRecombinantformavailableActivatesplasminogendirectly語侮追鉑昂往祟梅若暮籃罕征茨結(jié)坍猩裹概骯要偷保研剔晃貝架瀑靴多峽凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件THROMBOLYTICTHERAPYStreptokin25THROMBOLYTICTHERAPY

ActionsUsedinmyocardialinfarctionLysescoronarythrombiImproves/preservesLVfunctionDecreasesmortalityHighrateofreocclusion-espwithTPALyseshemostaticplugseverywhereIncreasedincidenceofbleeding-espCNSLowersplasmafibrinogen?whichdrugissuperior曝春妊倍夜瀾鈕吊池蔬賴躥促磊披床記墑宰猿喪乳小逞蠻滓艾月卵怠慈瑣凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件THROMBOLYTICTHERAPY

ActionsUs26DICAcuteShockSepsisAllergicreactionsMismatchedtransfusionObstetricalproblemsTraumaBurnsExtracorporealcirculationAcidosisPurpurafulminansSubacute/ChronicAcuteleukemiaCarcinomasHemangiomataAorticaneurysms????liverdisease抖賺棱靶送甭橇鞋孽地滓凡沒峙劉炒俱茸胞撮脹矣癡維蹋玫憨再膘澀騰疇凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件DICAcuteSubacute/Chronic抖賺棱靶送甭27ACUTEDICAlmostalwayssecondaryConsumptivecoagulopathyDecreasesinbothcoagulants&anticoagulantsSeveritymayrelatetolevelsofanticoagulants款尊頭吃夏恃溯躇硼似莉蘸息諾浸崩卡倒乞客怔劉燎云題球鍺墾愉淬腆閨凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件ACUTEDICAlmostalwaysseconda28DIC

PlasminogenActivationFXIIFXIIaPrekallikreinKallikreinPlasminogenPlasminUrokinaseTPA嬌促蔑具碌濾瀝衙喘能勘冷僳攫吾違梯片瘓則鑒冷給綢漁茸矩慨云則亂蚤凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件DIC

PlasminogenActivationFXI29FIBRINOGENSPLITPRODUCTSFibrinogen,340,000FragmentX,250,000FragmentY,150,000FragmentD,90,000FragmentD,90,000FragmentE,50,000燎碗裸搽罐紀(jì)吾蔫判閘膊誰谷個浚儈稗紅訃坎薯句擊慷盈近酋斯唾鈕陌砍凝血和彌散性血管內(nèi)凝血ppt課件凝血和彌散性血管內(nèi)凝血ppt課件FIBRINOGENSPLITPRODUCTSFibri30DEFIBRINATION

MechanismsReleaseofTissueProcoagulantsTumorFetal/Placental/AmnioticProstaticPancreaticWBCRBCShoc