弥散性血管内凝血0 课件

DisseminatedIntravascularCoagulation弥散性血管内凝血DisseminatedIntravascularCoa1Whatdidthebabyoccur?DengueHemorrhagicFeverWhatdidthebabyoccur?Dengue2OutlineofChapterWhatisDIC?HowandwhydoesDICoccur?(etiologyandpathogenesis)WhichfactorscaninfluencethedevelopmentofDICManifestationofclinicPrincipleofpreventionandtreatmentOverviewofhemostaticsystemOutlineofChapterWhatisDIC?31.OverviewofhaemostaticprocessComponentofhemostasisKeepfluidity,capacityofcoagulation

Components:vesselwall,platelets,coagulationfactors,Anti-coagulationandFibrinolyticfactors.

Anti-Coagulationfactors:CellularsystemandsolublesystemFibrinolyticsystem:Plasminogen,plasminandtheirregulatorCoagulationsystem:12ExceptforTFandCa2+

otherssynthesizedbyliver1.Overviewofhaemostaticpro4Whydoesvasospasmoccur?Whataremechanismsofvasospasm?VasospasmofinjuredvesselPlateletsadheretoaninjuredbloodvesselandreleasechemicalfactorsthatcauseformationofplateletplugandcontributetoactivationofacoagulationcascadeLeadtoamountofthrombinFibrinthrombusPlasminogenactivatorsPlasminogenPlasminFibrindisgested,bloodflowrestoredTwocounteractingphasesofhemostasis:bloodcoagulationandfibrinolysisWhydoesvasospasmoccur?What5(1)Extrinsicpathway(Tissuefactorpathway)

(2)Intrinsicpathway(3)Formationofplateletplug

Plateletactivation

Collagen,thrombin,ADP,TXA2,epinephrine,serotonin,argininevasopressinetc..Plateletadhesion

changefromsmoothdiskstospinyspheresandexposingreceptoronitssurface.GPⅠbbindingvWFmediatingplateletsadhesionPlateletaggregationGPⅡb/ⅢamultivalentbindingfibrinPlateletsecretion

ADP,TXA2areimportantforaggregationofplatelet.Interlinkedandpromotedeachother(1)Extrinsicpathway(Tissue6ExtrinsicIntrinsicStableFibrinclotExtrinsicIntrinsicStableFibr7Granule-

ADP,TXA2,SerotoninetcGranule-

Fibrinogen,factorsⅤ,Ⅷ,TGF-

Granule-ADP,TXA2,Serotonin8AnticoagulationSystem

1)Monocyte-macrophagesystem：cleaningouttheclottingfactorssuchastissuefactor,prothrombinaseandfibrinmonomers

2)Solublesystem:

（1）AntithrombinIII(ATIII)、heparin

VIIa,

Ⅸa,Ⅺa,Xa,thrombin

(2)Tissuefactorpathwayinhibitor(TFPI)Xa-TFPI-VIIa-TFTissuefactorPathwayinhibitor:MainproducedbyVascularECsAnticoagulationSystem1)Mono9（3）ProteinCsystemProteinC(PC)、ProteinSandthrombomodulin（TM）Pathwayofanti-coagulation：InhibitⅤa、Ⅷa(2)BlockFⅩacombinedwithplatelet(3)IncreasefibrinolysisPAI-1PAProteinCsystemPCPS-cofactorTM(thrombomodulin)+thrombinactivate（3）ProteinCsystemProteinC10fibrinolyticsystem

PlasminogenPLgPlasminPLnPlasminActivatorExtrinsic:PA,t-PA,u-PA;Intrinsic:thrombin,Ⅺa,Ⅻa,andkallikreinExogenous:Streptokinase,Staphylokinaseplasminogen-activatorinhibitor1(PAI)α2-antiplasminandα2-macroglobulin.Thrombinactivatablefibrinlysisinhibitor(TAFI)

Roleofendothelialcells

fibrinolyticsystemPlasminoge11ATⅢ/HeparinsTFPITM/ThrombinPCAPCAPC/PSMechanismofcoagulationandanticoagulationATⅢ/HeparinsTFPITM/ThrombinPCA12弥散性血管内凝血0课件13DefinitionofDICEtiologicalfactorWidespreadintravascularactivationofcoagulationIntravascularthrombus(fibrin)formation.

Bleeding,Anemia,Shock,OrgandysfunctionDefinitionofDICEtiologicalf14

TypeDiseasesInfectionDiseaseGram-negativeorGram-positivesepsis,viralhemorrhagicfever,viralhepatitisMalignancySolidtumors,acuteleukemiaObstetricconditionsPreeclampsia,placentalabruption,amnioticfluidembolism,caesareanbirth,abortion,TraumaPhysicalforce,burns,braintrauma,surgicaloperationsSevereallergic/toxicreactionsSnakebiteSevereimmunologicreactionsTransfusionreaction

DisordersassociatedwithDIC

Disordersassociatedw15Pathogenesis

ThetissuefactorandsystemicactivationofcoagulationTF-VIIacomplexTheextrinsicpathwaybeactivated(2)

Endothelialinjuryandimbalanceofprocoagulationandanticoagulationanoxia,severeinfectionsandendotoxinEndotheliallesionTForTNFa,IL-1,IL-6PathogenesisThetissuefactor16①DegradationofTM/PCandHS/AT-IIIsystem②Down-regulationoftissuefactorpathwayinhibitor(TFPI)③t-PAreleasedecrease④PAI-1

releaseincrease⑤NO,PGI2andADPenzyme

plateletadherenceandaggregation

(-)collagenexposure(+)intrinsicpathway(+)HK①DegradationofTM/PCandHS/17(4)Bloodcellsdamage(3)Entranceofprocoagulantsubstancestobloodsnakevenom,cancer,pancreas

proteaseRedbloodcell(RBC)damage

ADPactivateplateletphospholipidofcellmembrane2)Whitebloodcells(WBC)damageandactivation

TF-pathway,TNFIL-1,IL-6Anti-coagulationProcoagulation(4)Bloodcellsdamage(3)Entr18弥散性血管内凝血0课件19FactorsinfluencethedevelopmentofDIC

(1)Mononuclearphagocytesystemdysfunction(2)Liverdysfunction(3)Hypercoagulablestate

(4)MicrocirculationdysfunctionFactorsinfluencethedevelopm20solubletissuefactor,endotoxin,thrombinsolublecomplexesoffibrinmonomersEndotoxinlowdoseShwartzmanreaction24hSecondinjectionDICMononuclearphagocytecleansolubletissuefactor,endoto21ClearingactivatedfactorsIX,XandXIReplenishcoagulationfactors,plasminogen,α2-antiplasmin,ATIIIandPCDICClearingactivatedfactorsIX,22Coagulationfactors(I,II,V,VII,IX,X,XII)ATIII,t-PA,u-PAPlacentalabruptionandAmnioticfluidembolismPlacentaltissue:PAIandThromboplastin(TF)DICCoagulationfactors(I,II,V,23accumulationofprocoagulantsandincreasessusceptibilitytoplateletadherenceandaggregation.

acidosis

tissueanoxiaandendotheliallesion

Gianthemangioma(巨型血管瘤)SusceptibilitytoDICaccumulationofprocoagulants24ClinicalclassificationofDIC

ClinicalclassificationofDIC25AcuteDIC:Severalhoursor1-2daysSevereInfection(septicshock),TraumaticShock,IncompatibleBloodTransfusionetc.(2)SubacuteDIC:Overaperiodofsomedays.Malignacies,RetainedDeadFetusSyndromeetc.(3)ChronicDIC:Developandpersistovermanyweeksormonthsanderuptintohemorrhagicorthromboembolicepisode

malignancy,LiverDiseases,ConnectiveTissueDisordersGlomerulonephritis,LupusNephritisandProliferativehemangiomaetc.AcuteDIC:Severalhoursor126StageofDICDepletedHypocoagulablestageCharacteristic:thrombinandcoagulantsdcrease;fibrinolyticsystemactivationbloodpresenthypocoagulablebleedingHypercoagulablestageCharacteristic:morethrombin,microthrombusandbloodpresenthyper-coagulablestatusSecondaryfibrinolyticstageCharacteristic:moreplasminandanticoagulationincreaseandpresentobviousbleedingStageofDICDepletedHypocoagu27Alterationsofmetabolismandfunction

(1)Bleeding(2)Organdysfunction(3)Shock(4)HaemolyticanemiasAlterationsofmetabolismand28Mechanismsofbleeding1)ConsumptionofcoagulationfactorsandplateletsPlasminFXFY+FDFD+FEFDPFbn(Fbg)3)Formationoffibrindegradationproducts(FDP)2)Activationofthefibrinolyticsystem

Mechanismsofbleeding1)Consu29FDPanti-coagulation：1.Blockfibrinmonomercross-linkedcoagulation(X,Y,D)2.Inhibittheformationandactionofthrombin(Y,E)3.InhibitaccumulationofplateletFDPtest：3Ptest(plasmaprotaminparacoagulationtest)D-dimer：IndexofDICHowtodetecthyperfibrinolysisinclinic?FDPanti-coagulation：1.Block30(Plasmaprotaminparacoagulationtest)fibrinogenthrombinFibrin(M)fibrinplasminFX+FY+FD+FEFX.M(solublecomplex