醫(yī)學(xué)DIC彌散性血管內(nèi)凝血課件

Chapter12ChengYangCoagulationandAnti-coagulationImbalanceChapter12ChengYangCoagulatioIntroductionvasospasm血管痙攣thrombosis血小板血栓形成fibrinclotformation纖維蛋白凝塊形成anticoagulationsystemfibrinolyticsystemcoagulationsystem抗凝凝血纖溶hemostasis(止血)Introductionvasospasm血管痙攣throm(I)Coagulationsubstances:platelets&coagulationfactors

Coagulationfactors ProductionsourceFactorI(fibrinogen)LiverFactorII(prothrombin) LiverFactorIII(tissuefactor)TissueFactorIV(Ca2+)FactorVLiverFactorⅥ(obsolete=factorVa)FactorVIILiverFactorVIIIEndothelialcellsFactorIXLiverFactorXLiverFactorXILiverFactorXIILiverFactorXIIIPlatelets I.CoagulationSystemandItsFunction(I)Coagulationsubstances:pla粘附（adhesion）:VECinjury→collagenexpose內(nèi)皮下膠原暴露combinationofpltandcollagenactivatedcollagen，thrombin，ADP,TXA2,platelets粘附（adhesion）:VECinjury→collag聚集（aggregation）:——combinationbetweenpltrest→noaggregationstimuli→aggregation→extendpseudopods（偽足），degranulation（血小板脫顆粒）聚集（aggregation）:——combinationScanningelectronmicrographofmoderatelyactiveplateletPseudopodsScanningelectronmicrographothrombosisplateletadhesionplateletaggregationthrombosisplatel

(II)Coagulationpathways:

1.Extrinsiccoagulationpathway

maincoagulationpathwayinitialstimulusinthiscascadeistissue-basedtissuefactor(TF,factorIII):alipid-richproteinmaterial

Initialfactor:FIII(tissuefactor,TF)tissuefactor+phospholipid+Ca2++factorVIIcanactivatefactorsIXandX.FXathenactivateFII(prothrombin)FIIa(thrombin)cleavesfibrinogen(I)tofibrin(Ia)(II)Coagulationpathways:ExtrinsicPathwayforBloodClottingTissuefactorⅩProthrombinactivatorprothrombinthrombinⅦaⅦⅩaCa2+TissuedamageCa2+Phospholipid(platelet)ⅤaCa2+fibrinogenfibrinⅧaⅤⅧExtrinsicPathwayforBloodCl2.IntrinsiccoagulationpathwayFXII:aprotease(intrinsictotheblood)Initialfactor:FXIIconvertsFXItoFXIaconvertsFIXtoFIXa“phospholipids+Ca2++FXa+FVa”complex(prothrombinactivator)convertsprothrombintothrombincleavesfibrinogenintofibrin2.IntrinsiccoagulationpathwaphospholipidIntrinsicPathwayforBloodClottingfibrinⅩaⅩⅫaⅫⅪaⅪⅨaⅨCa2+ⅧaⅧCa2+prothrombinthrombinProthrombinactivatorⅤⅤaCa2+VECinjuryCa2+fibrinogenplateletphospholipidIntrinsicPathway1.FX→FXa

prothrombinactivatorformation凝血酶原激活物的形成2.prothrombin（FII,凝血酶原）→thrombin(FIIa,凝血酶）3.fibrinogen(Fbg,FI,纖維蛋白原)→fibrin(Fbn,FIa,纖維蛋白)threestagesforcoagulation:1.FX→FXathreestagesforcoag1.Humoralanticoagulationsystem:AnticoagulantfactorsProductionsourceTFPIendothelialcellHeparinLiverAntithrombinIII(AT-III)LiverProteinC(PC)LiverProteinS(PS)LiverPlasminogen LiverFDPIII.AnticoagulationSystem1.HumoralanticoagulationsystheparinTFPI+FⅩa-TFPIcomplexFⅩa-TFPI-FⅦa-TFcomplexTissueFactorPathwayInhibitor(TFPI,組織因子途徑抑制物)Ca2+,XaⅦ,XinactivationVECTFPIheparinTFPI+FⅩa-TFPIcomplexFⅩVEC(內(nèi)皮細(xì)胞)PCAPCFⅤa，F(xiàn)ⅧainactivationPS＋＋血栓調(diào)節(jié)蛋白TMthrombin凝血酶TM-ProteinCSystem（血栓調(diào)節(jié)蛋白-蛋白C系統(tǒng)）thrombinprothrombin凝血酶原VEC(內(nèi)皮細(xì)胞)PCAPCFⅤa，F(xiàn)ⅧaPS＋＋血栓調(diào)節(jié)蛋AntithrombinⅢ&Heparin（抗凝血酶III，肝素）ClearthrombinAT-ⅢclearIIa，VIIa,IXaXIa,Xa,XIIaAT-ⅢheparinX100AntithrombinⅢ&Heparin（抗凝血酶I2.Cellularanticoagulationsystem

monocyte-macrophagesystem&hepatocytecanclearandremoveprocoagulants(endotoxin,Ag-Abcomplex,etc)activatedcoagulationfactors（TF）prothrombinactivatormonomeroffibrincanactivateendogenousanticoagulationsubstancesfibrinolyticsystem2.Cellularanticoagulationsys

Function

dissolvingthethrombusthathasalreadyformedinvessels

使纖維蛋白凝塊溶解,保證血流通暢,也參與組織的修復(fù)和血管的再生等III.FibrinolyticSystemVECandtissueinjuryplasminplasminogenfibrinogenFDPTPA(tissueplasminogenactivator)ⅫaProcess1.Humoralplasminogenactivators：XIIa→plasmaproactivator2.Tissueplasminogenactivators(TPA)：

anoxia，stasis，tissuedamage，andfibrindeposition→VECandtissueinjuryurokinaseandstreptokinase：artificialplasminogenactivatorsFunctionIII.FibrinolyticSyssolublecanhydrolyzefibrinogenandmanycoagulationfactorsanticoagulationeffect

fibrindegradationproducts,FDP，纖維蛋白降解產(chǎn)物solublefibrindegradationprodDisseminatedIntravascularCoagulation,DICDisseminatedIntravascularCoaI.ConceptofDIC

DICisapathologicalsyndromecharacterizedbybleeding,Bp↓orshock,multipleorgandysfunction(embolism)andanemia,whichresultsfromthedisturbanceofkineticbalanceofcoagulationandfibrinolyticprocesses(hypercoagulable→hypocoagulable).causes→extensiveactivationofclottingfactors(hypercoagulablestate)→↑c(diǎn)onsumptionofclottingfactorsandplatelet,depositionoffibrinandsecondaryfibrinolysis(hypocoagulablestate)→bleeding,Bp↓orshock,multipleorgandysfunction(embolism),anemiaI.ConceptofDICDICi[醫(yī)學(xué)]DIC彌散性血管內(nèi)凝血課件[醫(yī)學(xué)]DIC彌散性血管內(nèi)凝血課件Waterhouse-FriderichsensyndromeadrenalnecrosisWaterhouse-FriderichsensyndroMeningococcemia(腦膜炎球菌血癥)onthecalves(小腿）Meningococcemia(腦膜炎球菌血癥)onthMeningococcemiaassociatedpurpuraMeningococcemiaassociatedpur(I)Etiology1.Infection(mostcommon):

bacteriaandtheirtoxins,fungi,viruses,rickettsiae;tuberculosis,abscesses,osteomyelitis

2.Malignancy:

acutepromyelocyticleukemia,acutemonocyticleukemia,disseminatedprostaticcarcinoma;lung,breast,gastrointestinalmalignancy

3.Obstetricalcomplications:

abruptionplacenta,abortions,amnioticfluidembolism,hemorrhagicshock;deadfetussyndrome

4.Trauma&largeoperation:

massivetissuedestruction,braindamage,massiveburn,organtransplantation5.Vasculardisease:

braininfarctionorhemorrhage;aorticaneurysm,gianthemangioma

6.Others:

heparin-inducedthrombocytopeniawiththrombosis(HITT)purpurainnewborns(homozygousproteinCdeficiency)II.EtiologyandPathogenesisofDIC(I)Etiology1.Infection(most[醫(yī)學(xué)]DIC彌散性血管內(nèi)凝血課件

TFreleaseandactivationofextrinsiccoagulationtrauma，burn，largeoperation(12.7-15%)，obstetriccomplications(8.6-20%)malignanttissuenecrosis(20-28.3%),leukemiacellinjury(II)Pathogenesis→FIII(tissuefactor)releaseintoblood→extrinsiccoagulation(+)TFreleaseandactivationofsiteactivityofTF(μ/mg)

liver10

muscle20

brain50

lung50placenta2000Q：為什么產(chǎn)婦容易發(fā)生DIC？siteactivactivateFⅫ→intrinsiccoagulation(+)VECinjury→releaseTF→extrinsiccoagulation(+)anticoagulanteffect↓NO、PGI2、ADPaseproduction↓→↓inhibitioneffectofPLTadhesionandaggregationvascularendothelialcellsdamageandcoagulationandanticoagulationimbalancesevereinfectionandendotoxemia;severeacidosis;persistenttissueischemiaandhypoxia;strongimmunereactions→Ag-AbcomplexCauses:Mechanism:activateFⅫ→intrinsiccoagulexcessivedestructionofbloodcellsandactivationofplateletssevereRBCdestruction:transfusionofincompatiableblood,acutehemolyticreactions→RBCinjury→*absorbVII,IX,Xandprothrombintoacceleratecoagulation*releaseofADPandPF3→initiateaplateletreleasereaction→adhesion&aggregationofplateletexcessivedestructionofb[醫(yī)學(xué)]DIC彌散性血管內(nèi)凝血課件

WBCdestruction:acutepromyelocyticleukemia,chemotherapytreatment→WBCinjury→aTF-likeagentrelease→extrinsiccoagulationtriggeredbacterialsepsis→endotoxin,IL-1,TNF-αrelease→extrinsiccoagulationtriggeredWBCdestruction:Destructionoractivationofplatelets:

endotoxin,antigen-antibodycomplex→damageplatelets→releaseofPF3,PF4,β-TGPF3:canacceleratetheactivationofprothrombinPF4:canneutralizetheactionofheparinβ-TG:canpromotethecoagulationofbloodDestructionoractivationofpacutenecroticpancreatitis→releaseoftrypsin(enzyme)→convertingprothrombintothrombinsnakevenom→activationofFX,FV,prothrombin;conversionoffibrinogentofibrinmetastaticcancercells→secreteprocoagulantsubstancesamnioticfluidembolism→TF-likeagentreleasetrauma,burns,viruses→activationofFX→coagulationsystem(+)Ag-Abcomplex→activationofFXII→coagulationsystem(+)bacteria(endotoxins)→activationofTF

Pro-coagulantsenteringcirculationacutenecroticpancreatitis→ExcessiveclottingInfectionCancerChildbirth,deadfetus,orsurgerySevereheadinjuryPoisonoussnakeClottingfactorsandplateletsaredepletedExcessivebleedingoccursEndothelialdamage;tissuedamage;directoractivationoffactorX,damageofbloodcellsHypercoagulablestageHypocoagulablestageSecondaryfibrinolyticstageExcessiveclottingInfectionCan

Inappropriatelyconditionedmonocyte-macrophagessystemIII.PrecipitatingFactorsofDICmonocyte-macrophagesystem:

macrophagesinspleenandtheKupffercellsinliver

Function:removeseveralprocoagulantsubstances(thrombin,fibrin,etc.)removeplasmin,FDP,endotoxin,etc.Necrotictissueandbacteriacanblockitsfunction.InappropriatelyconditionedmExperimentalstudy:

GeneralShwartzmanreaction(GSR,全身性S反應(yīng)):

GSRisaDIC-shocksyndromeaftertwotemporallyspacedintravenousinjectionofsmalldoseofbacterialendotoxins.Theinjectionsofendotoxinscanblockthereticuloendothelialsystem,whichcaninduceDIC.

the1sttime:consumptionofmonocyte-macrophagesystem

the2ndtime:blockadeofmonocyte-macrophagesystem,↓deactivationofendotoxins→bloodcoagultionExperimentalstudy:Liver:clearFIXa,FXa,FXIa,etc.synthesizePC,AT-III,plasminogen,etc.Severehepaticdysfunction↓synthesisofPC,AT-III,plasminogen,etc.inactivationofclottingfactorsdisturbanceshepatocytesnecrosis→TFreleaseLiver:SeverehepaticdysfunctiPregnancy:from3ndweekpregnancy→PLT,FVII,XII,X,IX,V,II,I,etc↑↑AT-III↓Plasminogenactivatorinhibitor(PAI)↑Fibrinolyticactivity↓→bloodcoagulation

mostmarkedintheterminalstageofpregnancyHypercoagulablestatusPregnancy:from3ndweekHyperAcidosis:acidosis→damageVEC→intrinsiccoagulation(+)pH↓→plateletactivity↑→↑aggregationandadhesionofplateletactivityofheparin↓activityofclottingfactors↑→bloodcoagulationAcidosis:shock→bloodflowstasis,aggregationofbloodcells

appearanceofsludgingVasculardisorders:hugeaorticaneurysms,gianthemangiomas（巨大血管瘤）→bloodflowslowdown→

localactivationofcoagulationcascadebleedingtendency→consumptionofplateletandfibrinogenbloodvolume↓→hepaticanticoagulationeffect↓,fibrinolysiseffectdisturbancesMicrocirculationdisordershock→bloodflowstasis,aggresmokingdiabetesintheterminalstageofpregnancysomedrugs(fibrinolyticinhibitors)DecreasedfibrinolyticactivitysmokingDecreasedfibrinolyticIV.StagesofDICstagesbloodclinicalmanifestationshypercoagulablestageclottingfactors↑,PLT↑,productionofmicrothrombiembolismconsumptivehypocoagulablestageplateletandclottingfactorsconsumption↑；firinolyticactivationbleeding,shocksecondaryfibrinolyticstagefibrinolyticactivity↑↑plasminformationFDPformationobviousbleedingIV.StagesofDICstagesbloodcl

Accordingtoclinicalcourse:1.AcuteDIC:developsrapidlyoverseveralhoursorl-2daysunderlyingdiseases:septicemia,shock,severetrauma,etc.2.SubacuteDIC:developsoveraperiodofseveraldaysunderlyingdiseases:malignancies,intrauterinefetaldead,gianthemangiomas,etc.3.ChronicDIC:developsandpersistsovermanyweeksormonthsunderlyingdiseases:malignancy,1iverandkidneydisease,etc.V.ClinicalClassificationofDICAccordingtoclinical

Accordingtocompensatorylevel:

decompensatedcompensatedovercompensated

clotting

consumptionconsumptionconsumptionfactors>production=production<productionDIClevelacute,severeslightchronic,recoverysymptomstypicalnotobviousnottypicallaboratoryclottingfactors↓noobviouschangesclottingfactors↑findingsAccordingtocompensa

DecompensatedDICCompensatedDIC OvercompensatedDIC AcuteDIC Subacute／ChronicDIC ChronicDICClinicaloverseveralhoursaboutoveraperiodofaboutovermanyweekscourseor1-2daysseveraldaystomonthsDepletionvs repletionofDepletion>repletionDepletion=repletionDepletion<repletionclotFactors/PLs

Laboratory↓Clotfactors↑Clotfactors↑Clotfactorsfeatures ↓PLs↑PLs↑PLsClinicalBleeding(+++)Bleeding(+or±)Bleeding(+or±)featuresShock(+++)Shock(-)Shock(-)Thrombo-Emboli(+)Thrombo-emboli(±) Thrombo-emboli(±)CausesSevereviralorbacteriaMalignanciesMalignancyinfectionsIntrauterinefetaldeadLiverandkidneydiseaseTraumaGianthemangiomasIncompatiblebloodtransfusionDecompen

(I)Bleeding(II)Organdysfunction(III)Shock(IV)MicroangiopathichemolyticanemiaVI.Function&MetabolicChangeofDICVI.Function&MetabolicChan

(I)Bleeding:84-88%petechia（皮膚瘀斑）purpura（紫癜）hematemesis（嘔血）melena（黑便）hemoptysis（咯血）hematuria（血尿）rhinorrhagia（鼻出血）colporrhagia（vaginalbleeding,陰道出血）(I)Bleeding:84-88%petechia（腹主動(dòng)脈瘤（abdominalaorticaneurysm）腹主動(dòng)脈瘤（abdominalaorticaneurysMechanismofBleeding:

1.consumptionofcoagulationfactors2.secondaryfibrinolysis3.formationoffibrindegradationproducts(FDPs)(1)inhibitionofplateletaggregation(2)inhibitpolymerizationoffibrinmonomerMechanismofBleeding:(II)

Organdysfunction:“embolism”→MODSevenMOF

lungs,kidneys,brain,heart,liver,spleen,pancreas,GItract,skin,etcrespiratoryfailure——ARDSrenalfailureheartfailurehepaticfailure(II)Organdysfunction:resrenalfailure—renalcortexnecrosisWaterhouse-FriderichsenSyndrome——acuteadrenalfailureSheehan’sSyndrome——pituitarynecrosisrenalfailure—renalcortexne

microthrombiinmyocardiummicrothrombiinlivermicrothrombiinmyocardiummicrothrombiinkidneymicrothrombiinlungmicrothrombiinkidneym(III)Shock↑bloodreturnheart↓peripheralresistance↓vasodilation,capillarypermeability↑histamine,bradykininkinin,complement,fibrinolyticsystem(+)C.O.↓myocardialcontractility↓microthrombiinheartbloodcoagulation↑ECBV↓continuousbleedingconsumptionofclottingfactorsandplateletclottingfactors(+)(III)Shock↑bloodreturn↓peri

(IV)Microangiopathichemolytic

anemia

Theredbloodcellsappearfragmented.Twistedcells,crenatedcells,triangularcells,helmet-shapedcells,andmicrospherocytesareseenonthebloodsmear.Theseabnormalcellsarecalledschistocytes.(IV)Microangiopathichemolyt[醫(yī)學(xué)]DIC彌散性血管內(nèi)凝血課件Mechanismforschistocyte:TheschistocytesresultfromphysicaldamagetotheRBCscausedbytheirpassageamongthelotsofstrandsornetsoffibrin.Mechanismforschistocyte:[醫(yī)學(xué)]DIC彌散性血管內(nèi)凝血課件[醫(yī)學(xué)]DIC彌散性血管內(nèi)凝血課件[醫(yī)學(xué)]DIC彌散性血管內(nèi)凝血課件VII.PathophysiologicalbasisofpreventionandtreatmentofDIC

1.ReversingtheunderlyingdisordersinitiatingDIC:“Treatmentofcausativediseases”septicemia———————————usingantibioticsmalignancies——————————chemotherapyintrauterinefetaldead——————removalofdeadfetustreatmentofshock2.Improvingthemicrocirculation:

Transfusion:increasingtheblood-flowsuitably

Smalldoseofaspirin:inhibitaggregationandadhesionofplatelet

Thrombolysis:streptokinase&urokinase(“plasminogenactivators”)VII.Pathophysiologicalbasis3.Reconstructingthebalanceamongcoagulation,anticoagulationandfibrinolysis:(1)Anticoagulationtherapy:high-doseheparinand/orAT-IIIreplacementtherapyinhypercoagulablestage*administrationofheparinmayleadtoanincreaseinbleeding*(2)Bloodtransfusion:Clottingfactorsreplacement:withfresh,frozenplasma,freshw