凝血和弥散性血管内凝血讲座

烦恼有何惧怕，既然躲不掉，就调好心态与它共存。心向阳光，何惧风霜。

茫茫人海你我相遇就是缘分，欢迎下载！2021/8/121REGULATIONOFCOAGULATION/DISSEMINATEDINTRAVASCULARCOAGULATION2021/8/122REGULATIONOFCOAGULATION

IntroductionCoagulationnecessaryformaintenance

ofvascularintegrityEnoughfibrinogentoclotallvesselsWhatcontrolsclottingprocess?2021/8/123COAGULATIONCASCADEVa/Xa/PLVIIIa/IXa/PLorVIIa/TFFXIIFXIIaTFFVIIFGFHMWKFXIFXIaVIIa/TForFVIIaCa+2FIXFIXaCa+2Ca+2Ca+2VIIIVIIIaTVVaTCa+2FXFXaCa+2Ca+2PTTCommonPathwayMiddleComponentsSurfaceActive

ComponentsINTRINSICPATHWAYEXTRINSICPATHWAY2021/8/124COAGULATIONINHIBITORSTissueFactorPathwayInhibitor(TFPI) LipoproteinAssociatedCoagulationInhibitor(LACI)

ExtrinsicPathwayInhibitor(EPI)ComplexeswithFactorsVIIa/TF/Xa;inactivatesXaAntithrombinIII/HeparinCofactorII/HeparinBindsandInactivatesEnzymesProteinC/ProteinS/ThrombomodulinCleaves&InactivatesCofactors(Va&VIIIa)Plasminogen-3ºhemostasisCleavesFibrin2021/8/125ATIII+ThrombinATIII.ThrombinHeparinANTITHROMBINIII-MECHANISMOFACTION2021/8/126PROTEINCACTIVATIONProteinC+ThrombinActivatedProteinCTTTMProteinCActivatedProteinCThrombinThrombomodulin+**Ca2021/8/127PROTEINC-MECHANISMOFACTIONAPCFactorVa/FactorVIIIaProS

PLiFVa/FVIIIa2021/8/128COAGULATIONINHIBITORSTissueFactorPathwayInhibitor(TFPI) LipoproteinAssociatedCoagulationInhibitor(LACI)

ExtrinsicPathwayInhibitor(EPI)ComplexeswithFactorsVIIa/TF/Xa;inactivatesXaAntithrombinIII/HeparinCofactorII/HeparinBindsandInactivatesEnzymesProteinC/ProteinS/ThrombomodulinCleaves&InactivatesCofactors(Va&VIIIa)Plasminogen-3ºhemostasisCleavesFibrin2021/8/129ANTICOAGULANTPROTEINDEFICIENCY

Diseaseentities

HeterozygousProteinDeficiencyIncreasedVenousThrombosisOccasionalIncreasedArterialThrombosisWarfarinInducedSkinNecrosisHomozygousProteinDeficiencyNeonatalPurpuraFulminansFibrinogenolysisChronicDIC2021/8/1210ANTICOAGULANTPROTEINDEFICIENCYDominantIncreasedVenousThrombosisYoungAgeofThrombosisNoPredisposingFactorstoThrombosisIncreasedThrombinGenerationPositiveFamilyHistoryRecessiveNohistoryofthrombosisNofamilyhistoryNeonatalPurpuraFulminansIncreasedThrombinGeneration2021/8/12119、人的价值，在招收诱惑的一瞬间被决定。2023/2/32023/2/3Friday,February3,202310、低头要有勇气，抬头要有低气。2023/2/32023/2/32023/2/32/3/20234:45:24PM11、人总是珍惜为得到。2023/2/32023/2/32023/2/3Feb-2303-Feb-2312、人乱于心，不宽余请。2023/2/32023/2/32023/2/3Friday,February3,202313、生气是拿别人做错的事来惩罚自己。2023/2/32023/2/32023/2/32023/2/32/3/202314、抱最大的希望，作最大的努力。03二月20232023/2/32023/2/32023/2/315、一个人炫耀什么，说明他内心缺少什么。。二月232023/2/32023/2/32023/2/32/3/202316、业余生活要有意义，不要越轨。2023/2/32023/2/303February202317、一个人即使已登上顶峰，也仍要自强不息。2023/2/32023/2/32023/2/32023/2/32021/8/1212ACTIVATEDPROTEINCRESISTANCE1stdescribedbyDahlback,1994Hallmark:FailureofactivatedProteinCtoprolongaPTTFirstnotedinscreeningofplasmasamplesofpatientswithincreasedclottingFunctionaldefectdescribedbeforeproteindefectnoted2021/8/1213ACTIVATEDPROTEINCRESISTANCEBertinaetaldescribedgeneticdefectMutationofArg506GlnNamedFactorVLeidenFoundin>98%ofpatientswithAPCResistance2021/8/1214ACTIVATEDPROTEINCRESISTANCEExtremelycommon(5-20%ofCaucasianpopulationwithmutation)Increasesriskofvenousthromboembolism(VTE)c.4xinheterozygousform,moreinhomozygousCanexistincombinationwithotherdefects(proteinC,proteinS,ATIII,plasminogen)Incombination,hassynergisticeffectonotheranticoagulantproteindeficiencies2021/8/1215FACTORVaINACTIVATIONFactorVaiFVaAPCProSPLPROTEINC-MECHANISMOFACTION2021/8/1216FACTORVIIIaINACTIVATIONFactorVIIIaiFVIIIaAPCProSPLFactorVPROTEINC-MECHANISMOFACTION2021/8/1217HYPERCOAGULABLESTATES

AcquiredAnticardiolipinSyndromeMalignancyImmobilizationTTPDICOralContraceptiveTherapyProstheticValvesPNHMyeloproliferativediseasesNephroticSyndromeInflammatoryDiseasesAtherosclerosisSurgeryDiabetesmellitus2021/8/1218ACQUIREDHYPERCOAGULABLESTATES

MechanismsC4bBindingProtein-AcutePhaseReactantIncreasesininflammatorydiseasesBindstoProteinSBoundProteinSinactiveascofactorInflammationIncreasedIL-1&TNFBothdownregulatethrombomodulinThrombinbecomesprocoagulantinsteadofanticoagulantprotein2021/8/1219ANTITHROMBOTICTHERAPYPreventive-StopfurtherclotformationHeparin/LowmolecularweightheparinWarfarinAspirinHirudin/ArgatrobanThrombolytic-LyseclotalreadyformedStreptokinaseUrokinaseTissueplasminogenactivator2021/8/1220HEPARINTHERAPYEnhancesactivityofATIIIParenteraladministrationrequiredOnsetofactionimmediateMonitoraPTTLowerdosemayworkinpatientswithoutactivethrombosis2021/8/1221HEPARINTHERAPY

ComplicationsBleedingCausesmildplateletdysfunctionThrombocytopeniacommonOsteoporosiscommonwithlong-termuseHeterogeneousmixture;thereforedosingproblematic2021/8/1222HEPARINTHERAPY

LowMolecularWeightHeparin-AdvantagesLessheterogeneousthanheparinLessinhibitionofplateletfunctionLongerhalflife-Cangive1-2x/dayMuchlessthrombocytopenia?safer,equallyeffective2021/8/1223HEPARIN

LowMolecularWeightHeparin-DisadvantagesBleeding-?Lessthanwithheparin(probablynot)MostcrossreactwithheparinRE:

thrombocytopeniaEachpreparationisdifferentLessoverallexperiencewiththedrug2021/8/1224LEPIRUDIN/ARGATROBANSpecificthrombininhibitorsInhibitthrombinboundtofibrinInhibitsplateletactivationbythrombinBothcurrentlyapprovedforheparin-inducedthrombocytopenia2021/8/1225COUMADIN(warfarin)

MechanismofActionInhibitsVitaminKdependentcarboxylaseactivityPreventsreductionofVitaminKHumanssecretedes--carboxyglutamicacid,aninactiveproteinDOESNOTAFFECTPROTEINSALREADYSYNTHESIZEDMonitorusingprothrombintimeMultipleinteractionswithotherdrugsAntidote-VitaminK2021/8/1226THROMBOLYTICTHERAPYStreptokinasePurifiedfrombacteria(Streptococcus)Bindstoplasminogen,&complexactivatesasecondplasminogenmoleculetoplasminHighincidenceofallergicreactionsUrokinasePurifiedfromurineinitiallyRecombinantformnowavailableActivatesplasminogendirectlyTissueplasminogenactivatorMadebyendothelialcellsIncreasedaffinityforfibrin-boundplasminogenrelativefibrinspecificityRecombinantformavailableActivatesplasminogendirectly2021/8/1227THROMBOLYTICTHERAPY

ActionsUsedinmyocardialinfarctionLysescoronarythrombiImproves/preservesLVfunctionDecreasesmortalityHighrateofreocclusion-espwithTPALyseshemostaticplugseverywhereIncreasedincidenceofbleeding-espCNSLowersplasmafibrinogen?whichdrugissuperior2021/8/1228DICAcuteShockSepsisAllergicreactionsMismatchedtransfusionObstetricalproblemsTraumaBurnsExtracorporealcirculationAcidosisPurpurafulminansSubacute/ChronicAcuteleukemiaCarcinomasHemangiomataAorticaneurysms????liverdisease2021/8/1229ACUTEDICAlmostalwayssecondaryConsumptivecoagulopathyDecreasesinbothcoagulants&anticoagulantsSeveritymayrelatetolevelsofanticoagulants2021/8/1230DIC

PlasminogenActivationFXIIFXIIaPrekallikreinKallikreinPlasminogenPlasminUrokinaseTPA2021/8/1231FIBRINOGENSPLITPRODUCTSFibrinogen,340,000FragmentX,250,000FragmentY,150,000FragmentD,90,000FragmentD,90,000FragmentE,50,0002021/8/1232DEFIBRINATION

MechanismsReleaseofTissueProcoagulantsTumorFetal/Placental/AmnioticProstaticPancreaticWBCRBCShockDamagetoVascularTreeSepticemiaAorticaneurysmHemangiomaTumoremboli?ShockDecreasedClearanceLiverdisease?Shock2021/8/1233DIC

Testing(Acute)2021/8/1234DIC

TherapyDependsonprimarymanifestationThrombosis-AnticoagulanttherapyBleeding-ReplacementtherapyPrimarytreatmentTREATUNDERLYINGDISEASEReplacementCryoprecipitate-FibrinogenFreshfrozenplasma-OtherfactorsPlateletsHeparinRarelyindicated2021/8/1235LIVERDISEASEFactordeficiencies-2DecreasedsynthesisAbnormalfibrinogenExcesssialicacidProlongedthrombintimeLowGradeDIC-DifficultDxtomakeIncreasedfibrinolysis

Plasminogenactivatorinhibitor

-2antiplasmin

tissueplasminogenactivator2021/8/12369、人的价值，在招收诱惑的一瞬间被决定。03-2月-2303-2月-23Friday,February3,