DIC弥散性血管内凝血2课件

Disseminatedintravascularcoagulation1DisseminatedintravascularcoaIntravascular

Extravascular

NormalcirculationHemostasisliquiditysolidity(coagulation)Normal

Normal

Blood

AbnomalAbnomal

solidity(coagulation)liqidityThromboticdiseaseHemorrhagicdisease

Intravascular

Extravascular2IntravascularThefunctionofcoagulationsystem

(Extrinsic,Intrinsicpathwayandplatelet)

Thefunctionofanticoagulation

(TFPI,PCsystem,ATIIIandfibrinolyticsystem)TheregulationofbalancebyVECThekeyfactors

forbalanceofcoagulation-anticoagulation:3ThefunctionofcoagulationsThechainreactionofbloodcoagulationFXI

FXIaFVII/FVIIa-TF-Ca2+(onmembrane)↓↓

FIXFIXaTFPI-FXaFVIIIaCa2+-PL

prothrombin

(FII)PCIFXFxaPL-Ca2+FvaAPC(PS)XIII

thrombinTM-on-VECXIIIaATIIIPC

FbnFbnFMFbg(FI)

(cross-linked)(soluble)TF=tissuefactor;TFPI=TFpathwayinhibitor;Fbg=fibrinogen;Fbn=fibrin;FM=fibrinmonomer;PC=proteinC;APC=activatedPC;PS=proteinS;PCI=PCinhibitorATIII=antithrombinIII;TM=thrombomodulin;VEC=vascularEC4ThechainreactionofbloodcoThefibrinolysissystem

Plasminogen(PLg)(Extra-activatingpathway)

(Intra-activatingpathway)

tissue-typeplasminogenactivationofclottingsystem

activator(t-PA)XIa

urokinase-typeplasminogenthrombinactivator(u-PA)XIIaXII(Exogenousactivator)

urokinase(UK)kallikrein(KK)streptokinase(SK)

prekallikrein(PK)

Plasmin(Pln)

FbgFbnFDP(fibrinogen)(fibrin)(Fbg/Fbndegradationproducts)

5ThefibrinolysissystemInhibitXa,VIIa,TFInhibitplatelet

aggregationFibrinolysisPreventfibrinclotformationTraumaAdrenalinThrombinADPNO,PGI2

Xa,IIaPlasminPlasminoginActivatorst-PA,u-PAInactivateVa,VIIIaPSThrombinPCAPC

TMInhibitXa,IIaATIII+HeparinTFPIAnticoagulantfunctionofendothelialcells6InhibitInhibitplatelet

aggrSection1.

ConceptandcausesofDIC

7Section1.ConceptandcausToday’sQuestionQuestion1.WhatisDIC?8Today’sQuestion81.ConceptofDICDisseminatedintravascularcoagulation(DIC)

Asyndrome

thatresultsfromthedisturbanceofkineticbalanceofcoagulationandfibrinolyticprocesses.Characterizedbyextensiveintravascularmicrothrombosisandimpairmentofhemostasia.Itsinitiallinkisactivationofclottingsysteminthebody91.ConceptofDICDisseminateextensivemicrothrombinextensivehemorrhage

organdysfunctionShockaneamiaNormalbalanceofcoagulation-anticoagulationHypocoagulablestateHypercoagulablestateUnbalanceofcoagulation-anticoagulationandDICextensiveactivationofclottingfactorsandplateletsconsumptionofclottingfactorsandplateletssecondaryfibrinolysishemorrhageorgandysfunctionShockaneamia10extensivemicrothrombinThereforeDICusuallyassociatedsimultaneouslywithbothhemorrhageandthrombosis.Itsclinicalpresentationsinclude:1)extensivehemorrhageatskin,mucosaandinternalorgans(viscera);2)shock;3)organdysfunction;4)aneamia.

Anextensiveactivationofcoagulationprocesscausedbytheenteringofcoagulation-promotingsubstancesintocirculationAnincreasedconsumptionofclottingfactorsandplatelets,depositionoffibrinandsecondaryfibrinolysis.resultsin11ThereforeDICusuallyas2.

CausesofDIC

including:infectiousdiseases,extensivetissueinjury,obstetriccomplications,malignanttumors,acuteleukemia,shock,hepaticandrenaldiseases,collagendisease,metabolicdiseases,cardiovasculardiseases,intravascularhemolysisEtiologicDiseaseofDICDiseasesorpathologicprocesswhichmayleadtoDICTriggering

FactorAnyfactorswhichmaytriggerorpromoteDICoccur122.

CausesofDIC

including:

including:infectiousdiseases,extensivetissueinjury,obstetriccomplications,malignanttumors,acuteleukemia,shock,hepaticandrenaldiseases,collagendisease,metabolicdiseases,cardiovasculardiseases,intravascularhemolysis2.

CausesofDICTriggering

FactorAnyfactorswhichmaytriggerorpromoteDICoccurEtiologicDiseaseofDICDiseasesorpathologicprocesswhichmayleadtoDIC1)Tissueinjuryandreleasetissuefactor(TF)2)Vascularendothelialcells(VEC)injury3)bacterialendotoxin4)Ag-Abcomplex5)Proteinhydrolyticenzymes6)Particleorcolloid7)Virusandothermicrobe13

including:2.

CausesofDICSection2.PathogenesisofDIC

14Section2.PathogenesisofDIThemechanismofDICisverycomplexandremainsunclearuptonow.

Thecommonpathogenicprocessinclude:1)Triggeringclottingactivation,producingnumerousinsolublefibrin(Fbn)andactivatingplatelets;2)ThegeneratedFbndepositinmicrovesselsandismorethanhydrolyticabilityoffibrinolysin;3)AlterationoffibrinolysisfunctionduringtheDICprocesswhichisrelatedtothepathologicprocessofmicro-thrombosisandbleedingtendency.15ThemechanismofDICisvery1.Activationofclottingsystem

Assoonasactivation,theclottingresponsewillbemagnifiedbycascadeorlimitedbynegativefeedback.Theclottingsystemisliabletobeactivatedinthemicrovessels,leadingtomicro-thrombusformation.Thecausesandpathogenesisofclottingsystemactivationincluding:

(1)Tissueinjury(2)Vascularendothelialcellsinjury(3)Otherpathwaytoactivateclottingsystem161.Activationofclottingsyst(1)TissueinjurySeveretrauma,burns,surgicaloperation,obstetricaccident,tumortissuenecrosisormetastasis,bloodcellinjury(radiationorchemicaltherapyforleukemia)

ExcessivedestructionoftissueNumerousTFenteringthebloodActivatingclottingreactions

Besides,lysozymesreleasedbylysosomeofdamagedcellsmayalsopromotetheactivationofclottingsystem.17(1)TissueinjurySeveretraumaInfectious,endotoxinemia,Ag-Abcomplex,persistentischemiaandhypoxia,acidosis

extensivedamageofvascularendothelialcells

.

activating

clotting

reactions(activatingMo/Mf,PMN,T-lymphocyte→releaseTNF,IL-1,IFN,PAF,C3a,C5a,O2·－)

(2)VascularendothelialcellsinjuryreleasingTFsubendothelialexposureplateletsadhesionAggregationandrelease18Infectious,endotoxinemia,Ag-①

ActivationofMo/Mf,WBC→releaseTF,lysozymes②

Malignanttumors→releaseTF,cancerprocoagulant③

Hemorrhagicpancreatitis,cancerofpancreas→releasetrypsin(mayactivateprothrombindirectly)④

Exogenoustoxin→activateFX,prothrombinortransferFbgtoFbndirectly⑤Extensive

hemolysis→releaseADP→activateplateletsreleaseerythrin→TF-likeeffect

(3)Otherpathwaytoactivateclottingsystem19①ActivationofMo/Mf,WBC→r2.ChangeofvasomotorialactivityandbloodfluidityVECinjury

EDRF,PGI2↓,ET↑Plateletactivated

TXA2↑Bloodflow↓(vasoconstriction)orstasis(vasodilation)eliminateofcoagulantoractivateclottingfactors↓PAF,histamin,BK↑

vascularpermeability↑

(BK:bradykinin)DepositofFbn↑Bloodcondense,Viscosity↑202.Changeofvasomotorialacti3.Disturbanceoffibrinolysis

(1)

Localfibrinolysis↓→clottingVECinjury→localanticoagultiveandfibrinolyticfunction↓→depositofFbn↑→microthrombusformation

(2)

Secondaryfibrinolysis↑→bleeding①FXIa,thrombin,KK,etc.→promotetransferPLgtoPLn②VECreleaset-PA,u-PA→transferPLgtoPLn③ProteinCactivatedbythrombin(viaVEC-TM)→formactivatedproteinC(APC)→anticoagulationandpromotefibrinolysis.213.Disturbanceoffibrinolysi

PathologicalFactors

extensiveactivationofclottingfactorsandplatelets

intravascularcoagulationconsumptionofclottingsecondaryfactorsandplateletsfibrinolysis

extensivehemorrhageaneamiashockorgandysfunction(Disseminatedintravascularcoagulation,DIC)HypercoagulablestateHypocoagulablestate22

Section3.

PrimaryclinicalpresentationsofDIC23Section3.PrimarycliniDICmayleadtofourconsequencesasfollows:1.Disturbanceofcoagulation---------

Bleeding2.Disturbanceofmicrocirculation---Shock3.multipleorgansdysfunction--------MOD4.Microangiopathichemolytic--------Anemia24DICmayleadtofourconsequen1.Disturbanceofcoagulation---BleedingTheprimeandcommonsymptomofDICisbleeding.ThefeaturesofbleedinginDIC:(1)

Highoccurrencerate(70~80%)(2)

Difficulttoexplainbyprimarydisease(3)

Manifoldbleedingtypes(4)

Difficulttobecuredbyregularhemostatics251.Disturbanceofcoagulation-ThecausesofbleedinginDICincluding:(1)Excessiveconsumptionofcoagulationsubstances(clottingfactorsandplatelets);(2)Secondaryenhanceoffibrinolysis(3)Anticoagulativeeffectsoffibrindegradationproducts;Fbg/FbnFDP(fragmentX,Y,E,D)X,Y+FM→solublefibrinmonomercomplex(SFMC)(4)InjuryofcapillarywallcausedbyprimarycauseofDICandsecondaryhypoxia,acidosis,cytokinesandfreeradical.

PLnThrombinFbg(FI)FMsFbnFbn

26ThecausesofbleedinginDIC

DIC,especiallyacuteDIC,isoftenassociatedwithshock

ShockinseverdegreeorinlatestagecanalsopromotetheproductionofDIC2.Dsturbanceofmicrocirculation-shock27DIC,especiallyacuteDIC,(1)Extensivemicrothrombusformation(2)Extensivebleeding

permeability

plasmaexudation(3)Activatingkinin,histamin

shock

microvesseldilation(4)FDP(A,B,C)(5)

Microthrombuscoronaryperfusion

pulmonaryhypertensioncardiacload

Ischemia,hypoxia&acidosis

returnedbloodtoheart

effectivecirculationbloodvolume

peripheralresistance

heartfunctionandcardiacoutput

28(1)Extensivemicrothrombusret3.Multipleorgansdysfunction(MOD)Perfusionimpairment/ischemia-reperfusioninjuryactivationofWBC/inflammatorymediatorIschemictissuedamageMOD

MODisusuallythemostimportantcauseofdeathinDIC.293.Multipleorgansdysfunction

OccurrenceofMODisrelatedtofollowingfactors:(1)

Extensivemicrothrombiformationintheorgans→ischemia,hypoxia,impairmentofmetabolismandfunction,orevennecrosisandorganfailure.

(2)

PathologicalterationcausedbyeffectsoforganseachotherDIC

Lungs

pulmonarycirculation

Hearthypoxia,acidosis

Otherorgans

(3)Pathologicalterationandsymptomsofprimarydiseases(whichshouldberuleoutfromMOD).inflammationofthelungsdysfunctionofrespirationse.g.Lung→ARDS;kidney→ARF;Digestivesystem→nausea,vomiting,diarrhea,hemorrhage;Liver→jaundiceandhepaticfailure;Heart→CO↓,PAWP↑;Pituitarynecrosis→Sheehan'ssyndrome;Adrenalcortexhemorrhagicnecrosis→Waterhouse-friderchsen'ssyndrome;CNS→bleeding,edema(somnolence,coma,convulsion)

30

OccurrenceofMODisrelate

OccurrenceofMODisrelatedtofollowingfactors:

(1)

Extensivemicrothrombiformationintheorgans→ischemia,hypoxia,impairmentofmetabolismandfunction,orevennecrosisandorganfailure.

(2)

PathologicalterationcausedbyeffectsoforganseachotherDIC

Lungs

pulmonarycirculation

Hearthypoxia,acidosis

Otherorgans

(3)Pathologicalterationandsymptomsofprimarydiseases(whichshouldberuleoutfromMOD).inflammationofthelungsdysfunctionofrespirations31

OccurrenceofMODisrelate

OccurrenceofMODisrelatedtofollowingfactors:

(1)

Extensivemicrothrombiformationintheorgans→ischemia,hypoxia,impairmentofmetabolismandfunction,orevennecrosisandorganfailure.

(2)

PathologicalterationcausedbyeffectsoforganseachotherDIC

Lungs

pulmonarycirculation

Hearthypoxia,acidosis

Otherorgans

(3)Pathologicalterationandsymptomsofprimarydiseases(whichshouldberuleoutfromMOD).inflammationofthelungsdysfunctionofrespiration32

OccurrenceofMODisrelate4.Microangiopathichemolyticanemia

RBCmaydamagedastheymovethroughthefibrinnetandresultinastrikinghemolyticanemia,withaspecialmorphologicabnormalityoftheRBCcalledschistocyte.(Twistedcells,crenatedcells,triangularcells,helmet-shapedcells,andmicrospherocytes)Thehemolysiscanprovidemoretriggeringmaterial(ADPandmembranephospholipid)forcontinuedintravascularcoagulation.334.MicroangiopathichemolyticSection4.FactorsinfluencingthedevelopmentofDIC34Section4.FactorsinfluencingMononuclearphagocytesystemdysfunctionSeveredysfunctionoftheliverHypercoagulablestateDisorderofmicrocirculationFibrinolyticsystem

dysfunction35MononuclearphagocytesystemdProlongedandexcessiveRepeatedinfectionadministrationofglucocorticoidhormonesSeverehepaticdisease

ImpairingMo/MfsystemfunctionDisabletocleanclot-promotingsubstances(Fbg,Fbn,FMandFDP,etc.)

GeneralizedShwartzmanreaction,GSR(1)Mononuclearphagocytesystemdysfunction36Prolongedandexcessive(2)

Severedysfunctionoftheliver1)Pathogenicfactorsofliverdiseasesuchasvirus,Ag-Abcomplexandsomedrugsmayactivateclottingsystem.2)AcutehepaticnecrosismayreleaseTFandlysozymes3)Decreasedabilityofproductionandeliminationofclottingandanticoagulativefactors.37(2)

SeveredysfunctionofthePrimary:geneticATIII,PC,PSdeficiency,etc.Secondary:nephroticsyndrome,malignanttumors,leukemia,toxemiaofpregnancy,etc.(3)

Hypercoagulablestate38Primary:geneticATIII,PC,1)VECinjury→Activationofclottingsystem;2)Bloodflow↓orstasis→accumulationofactivatedclotfactors;3)Dysfunctionofliver,kidney→abilityofeliminateclotfactorsandfibrinolyticproducts

4)Vasomotorialimpairment→feasibletoFbndepositandmicrothrombiformation.(5)Fibrinolyticsystem

dysfunctione.g.senility,smoking,latestageofpregnancy,diabetes,

misuseoffibrinolyticinhibitor,etc.(4)

Disorderofmicrocirculation391)VECinjury→ActivationofSection5StagesandtypesofDIC40Section5StagesandtypesofD1.StagesofDIC

Pathophysiology

ClinicalLaboratoryfindings

(1)Hypercoagulablestage(2)Consuminghypocoagulablestage(3)SecondaryfibrinolyticStage

ExessiveactivationofclottingfactorsandformationofmicrothrombinIncreasedconsumption

ofclottingfactorsandplateletConsiderableformationofplasminandFDP

411.StagesofDIC

1.StagesofDIC

Pathophysiology

Clinical

Laboratoryfindings(1)Hypercoagulablestage(2)Consuminghypocoagulablestage(3)SecondaryfibrinolyticStage

HypercoagulableBleedingBleedingmarkedly421.StagesofDIC

1.StagesofDIC

Pathophysiology

ClinicalLaboratoryfindings

(1)Hypercoagulablestage(2)Consuminghypocoagulablestage(3)SecondaryfibrinolyticStage

Shortenedclottingandrecalcificationtime;IncreasedadherenceofplateletProlongedclottingandrecalcificationtimeReductionofplateletcountandFbgnarkedlyShortenedCLT,ELT;ProlongedTT3Ptest(+),IncreasedFDP

CLT=clot-lysistimeELT=euglobulin-lysistimeTT=thrombintime431.StagesofDIC

ProductionofFDPand3ptest

(plasmaprotamineparacoagulationtest)

FibrinogenThrombin

Fibrinmonomer(FM)Fibrinpolymer

PlasminXIIIaFDP-X,Y,D,E

Stabilizedfibrin(bloodclotting)X+FM→solublefibrinmonomercomplex(SFMC)Protamin

SFMCX+FM→bloodclotting44ProductionofFDPand3ptest

Developtime

Commoncauses

Clinicfeature

2.TypesofDICAccordingtotherateofdevelopment,divideinto3typesAcute

Subacute

Chronicafewhourstodayswithindaystoweeksmonths45

Developtime

Commoncauses

Clinicfeature

2.TypesofDICAccordingtotherateofdevelopment,divideinto3typesAcute

Subacute

Chronicmalignanttumorscollagenosismetastasisofmalignanttumors;retaineddeadfetussevereinfectionortraumaammioticfluidembolism46

Developtime

Commoncauses

Clinicfeature

2.TypesofDICAccordingtotherateofdevelopment,divideinto3typesAcute

Subacute

Chronicmildorconcealedmicrothrombinformationbleedingshock,bloodingexacerbaterapidly47

:

Accordingtocompensatorystate,divideinto3types

Clottingfactorsandplatelet

Clinicalsituations

compensatory

Consumption=productiondiscompensatoryConsumption>production

overcompensatory

Consumption<production48:48:

Accordingtocompensatorystate,divideinto3types

Clottingfactorsandplatelet

Clinicalsituations

compensatory

MildDICdiscompensatoryAcuteDIC

overcompensatory

ChronicDICorrecovery49:49Section

6.PrinciplesofpreventionandtreatmentofDIC50Section6.Principlesofpreven1.PathophysiologybasesofdiagnosisofDIC

(1)

Existenceofcausativediseases;(2)

ExistenceofcharacteristicsymptomsandsignsofDIC(3)Positivelaboratoryfindings:plateletcount,Fbg↓↓,PT&TT↑,3Ptest(+),CLT&ELT↓

511.Pathophysiologybases2.Pathophysiologybasesofprevention

andtreatmentofDIC

(1)

Earlierdiagnosisandtreatment(2)

Treatmentofthecausativedisease(3)Anticoagulationtreatment(toblocktheviciouscycle

ofclottingresponse)(4)

Protectionoforganfunction(5)

Supplementoffreshbloodorplasma,concentratedplateletorclottingfactors(torecovercoagulation-anticoagulationbalance)

(6)AntifibrinolysistreatmentBacktocovernextchapter52