pathophysiologypart414dic彌散性血管內(nèi)凝血課件

1Chapter16.

Disseminatedintravascularcoagulation2Intravascular

Extravascular

NormalcirculationHemostasisliquiditysolidity(coagulation)Normal

Normal

Blood

AbnomalAbnomal

solidity(coagulation)liqidityThromboticdiseaseHemorrhagicdisease

Intravascular

Extravascular3Thefunctionofcoagulationsystem

(Extrinsic,Intrinsicpathwayandplatelet)

Thefunctionofanticoagulation

(TFPI,PCsystem,ATIIIandfibrinolyticsystem)TheregulationofbalancebyVECThekeyfactors

forbalanceofcoagulation-anticoagulation:5Thefibrinolysissystem

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)

6InhibitXa,VIIa,TFInhibitplatelet

aggregationFibrinolysisPreventfibrinclotformationTraumaAdrenalinThrombinADPNO,PGI2

Xa,IIaPlasminPlasminoginActivatorst-PA,u-PAInactivateVa,VIIIaPSThrombinPCAPCTMInhibitXa,IIaATIII+HeparinTFPIAnticoagulantfunctionofendothelialcells7Section1.

ConceptandcausesofDIC

91.ConceptofDICDisseminatedintravascularcoagulation(DIC)

Asyndrome

thatresultsfromthedisturbanceofkineticbalanceofcoagulationandfibrinolyticprocesses.Characterizedbyextensiveintravascularmicrothrombosisandimpairmentofhemostasia.Itsinitiallinkisactivationofclottingsysteminthebody10extensivemicrothrombinextensivehemorrhage

organdysfunctionShockaneamiaNormalbalanceofcoagulation-anticoagulationHypocoagulablestateHypercoagulablestateUnbalanceofcoagulation-anticoagulationandDICextensiveactivationofclottingfactorsandplateletsconsumptionofclottingfactorsandplateletssecondaryfibrinolysishemorrhageorgandysfunctionShockaneamia11ThereforeDICusuallyassociatedsimultaneouslywithbothhemorrhageandthrombosis.Itsclinicalpresentationsinclude:1)extensivehemorrhageatskin,mucosaandinternalorgans(viscera);2)shock;3)organdysfunction;4)aneamia.

Anextensiveactivationofcoagulationprocesscausedbytheenteringofcoagulation-promotingsubstancesintocirculationAnincreasedconsumptionofclottingfactorsandplatelets,depositionoffibrinandsecondaryfibrinolysis.resultsin13

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)Virusandothermicrobe14Section2.PathogenesisofDIC

15ThemechanismofDICisverycomplexandremainsunclearuptonow.

Thecommonpathogenicprocessinclude:1)Triggeringclottingactivation,producingnumerousinsolublefibrin(Fbn)andactivatingplatelets;2)ThegeneratedFbndepositinmicrovesselsandismorethanhydrolyticabilityoffibrinolysin;3)AlterationoffibrinolysisfunctionduringtheDICprocesswhichisrelatedtothepathologicprocessofmicro-thrombosisandbleedingtendency.17(1)TissueinjurySeveretrauma,burns,surgicaloperation,obstetricaccident,tumortissuenecrosisormetastasis,bloodcellinjury(radiationorchemicaltherapyforleukemia)

ExcessivedestructionoftissueNumerousTFenteringthebloodActivatingclottingreactions

Besides,lysozymesreleasedbylysosomeofdamagedcellsmayalsopromotetheactivationofclottingsystem.18Infectious,endotoxinemia,Ag-Abcomplex,persistentischemiaandhypoxia,acidosis

extensivedamageofvascularendothelialcells

.

activating

clotting

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

(2)VascularendothelialcellsinjuryreleasingTFsubendothelialexposureplateletsadhesionAggregationandrelease19①

ActivationofMo/Mf,WBC→releaseTF,lysozymes②

Malignanttumors→releaseTF,cancerprocoagulant③

Hemorrhagicpancreatitis,cancerofpancreas→releasetrypsin(mayactivateprothrombindirectly)④

Exogenoustoxin→activateFX,prothrombinortransferFbgtoFbndirectly⑤Extensive

hemolysis→releaseADP→activateplateletsreleaseerythrin→TF-likeeffect

(3)Otherpathwaytoactivateclottingsystem213.Disturbanceoffibrinolysis

(1)

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

(2)

Secondaryfibrinolysis↑→bleeding①FXIa,thrombin,KK,etc.→promotetransferPLgtoPLn②VECreleaset-PA,u-PA→transferPLgtoPLn③ProteinCactivatedbythrombin(viaVEC-TM)→formactivatedproteinC(APC)→anticoagulationandpromotefibrinolysis.22

PathologicalFactors

extensiveactivationofclottingfactorsandplatelets

intravascularcoagulationconsumptionofclottingsecondaryfactorsandplateletsfibrinolysis

extensivehemorrhageaneamiashockorgandysfunction(Disseminatedintravascularcoagulation,DIC)HypercoagulablestateHypocoagulablestate23Section3.

PrimaryclinicalpresentationsofDIC251.Disturbanceofcoagulation---BleedingTheprimeandcommonsymptomofDICisbleeding.ThefeaturesofbleedinginDIC:(1)

Highoccurrencerate(70~80%)(2)

Difficulttoexplainbyprimarydisease(3)

Manifoldbleedingtypes(4)

Difficulttobecuredbyregularhemostatics26ThecausesofbleedinginDICincluding:(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

293.Multipleorgansdysfunction(MOD)Perfusionimpairment/ischemia-reperfusioninjuryactivationofWBC/inflammatorymediatorIschemictissuedamageMOD

MODisusuallythemostimportantcauseofdeathinDIC.30

OccurrenceofMODisrelatedtofollowingfactors:(1)

Extensivemicrothrombiformationintheorgans→ischemia,hypoxia,impairmentofmetabolismandfunction,orevennecrosisandorganfailure.

(2)

PathologicalterationcausedbyeffectsoforganseachotherDICLungspulmonarycirculationHearthypoxia,acidosisOtherorgans

(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)

31

OccurrenceofMODisrelatedtofollowingfactors:

(1)

Extensivemicrothrombiformationintheorgans→ischemia,hypoxia,impairmentofmetabolismandfunction,orevennecrosisandorganfailure.

(2)

PathologicalterationcausedbyeffectsoforganseachotherDICLungspulmonarycirculationHearthypoxia,acidosisOtherorgans

(3)Pathologicalterationandsymptomsofprimarydiseases(whichshouldberuleoutfromMOD).inflammationofthelungsdysfunctionofrespirations32

OccurrenceofMODisrelatedtofollowingfactors:

(1)

Extensivemicrothrombiformationintheorgans→ischemia,hypoxia,impairmentofmetabolismandfunction,orevennecrosisandorganfailure.

(2)

PathologicalterationcausedbyeffectsoforganseachotherDICLungspulmonarycirculationHearthypoxia,acidosisOtherorgans

(3)Pathologicalterationandsymptomsofprimarydiseases(whichshouldberuleoutfromMOD).inflammationofthelungsdysfunctionofrespiration334.Microangiopathichemolyticanemia

RBCmaydamagedastheymovethroughthefibrinnetandresultinastrikinghemolyticanemia,withaspecialmorphologicabnormalityoftheRBCcalledschistocyte.(Twistedcells,crenatedcells,triangularcells,helmet-shapedcells,andmicrospherocytes)Thehemolysiscanprovidemoretriggeringmaterial(ADPandmembranephospholipid)forcontinuedintravascularcoagulation.34Section4.FactorsinfluencingthedevelopmentofDIC35MononuclearphagocytesystemdysfunctionSeveredysfunctionoftheliverHypercoagulablestateDisorderofmicrocirculationFibrinolyticsystem

dysfunction36ProlongedandexcessiveRepeatedinfectionadministrationofglucocorticoidhormonesSeverehepaticdisease

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

GeneralizedShwartzmanreaction,GSR(1)Mononuclearphagocytesystemdysfunction37(2)

Severedysfunctionoftheliver1)Pathogenicfactorsofliverdiseasesuchasvirus,Ag-Abcomplexandsomedrugsmayactivateclottingsystem.2)AcutehepaticnecrosismayreleaseTFandlysozymes3)Decreasedabilityofproductionandeliminationofclottingandanticoagulativefactors.38Primary:geneticATIII,PC,PSdeficiency,etc.Secondary:nephroticsyndrome,malignanttumors,leukemia,toxemiaofpregnancy,etc.(3)

Hypercoagulablestate391)VECinjury→Activationofclottingsystem;2)Bloodflow↓orstasis→accumulationofactivatedclotfactors;3)Dysfunctionofliver,kidney→abilityofeliminateclotfactorsandfibrinolyticproducts

4)Vasomotorialimpairment→feasibletoFbndepositandmicrothrombiformation.(5)Fibrinolyticsystem

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

misuseoffibrinolyticinhibitor,etc.(4)

Disorderofmicrocirculation40Section5StagesandtypesofDIC411.StagesofDIC

Pathophysiology

ClinicalLaboratoryfindings

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

ExessiveactivationofclottingfactorsandformationofmicrothrombinIncreasedconsumption

ofclottingfactorsandplateletConsiderableformationofplasminandFDP

421.StagesofDIC

Pathophysiology

Clinical

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

HypercoagulableBleedingBleedingmarkedly431.StagesofDIC

Pathophysiology

ClinicalLaboratoryfindings

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

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

CLT=clot-lysistimeELT=euglobulin-lysistimeTT=thrombintime44ProductionofFDPand3ptest

(plasmaprotamineparacoagulationtest)

FibrinogenThrombin

Fibrinmonomer(FM)Fibrinpolymer

PlasminXIIIaFDP-X,Y,D,E

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

SFMCX+FM→bloodclotting45

Developtime

Commoncauses

Clinicfeature

2.TypesofDICAccordingtotherateofdevelopment,divideinto3typesAcute

Subacute

Chronicafewhourstodayswithindaystoweeksmonths46

Developtime

Commoncauses

Clinicfeature

2.TypesofDICAccordingtotherateofdevelopment,divideinto3typesAcute

Subacute

Chronicmalignanttumorscollagenosismetastasisofmalignanttumors;retaineddeadfetussevereinfectionortraumaammioticfluidembolism47

Developtime

Commoncauses

Clinicfeature

2.TypesofDICAccordingtotherateofdevelopment,divideinto3typesAcute

Subacute

Chronicmildorconcealedmicrothrombinformationbleedingshock,bloodingexacerbaterapidly48:

Accordingtocompensatorystate,divideinto3types

Clottingfactorsandplatelet

Clinicalsituations

compensatory

Consumption=productiondiscompensatoryConsumption>production

overcompensatory

Consumption<production49:

Accordingtocompensatorystate,divideinto3types

Clottingfactorsandplatelet

Clinicalsituations

compensatory

MildDICdiscompensatoryAcuteDIC

overcompensatory

ChronicDICorrecovery50Section

6.PrinciplesofpreventionandtreatmentofDIC511.PathophysiologybasesofdiagnosisofDIC

(1)

Existenceofcausativediseases;(2)

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

522.Pathophysiologybasesofprevention

andtreatmentofDIC

(1)

Earlierdiagnosisandtreatment(2)

Treatmentofthecausativedisease(3)Anticoagulationtreatment(toblocktheviciouscycle

ofclottingresponse)(4)

Protectionoforganfunction(5)

Supplementoffreshbloodorplasma,concentratedplateletorclottingfactors(torecovercoagulation-anticoagulationbalance)

(6)AntifibrinolysistreatmentBacktocovernextchapter53

Asyndromeresultingfromthedisturbancebalanceofcoagulationandfibrinolyticprocesses,characterizedbyextensiveintravascularmicrothrombosisandimpairmentofhemostasia,iscalleddisseminatedintravascularcoagulation.

DiseasesorpathologicprocesswhichmayleadtoDICarecalledetiologicdiseaseof