3.Disseminated Intravascular Coagulation (DIC) shock syndrome • Others: ... 5 overt DIC, 5 suggest non ... 3.Disseminated Intravascular Coagulation (DIC).pptx

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  • DisseminatedIntravascularCoagulation(DIC)

    Yingyong ChinthammitrFacultyofMedicineSiriraj hospital

    Bangkok,THAILAND

  • ISTH Advanced Training CourseDubai, UAE

    Disclosures for In compliance with COI policy, ISTH requires the following disclosures to the session audience:

    Research Support/P.I. No relevant conflicts of interest to declare

    Employee No relevant conflicts of interest to declare

    Consultant No relevant conflicts of interest to declare

    Major Stockholder No relevant conflicts of interest to declare

    Speakers Bureau No relevant conflicts of interest to declare

    Honoraria No relevant conflicts of interest to declare

    Scientific Advisory Board No relevant conflicts of interest to declare

  • Definition DICisanacquiredsyndromecharacterizedbytheintravascularactivationofcoagulationwithoutaspecificlocalizationandarisingfromdifferentcauses.Itcanoriginatefromandcausedamagetothemicrovasculature,whichifsufficientlysevere,canproduceorgandysfunction.

    TaylorFBJr,etal.Thromb Haemost 2001;86:1327

  • Figure 5. The patient counts and mortality rates according to the categories of the original and simplified versions of Japanese Society on Thrombosis and Hemostasis (JSTH) disseminated intravascular coagulation (DIC) diagnostic criteria. The bar graph shows the number of patients in each category, and the line graph represents the mortality rate. The mortality rate increased linearly for scores of 3 to 7 and exceeded 30% based on the simplified JSTH-DIC score of 4.

    Published in: Toshiaki Iba; Marcello Di Nisio; Jecko Thachil; Hideo Wada; Hidesaku Asakura; Koichi Sato; Daizoh Saitoh; Clin Appl Thromb Hemost Ahead of PrintDOI: 10.1177/1076029617720069Copyright 2017 SAGE Publications

    Sepsis-Associated DIC and Mortality Rate

  • Clinical conditions most frequently complicated by DICSepsis / severe infection Severe allergic / toxic

    reactionsTrauma / Burn / Heat stroke Severe immunologic

    reactions e.g., transfusion reaction

    Malignancy: Solid tumors,Acute leukemia

    Obstetric conditions:Amniotic fluid embolismAbruptio placentaeHELLP syndromeRetained dead fetus

    Vascular abnormalities:Kasabach-Merritt SyndromeOther vascular malformationsAortic aneurysms

  • TF

    Bacteria Cancer

    TraumaBurnsPlacenta

    PLT

    P-selectin

    TF

    NFB(IL)-1b, IL-8, MCP-1, TNF-, IL-1, IL-6, Adhesion protein

    Microvascular thrombi

    Monocyte

    TFPIAPC

    Antithrombin Fibrinolysis:tPAuPA

    PAI-1

    Coagulopathy, Thrombocytopenia

    Multiorganischemia e.g. ATN, Acute lung injury Bleeding

  • ClinicalManifestationsofDICVarydependingonUnderlyingdisorder

    AcutesevereDIC Sepsis,majortrauma,Obstetric,severeimmunologicresponse

    Diffusemultiorganbleeding,hemorrhagicnecrosis,thrombiinsmalltomedium/largebloodvessels

    ChronicDIC Malignancy,retaineddeadfetus,aneurysm

    MucinproducingAdenoCA venousthrombosis,NBTEarterialembolism

    APL bleeding

  • DICinInfectiousDisease Risk:immunocompromised,asplenia,newborns,(majortrauma/activemalignancy)

    Gramnegativebacteriae.g.P.aeruginosa,E.coli,Proteusvulgaris,Meningococcemia

    Grampositivebacteriae.g.StreptococcusAtoxicshocksyndrome

    Others:virus(e.g.Dengue),malaria,fungi VaryfromLababnormalities severeDICPurpurafulminans

  • DICinTrauma,Braininjury,Burns,HeatStroke

    Time interval betweenTraumaandmedicalintervention(e.g.evacuation,resuscitation)correlateswithdevelopmentandmagnitudeofDICRx:TFexposure,preventshock

    Trauma:earlyphase hyperfibrinolysis;laterphase hypercoagulablefromPAI1

    Headinjury:LabDICscorepredictsprognosis Heatstroke:endothelialcelldamage,TFfromheatdamagedtissues

  • DICinObstetricComplications Abruptio placentae:10%hasDIC;risk:oldermultiparous,hypertensioninpregnancy

    Amnioticfluidembolism:maternalmortality26%;Pulmonarya.occlusionanaphylactoidresponse/DICshock,convulsionbleeding

  • DICinMalignancy Risk:Tumor(mucinproducing,AL),Host(oldage),Rx(chemo),Complication(sepsis)

    TF +FVIIa IXa,Xa Cancerprocoagulant (cysteineprotease) Xa P,LselectininteractwithmucinPLT thrombi APL(>90%)>AML(32%)>ALL(1520%)

  • DICinAPL

    TF

    CP

    Activatecoagulation

    ReleaseIL1,TNF

    Endothelialthrombomodulin

    ProteinCanticoagulant

    Annexin II

    BindsplasminogenandtPA

    HyperFibrinolysis

    DIC

    Plasmin

    Bleeding

  • DICinVascularDisorders Aorticaneurysm TFinatheroscleroticplaque

    40%hadFDP,4%hadDIC RiskofDIC:large,dissected,expand

    KasabachMerritt giantcavernoushemangiomas consumePLTandfibrinogen;tPA releasedfromabnormalendotheliumintumorwalls hyperfibrinolysis

  • DICwithLiverDisease Severeliverdisease labasDIC

    Coagulationfactors Naturalanticoagulants ClearanceofIXa,Xa,XIa,tPA Thrombocytopeniafromhypersplenism,TPO

  • DICaccompaniesLiverDisease?PRO Halflifeofradiolabeledfibrinogen(reversedwithheparin)

    FailureofreplacementRxtosignificantlyincreaselevelofhemostaticfactors

    Markersofactivationofcoagulation

    CON Microthrombi arefoundinonly2%oftissuesfrompatientswhodieofliverdis.

    Fibrinogenturnoverisfromextravascularaccumulation

  • DICwithLiverDiseaseCurrentthinking DICisrareinliverdisease Patients withliverdiseasearesensitivetotriggersofDIC Syntheticcapacity Inabilitytoclearactivatedclottingfactors

  • LaboratoryFindingsinDIC LowPLT

    80%insurgicalortraumapatients

    95% FactorVIII mostlyelevatedduetomassivereleaseofvWF fromendotheliumandasacutephaseprotein

  • LaboratoryFindingsinDICFibrinogenconcentration Fib.isanacutephaseproteinwithinflammation

    Thus,Fib.levelmayremainnormalforalongtimedespiteongoingconsumption

    SensitivityoflowFib.forDx ofDICwas28% Hypofibrinogenemia onlyfoundinsevereDIC

  • LaboratoryFindingsinDICMarkersoffibringenerationanddegradation Ddimer sensitivebutnotspecific Fibrin(ogen)degradationproduct(FDP)metabolizedinliverandclearedbykidney

    Solublefibrinorfibrinmonomertheoreticallyuseful,butnoreliablequantitativetest

  • LaboratoryFindingsinDICEndogenouscoagulationinhibitors ProteinC,Antithrombin

    Reducedlevelsin90%ofDICpatients Predictorofpooroutcomeandmortality

  • LaboratoryFindingsinDICFibrinolyticmarkers Increasedfibrinolyticactivity

    Plasmaplasminogenand2antiplasmin:lowlevelsmayindicateconsumption

    Plasmin 2antiplasmin(PAP)complexes:increased

    PAI1:oftenelevatedandcorrelatewithunfavorableoutcome

  • LaboratoryFindingsinDICPointofcaretests Thromboelastography (TEG),ROTEM

    Usewholeblood globalassessmentofPLTfunction,coagulation,andfibrinolysis

    Correlatewithmorbidityandmortality Maybeoverlysensitivetofibrinogenadministration

  • DiagnosticAlgorithmforDx ofOvertDIC

    0 1 2 3Plateletcount,x109/L

    >100 100 5overtDIC,

  • DICScoringSystemsISTH JMHW JAAM CDSS

    Underlyingcondition

    Essential 01point Essential 0 2points

    Clinicalsymptom

    Bleed,organfailure

    SIRS Bleed,organdysfunction,microcirculatorydisorder

    PLT 0 2 0 3 0 2 0 2FDP,Ddimer 0 3 0 3 0 3 0 3Fibrinogen 0 1 0 2 0 1PT 0 2 0 2 0 1 PTor APTT:0 2Dx,points >5 >7 >4 >6 or7

    JMHW,JapaneseMinistryofHealthandwelfare;JAAM,JapaneseAssociationforAcuteMedicineCDSS,ChineseDICScoringSystem

  • DICScore ISTH:Sensitivity93%,Specificity98% Relatedtothemortality inpatientswithsepsis. Japanese scoringsystem

    Slightlyhighersensitivity,probablyfromdifferentpopulation(morehematologicmalignancies)

    SimplifiedJSTHDICforSepsis:withAntithrombinactivityinscore sens. 80%,spec.34%

    PregnancymodifiedISTHscoreofErez,Clark:needmorestudy

  • TreatmentofDICSPECIFIC Sepsis:antibiotics,pusdrainage Cancer:surgery,chemotherapy Abruptio placentae:uterusevacuation Aorticaneurysm:resection Trauma:debridementofcrushedtissue

  • TreatmentofDICSUPPORTIVE Transfusion ifbleeding,requiringinvasiveprocedure,atriskforbleeding

  • TreatmentofDICSUPPORTIVE Transfusion Heparin:purpurafulminans,beforesurgeryinchronicDIC(e.g.Aorticaneurysm),digitalgangrene,failureofintensivetransfusiontoimproveexcessivebleeding

  • TreatmentofDICSUPPORTIVE Transfusion Heparin Tranexamicacid inselectedcaseswithrefractorybleedingfromprimaryhyperfibrinolysis e.g.metastaticCAprostate,APL,giantcavernoushemangioma,heatstroke,acutecoagulopathyoftrauma,massivepostpartumhemorrhage

  • TypesofDICFibrinolysis

    Microthrombi

    Bleeding MassiveBleed/Consumptive

    Organfailure

    Asymptomatic

    WadaH,etal.JIntensiveCare2014;2:15

    APL,metastaticCAprostate,AAA,Earlytrauma

    SepsisCApancreas

    Postpartum,etc.

  • CriteriaforDx ofDICwithEnhancedFibrinolysis

    1. Prerequisite:TAT>20ug/LandPIC>10ug/L2. Labfindings atleast2offollowings:

    1. FDP>80ug/mL2. Fibrinogen

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