止血障礙-血栓形成課件

止血障礙：血栓形成DisordersofHemostasis:Thrombosis止血障礙：血栓形成止血障礙：血栓形成HypercoagulabilityDefinition:Alterationinthehemostaticbalancebetweenbloodfluidityandclotformation.Thisisduetogeneticandacquireddisorderswhichshiftthisbalancetowardexcessiveorinappropriateplateletaggregationandfibrinformationandpredisposetothrombosis.止血障礙：血栓形成PrethromboticStates10-inheritedabnormalitiesresultingfrommutationsaffectingthefunctionofcoagulantproteinsandnaturalinhibitors20-acquireddefectsthateitheraffecttheendothelium,fluidfloworbloodcomponents.Thesedefectsareoftensuperimposedon10defects止血障礙：血栓形成Hypercoagulability:

PrethromboticStatesVirchow(1856)AbnormalitiesofbloodvesselsAbnormalitiesoffluidflowAbnormalitiesofbloodcomponents止血障礙：血栓形成BloodVesselAbnormalitiesEndothelialcellantithromboticproperties-PGI2,NO2,TFPI,PAI-1,heparans,thrombomodulinGeneticpredispositionandacquireddefectsinthesefunctionsincreasetheriskofarterialandvenousthrombosisRoleofdietaryexcesses,hypertension,diabetesmellitus,obesity,smoking,lipidabnormalitiesinatherosclerosis止血障礙：血栓形成AtherosclerosisEndothelialinjuryanddysfunctionLDLcholesterol–oxidizedLDL---foamcellsDiabetesmellitus–glycatedLDLcholesterolSmoking–freeradicalproductionHypertension–smoothmuscleproliferationGeneticalterations–MTHFRmutations止血障礙：血栓形成R.Ross.Atherosclerosis.NEJM340:115-126,1999止血障礙：血栓形成AtherosclerosisSitespecific:BifurcationsBranchingvesselsCurvaturesDecreasedshearstressandincreasedturbulencePlaqueformationandrupture止血障礙：血栓形成Unstableplaque.R.RossNEJM340:115-126,1999.止血障礙：血栓形成BloodFlowAbnormalitiesStasisistheunderlyingmechanismasthecauseofvenousorarterialthrombosisConditions-immobilization,surgery,congestiveheartfailure,pregnancy,obesity.IncreasedbloodviscosityRBCs-polycythemias,sicklecellsWBCs–myeloproliferativedisordersespeciallyCMLPlatelets-primarythrombocytosisParaproteins-Myeloma,Waldenstrom’sMacroglobulinemia止血障礙：血栓形成Hypercoagualbility:

Hereditary/AcquiredFactorVLeidenProthrombin20210ProteinCProteinSAnti-thrombinIIIDysfibrinogenemiaHyperhomocysteinemiaPAI-IPlateletglycoproteinIIb/IIIa止血障礙：血栓形成止血障礙：血栓形成FactorVLeidenMutationatposition506renderingFVinsensitivetodegradationbyactivatedproteinC.Autosomaldominant;5%Caucasianpopulation.Heterozygote-7xincreasedriskforvenousthrombosisHomozygote-80xincreasedriskOftenfoundinassociationwithotherriskfactors-proteinCandSdeficiencies止血障礙：血栓形成Prothrombin20210MutationMutationresultsinincreasedsynthesisofprothrombinresultinginelevatedplasmalevelsofbiochemicallynormalprothrombinAutosomaldominant;1-2%ofpopulationIncreasedriskofvenousthrombosis-2x止血障礙：血栓形成ProteinCDeficiencyAutosomaldominantMutationresultsinmildtoseveredeficiency;increaseriskforvenousthrombosishomozygote=purpurafulminans0.2%ofUSpopulationAcquired-DIC,liverdisease,oralcontraceptives,oralanticoagulantuse止血障礙：血栓形成ProteinSDeficiencyAutosomaldominantIncreasedriskofvenousthrombosisAcquireddeficiencies-DIC,liverdisease.coumarintherapy,pregnancy(2ndand3rdtrimesters),estrogenreplacementtherapy,L-asparginasechemotherapy止血障礙：血栓形成HyperhomocysteinemiaIncreasedlevelsareassociatedwithincreasedriskofarterialandvenousthrombosis.Multipleeffectsonendothelialcells-decreasedthrombomodulin,increasedTFactivity,inhibitionofNOandTPA止血障礙：血栓形成HyperhomocysteinemiaPrimary-mutationofMTHFRgeneAcquired-vitaminB12,B6orfolicaciddeficiency,hypothyroidism,isoniazid,methotrexate,theophylline止血障礙：血栓形成HereditaryThrombophiliaConsiderif:familyhistoryofthrombosishistoryofrecurrentthrombosisthrombosisatayoungagenoacquiredpredisposingfactorsforthrombosis止血障礙：血栓形成MalignancyRiskforthrombosisismultifactorial.Predominantlyvenousthrombosis-stasis,tumorinvasionofvessels,chemotherapyeffectssuperimposedonacquiredorprimarydefectsinhemostasis.Distinctprocoagulant(cysteineprotease)foundinmanypatientswhichcanactivateFXdirectly.止血障礙：血栓形成AntiphospholipidAntibodySyndromeAutoimmunedisorder,eitherprimaryorsecondary,associatedwithanincreasedriskforarterialandvenousthrombosis.AntibodyistocardiolipininAPA(ELISAassay);antibodyistobeta2glycoprotein1andplateletphospholipidsinpatientswithlupusanticoagulants(aPTTand/orPT).止血障礙：血栓形成ThrombusSize,shapeandmorphology

Muralthrombus Infectedthrombus–bacterialendocarditis Verrucousthrombus–Libman-Sacks endocarditis止血障礙：血栓形成止血障礙：血栓形成止血障礙：血栓形成止血障礙：血栓形成ThrombusNaturalhistory:ResolutionPropagationFragmentation/embolizationOrganization止血障礙：血栓形成Resolution止血障礙：血栓形成Propagation–completeocclusion止血障礙：血栓形成FFragmentationandEmbolization 止血障礙：血栓形成Organization–Fibroblastproliferation止血障礙：血栓形成Organization–Endothelialcelldifferentiation止血障礙：血栓形成Resolution止血障礙：血栓形成Organization-Rethr