批发和零售贸易零售业

Hemostasis/CoagulationGregoryS.Travlos,DVM,DACVPNationalInstituteofEnvironmentalHealthSciencesResearchTrianglePark,[e-mail]销售信•ItisaseriesofphysiologicalandbiochemicaleventswhichterminateintheformationofaninsolublefibrinclotHemostaticSequence:•Interactionbetweenvesselwallandplatelets•Bloodcoagulation•FibrinolysisHemostaticComponentInteractionsThompson&Harker,1983BloodVesselsIntactendotheliumformsathromboresistantsurface•Requiredforthefreeflowofblood;doesnotpromoteplateletadherenceoractivatecoagulation•Passivemechanisms:•Endothelialglycocalyx(negativecharge-repelslike-chargedparticles,e.g.,platelets).•Presenceofa2-macroglobulinatcellsurface(proteaseinhibitor).•Activemechanisms:•Endothelialcellsremoveplateletaggregationpromotersfromcirculation(e.g.,PGF1,bradykinin,serotonin,adeninenucleotides).•SecretionofPGI2-potentinhibitorofplateletaggregation,inducesvasodilation.Proteoglycanmatrixofthevesselwallinfluencesthrombogenicity.•Heparin,heparansulfateanddermatansulfatehaveanticoagulantactivity;otherglycosaminoglycansandhyaluronicaciddonot.•Veinshavethehighestconcentration.EndotheliumBesidestheirroleinthromboresistance,endothelialcellshaveadditionalsyntheticfunctions.•ProduceVonWillebrand’sfactor•Absorbedbyplatelets;neededforadherencetocollagen•Produceplasminogenactivator(tPA)•Mediatesfibinolysis•Injuredcellsreleasethromboplastin(factorIII)•Activatesthe“extrinsic”coagulationcascade•Others(e.g.,typeIIIandIVcollagens,elastin,fibronectin,etc.)BloodVesselStructureThompson&Harker,1983PlateletsAdheretoexposedcollagen(plateletplug)•Occursinseconds;cancontrolhemorrhageofminuteinjuriesSecretoryfunctions;mediatorsofcoagulationandfibrinolysis•ReleasesADP;stickyandpromotesplateletadherence•ADPactivatesphospholipaseA2whichstimulatesthromboxaneA2synthesis•Releaseofmembranefibrinogen,factorV,factorVIIIandcalcium•Releaseofmembraneplateletphospholipid.Platelet-TEMmitochodrionmicrotublulesOCSgranulesUltrastructuralandFunctionalPlateletAnatomyPlatelets-cont.Theroleofplateletsinhemostasisisasimportantasthecoagulationmechanism.•Thrombocytopenia,thrombastheniaorthromobopathia-impairhemostasis•Thrombocytosisorthrombocythemia-mayimpair,butusuallypromotesclotting(predisposestothrombosis).Plateletspromotehemostasisby:•ReleaseofADPandotheragonists;promotesadherence.•ADPactivatesphospholipaseA2whichstimulatesthromboxaneA2synthesis•ThromboxaneA2-stimulatesvasoconstrictionandplateletaggregation•Releaseofmembranefibrinogen,factorV,factorVIIIandcalcium•Componentsofcoagulationlocalizedatsiteofinjury•Releaseofmembraneplateletphospholipid.•Acceleratesthe“intrinsic”and“common”pathwaysofcoagulationProstaglandinMetabolismHarlan&Harker,1981HemostaticPlateletFunctionsThompson&Harker,1983PlateletResponseWhenavesselisinjuredorseveredabrief,local,reflexvasoconstrictionoccurs.•Reducesbloodflowatsite.•Maintainedbyvasoactivecompounds(platelets,surroundingtissues).Passingplateletsadheretoexposedcollagen.•Occursinseconds;initiallyadhereinasinglelayerandbecomeactivated.•Severeinjury-collagenservesasapotentplateletactivator.•Lesssevereinjury-vWFandfibrinogenbecomethemajoractivators.Theadheredplateletsundergoaconformationalchange.•Fromdiscoidtodevelopmentoflongfilopodia.•ActivationofGPreceptorsforfibrinogenand/orvWF(GPIIb/IIIaandGPIb/IX/V).StructureoftheGPIb-IX-VreceptorTablin,2000PlateletResponsetoAgonistsPlatelets-unstimulatedAdditionofADP(mildstimulation)Additionofthrombin(strongstimulation)CharacteristicdiscoidshapeShapechange(elongationandcrescents)andfilaformprocessformation(arrows)Increasedspreading,filaformprocessextension(arrows)andaggregateformation(stars)SEMplates;Gentry,2000PlateletResponsecont.Activatedplateletsreleasetheira-granuleanddensebodycontentsinducingadditionalplateletrecruitment.•Densegranules-ADP,serotoninandepinephrine.•alpha-granules-fibrinogen(andvWFinhumanandpig).•SynthesisandreleaseofPAFandTxA2.Theagonistsacceleratethedevelopmentofanirreversibleplateletaggregate(plateletplug).•Reversiblev.irreversibleresponses.•ThrombocytesofbirdsandreptilesdonotrespondtoADP.•Serotoninandepinephrine:•Serotonin-shapechange(rat,g.piganddog);aggregation(human,rabbit,cow,horse,pig,sheepandcat).•Epinephrine-onlyhuman,primate,catandhorseplateletsappearresponsive.•Eitherserotoninorepinephrinecombinedwithanotheragonist-strongresponseinallspecies.PlateletResponsecont.Moreaboutagonists.•PlateletActivatingFactor(PAF).•Cow,horse,sheep,primate,dog,g.pigandrabbitrespondtoPAF.•Humanlesssensitiveandratandmouseareinsensitivetothisagonist.•ThromboxaneA2(TxA2).•Strongagonist-human,g.pigandrabbit.•Weakagonist-horse.•Insensitive-rat,cow,pig.Inreallife,however,plateletsareexposedtomultipleagonistsfromplateletsandothercells(e.g.,redcells,ADP;whitecells,PAF).PlateletAggregationtoThrombinHarlan&Harker,1981HemostaticPlugFormationBaumgartner&Muggli,1980CoagulationSystemConsistsofacascadingsystemofproteins•Primarilyoriginatingfromliver(exceptfactorIII)•Circulateininactiveform(exc