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1、DisordersofHemostasis:ThrombosisJohnLazarchick,M.D.Director,Hematopathology/HemostasisAugust30,2001HypercoagulabilityDefinition:Alterationinthehemostaticbalancebetweenbloodfluidityandclotformation.Thisisduetogeneticandacquireddisorderswhichshiftthisbalancetowardex
2、cessiveorinappropriateplateletaggregationandfibrinformationandpredisposetothrombosis.PrethromboticStates10-inheritedabnormalitiesresultingfrommutationsaffectingthefunctionofcoagulantproteinsandnaturalinhibitors20-acquireddefectsthateitheraffecttheendothelium,fluid
3、floworbloodcomponents.Thesedefectsareoftensuperimposedon10defectsHypercoagulability: PrethromboticStatesVirchow(1856)AbnormalitiesofbloodvesselsAbnormalitiesoffluidflowAbnormalitiesofbloodcomponentsBloodVesselAbnormalitiesEndothelialcellantithromboticproperties-PG
4、I2,NO2,TFPI,PAI-1,heparans,thrombomodulinGeneticpredispositionandacquireddefectsinthesefunctionsincreasetheriskofarterialandvenousthrombosisRoleofdietaryexcesses,hypertension,diabetesmellitus,obesity,smoking,lipidabnormalitiesinatherosclerosisAtherosclerosisEndoth
5、elialinjuryanddysfunctionLDLcholesterol–oxidizedLDL---foamcellsDiabetesmellitus–glycatedLDLcholesterolSmoking–freeradicalproductionHypertension–smoothmuscleproliferationGeneticalterations–MTHFRmutationsR.Ross.Atherosclerosis.NEJM340:115-126,1999AtherosclerosisSite
6、specific:BifurcationsBranchingvesselsCurvaturesDecreasedshearstressandincreasedturbulencePlaqueformationandruptureUnstableplaque.R.RossNEJM340:115-126,1999.BloodFlowAbnormalitiesStasisistheunderlyingmechanismasthecauseofvenousorarterialthrombosisConditions-immobil
7、ization,surgery,congestiveheartfailure,pregnancy,obesity.IncreasedbloodviscosityRBCs-polycythemias,sicklecellsWBCs–myeloproliferativedisordersespeciallyCMLPlatelets-primarythrombocytosisParaproteins-Myeloma,Waldenstrom’sMacroglobulinemiaHypercoagualbility: Heredit
8、ary/AcquiredFactorVLeidenProthrombin20210ProteinCProteinSAnti-thrombinIIIDysfibrinogenemiaHyperhomocysteinemiaPAI-IPlateletglycoproteinIIb/IIIaFactorVLe
