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Testsofcoagulation: Thrombintime TT ReagentsUsed Bovine/human thrombin Citratedplasma Tissuethromboplastin (TF) Ca++ Citratedplasma Phospholipid Surfaceactivator Ca++ Citratedplasma Measureseparatelyas detectorsforabove testscandetectsmall amountsoffibrin Factorsmeasured Fibrinogendeficiencyor thrombininhibition Normaltime 2025s 1112s INR=PTpatient PTnormal "therapeutic"INRforpts onoralanticoagulants= 23 Abnormalitiesindicated DIC Heparintherapy Renalandliverdz dysfibrinogenemias LiverDz Warfarintherapy DIC Hemophilia Christmasdz LiverDz Warfarintherapy DIC DIC Liverdisease hereditary hypofibrinogenemia NOTVitKdeficiency
PT
Prothrombin timePT
Deficiencyorinhibition of:VII,X,V,II,fibrinogen
aPTT
30s
Fibrinogen concentration
Fibrinogen
normalfibrinogenconc= 200400mg/dL
Afterextendedclottingtimedo50:50test Mixnormalplasmawithpatientsplasma Ifincreasedtimenormalizesproblemwasdeficiency Ifincreasedtimeremains,problemisaninhibitorofcoagulation Whatlevelofdeficiencywillcauseabnormaltesttimesandwhatwillmakeyoubleed? <40%ofnormalclottingfactorlevelswillleadtoabnormalPTandPTT <30%ofnormallevelswithproduceexcessivebleeding Clottingsystemworksdifferently"invivo" Invivo,tissuefactorVIIaactivatesfactorIXtoXIa,andinthepresenceoffactor VIII,isabletoactivatefactorXtoXa. Inthetesttube,theintrinsicandextrinsicsystemsareindependentofone
2.
3.
NormalPTbutaPTT. DefectiveclottingfactorsmustincludefactorsXII,XI,IXorVIII FactorXIIdeficiencygreatlyprolongsaPTT,butnota/wbleeding FactorsVIIIdeficiencyhemophiliaA FactorIXdeficiencyhemophiliaB PTandaPTT Either1clottingfactordeficiencyin"commonpathway"ormultipleclotting factordeficienciesinbothpathways Inheriteddisordermostlikelythatasingleclottingfactordeficiencyisthe problem(e.g.,factorXorfactorVdeficiency) Usuallymultipleclottingfactordeficiencies CausesvitaminKdeficiency,liverdisease,orDIC.
another;i.e.,tissuefactorVIIaactivatesfactorXtoXadirectly
DisseminatedIntravascularCoagulation(DIC)activationofthecoagulationsystem (thrombingeneration)invivowithinthevascularsystem. Factorsare"consumed"inreaction:fibrinogen,factorsVandfactorVIII Plateletsmayalsobeconsumedviathrombinmediatedplateletaggregation,or depositioninmicrocirculation Fibrindegradationproducts(Ddimer)aregeneratedbytheactionofplasminon fibrin. CanalsoprolongTTandinterferew/plateletfunction TypicalDICLabs: PT24seconds(normal1113seconds) aPTT65seconds(normal2535seconds) Thrombintime35seconds(normal2030seconds) Fibrinogenconcentration40mg/dL(normal200400mg/dL) Plateletcount50,000/cmm(normal200400,000/cmm Bleedingtime18minutes(normal<10minutes) Ddimer16g/mL(normal<0.25g/mL) TheLupusAnticoagulant=antiphospholipidantibodyinterferesw/bindingofclotting factorstophospholipidsurfaces. ScreeningteststhatdependonphospholipidareprolongedespaPTT (sometimesPT,butnotTT) Mixingstudieswillnotcorrectindicatinganinhibitor,becausethelupus anticoagulantalsoeffectsbindingofnrlclottingfactors Lupusanticoagulantsdonotcausebleeding (despiteaPTT)maybea/w thrombosis! ClottingFactorAssays MeaureclottingfactoractivityviaaPTTorPT Testsystemusessequentialknownfactordeficientplasmawhichisaddedtothe patientsplasma Thetestisthensensitiveonlytosinglefactordepletion. ScreeningTestsofHemostaticPlugFormation Plateletcountmeasuresthenumberofplatelets Ivybleedingtime/PFA100measureplateletfunction PFA100 =invitroplateletfunctiontestlargelyreplacedbleedingtimeinmany places o Citratedwholebloodisforcedacrossacollagenimpregnatedgridathigh shearinthepresenceofeitherepinephrineorADP. o Maydetectplateletfunctiondefects,butunclearifaccuratelypredicts futurebleeding Componentsofplateletfunctionmeasured: o PlateletadhesiontocollagenvonWFandglycoproteinIb(orGPI) o Releasereaction(ADP,TXA2) o Plateletaggregation(fibrinogen,GPIIb/IIIa).