LOGO缺血性脑卒中抗凝治疗进展——直接凝血酶抑制剂的崛起血栓形成机制示意图缺血性卒中抗栓的特异性治疗抗凝溶栓抗血小板急性脑梗死抗凝治疗的作用机制预防早期卒中复发(再血栓栓塞)阻止神经症状的恶化(防止血栓延长)改善卒中预后(改善微循环和血供)抗凝药物的作用靶点及发展历史2008年p.oⅡa和Ⅹa因子抑制剂2002年磺达肝素iv（ATⅢ+Ⅹa）1990年阿加曲班iv（Ⅱa）1980年低分子肝素ih（ATⅢ+Ⅹa+Ⅱa）1940年华法令p.o(Ⅱ,Ⅶ,Ⅸ,Ⅹ,C,S)1935年普通肝素iv（ATⅢ+Ⅹa+Ⅱa）多靶点向单一靶点发展抗凝药物的分类进入美国新版指南进入美国新版指南2013年美国AHA/（ASA）最新急性缺血性卒中早期管理指南2007年2013年Stroke.publishedonlineJanuary31,2013;美国指南有关抗凝药物治疗的新推荐Atpresent,theusefulnessofargatrobanorotherthrombininhibitorsfortreatmentofpatientswithacuteischemicstrokeisnotwellestablished.Theseagentsshouldbeusedinthesettingofclinicaltrials.TheusefulnessofurgentanticoagulationinpatientswithseverestenosisofaninternalcarotidarteryipsilateraltoanischemicstrokeisnotwellestablishedIIb/BNEWIIb/BNEWStroke.publishedonlineJanuary31,2013;美国指南对直接凝血酶抑制剂的背景评论Directthrombininhibitorsmaybeusefulinacuteischemicstrokebecauseoftheiractionsthatlimitthrombosis.Thesemedicationscouldbeconsideredasanalternativetoanticoagulants,andtheycouldbeadministeredtothosepeoplewhodevelopheparin-associatedthrombocytopenia.Stroke.publishedonlineJanuary31,2013;首次将直接凝血酶抑制剂（阿加曲班、达比加群）写入美国指南，以区分传统的间接凝血酶抑制剂（肝素、低分子肝素）。单独对直接凝血酶抑制剂进行了介绍，并有新的推荐意见。美国指南对达比加群的背景介绍Dabigatran,adirectthrombininhibitor,hasbeenevaluatedoverthepastdecadeforthepreventionofthromboemboliceventsinpatientsafterorthopedicprocedures.Morerecently,intheRE-LYstudy(RandomizedEvaluationofLong-termAnticoagulationTherapy),dabigatrandemonstratedbenefitcomparedwithwarfarinforthepreventionofstrokeorsystemicembolizationinpatientswithatrialfibrillation.Atlowerdoses,dabigatranwasnoninferiortowarfarinwhiledemonstratingfewerhemorrhagiccomplications.Athigherdoses,dabigatranwasmoreeffectivethanwarfarinbuthadsimilarbleedingrisk.InOctober2010,theFDAapprovedthehigher150-mgtwice-a-daydoseforstrokepreventioninpatientswithatrialfibrilla-tion.Forpatientswithimpairedrenalfunction,alower75-mgtwice-a-daydoseisrecommended.Stroke.publishedonlineJanuary31,2013;美国指南对阿加曲班的背景介绍Adose-escalationstudyofargatroban,alsoadirectthrombininhibitor,foundthatitprolongedaPTTlevelsbutdidnotincreasemortalityortheriskofseriousbleeding.AJapanesestudyretrospectivelyexaminedtheimpactofargatrobanonoutcomesamongpatientswithcardioembolicstroke.Itconcludedthatargatrobanmaybesuperiortoheparininreducingmortalityandimprovingoutcomesafterstrokes.Asinglecaseinwhichargatrobanwassuccessfullyadministeredinadditiontointravenousandintraarterialfibrinolysiswasalsoreported.Additionalresearchisongoingregardingtheroleofargatrobaninthetreatmentofpatientswithacutestroke.Stroke.publishedonlineJanuary31,2013;直接凝血酶抑制剂的药理作用机制直接凝血酶抑制剂：阿加曲班、达比加群等间接凝血酶抑制剂：肝素/低分子肝素等NEnglJMed2005;353:1028-40AdvantageMechanismAdvantageMechanismBettersuppressionofthrombusInhibitfreeandboundgrowththrombinRetainactivityinpresenceDonotbindPF4orvWFofplatelet-richthrombiPredictableanticoagulantDonotbindplasmaproteinsresponseNoriskofHITDonotbindPF4BettersuppressionofthrombusInhibitfreeandbound...
