1、lDaniel I.Simon,M.D.lAssociate Director,Interventional CardiologylBrigham and Womens HospitallAssociate Professor of MedicinelHarvard Medical SchoollBoston,MA USA2020年10月2日1lDoes a standardized definition exist?lAre there reliable tests to diagnose this phenomenon?lWhat are the possible mechanisms a
2、nd future implications?lDoes it have any clinical significance?lHow do we manage patients with Aspirin resistance?2020年10月2日2Harrison P.Br J Hematology 2000;111:733-744Platelet Function TestBleeding timeAggregometry-turbidometric methodsAggregometry-impedance methodsAggregometry&luminescenceAdenine
3、nucleotidesThromboelastography(TEG)Glass filterometerPlatelet release markersIn Vivo screening testResponsiveness to panel agonistsResponsiveness to panel agonistsCombined aggregation and ADP releaseStored and released ADPGlobal HemostasisHigh shear platelet functionIn vivo platelet activation marke
4、rsAdvantagesPhysiological DiagnosticWhole blood testMore informationSensitivePredicts bleedingSimpleSimple,systemic measure of platelet activationDisadvantagesInsensitive,invasive&high variabilityLabor intensive&non-physiologicalInsensitive Semi-quantitative Specialized equipmentMeasures clot proper
5、ties only,insensitive to ASARequires blood counterProne to artifact2020年10月2日3(PFA)-100 Whole blood+Primary Limited range-most ptshemostasis after GP IIb/IIIa inhibitors have (high shear closure times 300 sec,so may adhes/aggreg)not be able to discern diff.Used to assay ADP antagonist Clot Signature
6、 Whole blood +Adhesion,Large instrument for routine useAnalyzeraggregation and interpretation of results is complexRapid platelet Whole blood +Aggregation GP IIb/IIa:baseline sample req.function assay Clinical outcome data(GOLD)Aspirin:AA-like agonistHarrison P.Br J Hematology 2000;111:733-744Mukher
7、jee D&Moliterno DJ.Clin Pharmacokinet 2000;39(6):445-458Flow cytometry Whole blood -Platelet GP,Flexible&powerful.Requires activation markers,specialized operator.ExpensivePlatelet function2020年10月2日4Gum PA et al.Am J Cardiol 2001;88:230-2352020年10月2日5Wang JC et al.Amer J Cardiol 2003;92:1492-4l23.4
8、%Aspirin non-responsivelAccumetrics VerifyNow AspirinlDefinition:ARU 550lMultivariate analysis:history of CAD associated with twice the odds of being ASA non-responder(odds ratio 2.09,95%CI 1.189-3.411,p=0.009)lNo association with gender,DM,smoking,ASA dose2020年10月2日62020年10月2日7Stroke1 1500 mg Plt R
9、eactivity 24 mStroke/MI/10-fold lower (n=180)Vascular death risk in ASA respondersPVD2 100 mg Whole blood 18 m Arterial 87%higher risk(n=100)aggregometry Occlusion in ASA-R CVD/CVA3 100 mg PFA-1060 mRecurrent CVA/Recurrent CVA 34%(n=53)TIA TIA ASA-R vs.0%no recurrent eventsSubgroup 75-325 mg Urinary
10、 11-dehydro 5 yrs MI/Stroke/1.8 times HOPE4 TX B2 CVDeath higher risk in (n=967)upper vs.lower quartileCVD5 325 mg Optical platelet 679185 Death/MI/CVA 24%ASA-R vs.(n=326)aggregation days 10%ASA-S HR 3.12(95%CI 1.1-8.9,p=0.03)1.Grotemeyer KH,et al.Thromb Res 1993;71:397-4032.Mueller MR,et al.Thromb
11、Haemost 1997;78:1003-10073.Grundmann K,et al.J Neurol 2003;250:63-664.Eikelboom JW,et al.Circulation 2002;105:1650-16555.Gum PA,et al.J Am Coll Cardiol 2003;41:961-965 2020年10月2日8Eikelboom JW,et al.Circulation 2002;105:1650-16552020年10月2日9Gum PA,et al.J Am Coll Cardiol 2003;41:961-965 ASA-R:mean agg
12、regation 70%with 10 M ADP&20%with 0.5 mg/ml AAp=0.032020年10月2日10Mueller MR et al.Thromb Haemost 1997;78:1003-10072020年10月2日11Grotemeyer KH et al.Thromb Res 1993;71:397-4032020年10月2日12Grundmann K et al.J Neurol 2003;250:63-6653 CVA pts on ASA 100 mg for secondary prevention 60 months 2020年10月2日13Chen
13、 et al.J Amer Coll Cardiol 2004;43:1122-6RPFA-ASA,ASA/clopidogrel(n=151),19.2%ASA resistant2020年10月2日14AspirinGp IIb/IIIaADP=adenosine diphosphate,TXA2=thromboxane A2,COX=cyclooxygenase.Schafer AI.Am J Med 1996;101:199209.2020年10月2日15The CURE Trial Investigators.N Engl J Med.2001;345:494-502.2020年10
14、月2日16*In combination with standard therapyThe CURE Trial Investigators.N Engl J Med.2001;345:494-502.2020年10月2日17PCI30 days post PCIEnd of follow-upUp to 12 monthsafter randomizationN=13452020年10月2日18Steinhubl et al.JAMA 200226.9%relative risk reduction(CI 3.9-44.4%;P=0.02)Absolute reduction=3%2020年
15、10月2日19 lEliminate interfering substances(ibuprofen)l Increase aspirin dosel Use other anti-platelet medications such as clopidogrel to prevent recurrent ischemic eventsl Educate patient on importance of compliance2020年10月2日20演讲完毕，谢谢观看！Thank you for reading!In order to facilitate learning and use,the content of this document can be modified,adjusted and printed at will after downloading.Welcome to download!汇报人：XXX 汇报日期：20XX年10月10日21
