1、lDoes a standardized definition exist?lAre there reliable tests to diagnose this phenomenon?lWhat are the possible mechanisms and future implications?lDoes it have any clinical significance?lHow do we manage patients with Aspirin resistance?Harrison P.Br J Hematology 2000;111:733-744Platelet Functio
2、n TestBleeding timeAggregometry-turbidometric methodsAggregometry-impedance methodsAggregometry&luminescenceAdenine nucleotidesThromboelastography(TEG)Glass filterometerPlatelet release markersIn Vivo screening testResponsiveness to panel agonistsResponsiveness to panel agonistsCombined aggregation
3、and ADP releaseStored and released ADPGlobal HemostasisHigh shear platelet functionIn vivo platelet activation markersAdvantagesPhysiological DiagnosticWhole blood testMore informationSensitivePredicts bleedingSimpleSimple,systemic measure of platelet activationDisadvantagesInsensitive,invasive&high
4、 variabilityLabor intensive&non-physiologicalInsensitive Semi-quantitative Specialized equipmentMeasures clot properties only,insensitive to ASARequires blood counterProne to artifact(PFA)-100 Whole blood+Primary Limited range-most ptshemostasis after GP IIb/IIIa inhibitors have (high shear closure
5、times 300 sec,so may adhes/aggreg)not be able to discern diff.Used to assay ADP antagonist Clot Signature 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
6、assay Clinical outcome data(GOLD)Aspirin:AA-like agonistHarrison P.Br J Hematology 2000;111:733-744Mukherjee D&Moliterno DJ.Clin Pharmacokinet 2000;39(6):445-458Flow cytometry Whole blood -Platelet GP,Flexible&powerful.Requires activation markers,specialized operator.ExpensivePlatelet functionGum PA
7、 et al.Am J Cardiol 2001;88:230-235Wang JC et al.Amer J Cardiol 2003;92:1492-4l23.4%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 ass
8、ociation with gender,DM,smoking,ASA doseStroke1 1500 mg Plt Reactivity 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
9、 TIA ASA-R vs.0%no recurrent eventsSubgroup 75-325 mg Urinary 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
10、KH,et al.Thromb Res 1993;71:397-4032.Mueller MR,et al.Thromb 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 Eikelboom JW,et al.Circulation 2002;105:1650-1655Gum PA,et al.J Am Coll
11、 Cardiol 2003;41:961-965 ASA-R:mean aggregation 70%with 10 M ADP&20%with 0.5 mg/ml AAp=0.03Mueller MR et al.Thromb Haemost 1997;78:1003-1007Grotemeyer KH et al.Thromb Res 1993;71:397-403Grundmann K et al.J Neurol 2003;250:63-6653 CVA pts on ASA 100 mg for secondary prevention 60 months Chen et al.J
12、Amer Coll Cardiol 2004;43:1122-6RPFA-ASA,ASA/clopidogrel(n=151),19.2%ASA resistantAspirinGp IIb/IIIaADP=adenosine diphosphate,TXA2=thromboxane A2,COX=cyclooxygenase.Schafer AI.Am J Med 1996;101:199209.The CURE Trial Investigators.N Engl J Med.2001;345:494-502.*In combination with standard therapyThe
13、 CURE Trial Investigators.N Engl J Med.2001;345:494-502.PCI30 days post PCIEnd of follow-upUp to 12 monthsafter randomizationN=1345Steinhubl et al.JAMA 200226.9%relative risk reduction(CI 3.9-44.4%;P=0.02)Absolute reduction=3%lEliminate interfering substances(ibuprofen)l Increase aspirin dosel Use o
14、ther anti-platelet medications such as clopidogrel to prevent recurrent ischemic eventsl Educate patient on importance of compliancelASA use associated with 23%reduction in the odds of vascular eventslBeneficial anti-thrombotic effect of ASA mediated by irreversible acetylation of COX-1lASA resistance 5-60%lASA resistance associated with increased risk of major adverse cardiovascular events
