Response to antiplatelet therapy is independent of endogenous thrombin generation potential |
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| Authors: | Thomas Gremmel Simon Panzer Sabine Steiner Daniela Seidinger Renate Koppensteiner Ingrid Pabinger Christoph W. Kopp Cihan Ay |
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| Affiliation: | 1. Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria;2. Department for Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria;3. Clinical Division of Haematology and Haemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria |
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| Abstract: | BackgroundThrombin is the most potent platelet activator, and achieves rapid platelet activation even in the presence of antiplatelet therapy. Since activated platelets respond stronger to additional stimuli, the extent of endogenous thrombin generation may in part be responsible for the reported response variability to aspirin and clopidogrel therapy.Patients and methodsThrombin generation potential was measured with a commercially available assay, and platelet reactivity was assessed with the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, light transmission aggregometry (LTA), the VerifyNow aspirin and P2Y12 assays, and multiple electrode aggregometry (MEA) in 316 patients on dual antiplatelet therapy undergoing angioplasty and stenting.ResultsPeak thrombin, the lag phase and the area under the curve of thrombin generation correlated poorly with on-treatment platelet reactivity by all test systems. High on-treatment residual platelet reactivity (HRPR) in response to arachidonic acid was seen in 33 (10.5%), 41 (13%), and 79 (25.7%) patients by LTA, the VerifyNow aspirin assay, and MEA, respectively. HRPR in response to adenosine diphosphate was seen in 150 (48.1%), 48 (15.3%), 106 (33.7%), and 118 (38.3%) patients by the VASP assay, LTA, the VerifyNow P2Y12 assay, and MEA, respectively. Peak thrombin generation did not differ between patients without and with HRPR by the VASP assay, LTA, the VerifyNow P2Y12 assay and MEA. In the VerifyNow aspirin assay, patients without HRPR had higher peak thrombin generation than patients with HRPR (p = 0.01). Finally, patients without and with high peak thrombin generation exhibited similar on-treatment platelet reactivity by all test systems, and high peak thrombin generation occurred to a similar extent in patients without and with HRPR.ConclusionResponse to antiplatelet therapy with aspirin and clopidogrel is not associated with thrombin generation potential. |
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| Keywords: | AA, arachidonic acid ADP, adenosine diphosphate HRPR AA, high on-treatment residual AA inducible platelet reactivity HRPR ADP, high on-treatment residual ADP inducible platelet reactivity PCI, percutaneous coronary intervention PAR, protease-activated receptor VTE, venous thromboembolism VASP, vasodilator-stimulated phosphoprotein LTA, light transmission aggregometry MEA, multiple electrode platelet aggregometry PRI, platelet reactivity index MFI, mean fluorescence intensity ARU, aspirin reaction units PRU, P2Y12 Reaction Units AU, aggregation units AUC, area under the curve ACS, acute coronary syndrome |
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