Response to antiplatelet therapy is independent of endogenous thrombin generation potential

Abstract

Background: Thrombin 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 methods: Thrombin 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.

Results: Peak 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.

Conclusion: Response to antiplatelet therapy with aspirin and clopidogrel is not associated with thrombin generation potential.

Keywords: AA; ACS; ADP; ARU; AU; AUC; HRPR AA; HRPR ADP; LTA; MEA; MFI; P2Y12 Reaction Units; PAR; PCI; PRI; PRU; Thrombin generation; VASP; VTE; acute coronary syndrome; adenosine diphosphate; aggregation units; angioplasty; antiplatelet therapy; arachidonic acid; area under the curve; aspirin reaction units; high on-treatment residual AA inducible platelet reactivity; high on-treatment residual ADP inducible platelet reactivity; light transmission aggregometry; mean fluorescence intensity; multiple electrode platelet aggregometry; percutaneous coronary intervention; platelet reactivity; platelet reactivity index; protease-activated receptor; vasodilator-stimulated phosphoprotein; venous thromboembolism.