Assessment of platelet‐derived thrombogenicity with the total thrombus‐formation analysis system in coronary artery disease patients receiving antiplatelet therapy

Abstract

Total thrombus‐formation analysis system (T‐TAS) quantitatively measures platelet thrombus formation. We examined the utility of T‐TAS in patients with coronary artery disease. T‐TAS can discriminate different types of the antiplatelet therapy in the same measuring method. Genetic background, cytochrome P‐450 2C19 genotypes, also influenced T‐TAS parameters. Summary BackgroundAccurate evaluation of thrombogenicity helps to prevent thrombosis and excessive bleeding. The total thrombus‐formation analysis system (T‐TAS) was developed for quantitative analysis of platelet thrombus formation by the use of microchips with thrombogenic surfaces (collagen, platelet chip [PL‐chip]; collagen plus tissue factor, atherome chip [AR‐chip]). We examined the utility of the T‐TAS in the assessment of the efficacy of antiplatelet therapy in patients with coronary artery disease (CAD). Methods and ResultsIn this cross‐sectional study, 372 consecutive patients admitted to the cardiovascular department were divided into three groups: patients not receiving any antiplatelet therapy (control, n = 56), patients receiving aspirin only (n = 69), and patients receiving aspirin and clopidogrel (n = 149). Blood samples were used for the T‐TAS to measure the platelet thrombus‐formation area under the curve (AUC) at various shear rates (1500 s−1 [PL18‐AUC10] and 2000 s−1 [PL24‐AUC10] for the PL‐chip; 300 s−1 [AR10‐AUC30] for the AR‐chip). The on‐clopidogrel platelet aggregation was measured by the use of P2Y12 reaction units (PRUs) with the VerifyNow system. The mean PL24‐AUC10 levels were 358 ± 111 (± standard deviation) (95% confidence interval [CI] 328.9–387.1) in the control group, 256 ± 108 (95% CI 230.5–281.5) in the aspirin group, and 113 ± 91 (95% CI 98.4–127.6) in the aspirin/clopidogrel group. In the aspirin/clopidogrel group, the PL24‐AUC10 was higher in poor metabolizers (PMs) with cytochrome P450 2C19(CYP2C19) polymorphisms (152 ± 112, 95% CI 103.4–200.6) than in the non‐PM group (87 ± 74, 95% CI 73.8–100.2). ConclusionsOur findings suggest that the PL24‐AUC10 level measured by the T‐TAS is a potentially suitable index for the assessment of antiplatelet therapy in CAD patients.

Total Thrombus-Formation Analysis System (T-TAS): Clinical Application of Quantitative Analysis of Thrombus Formation in Cardiovascular Disease

“…As shown in ►Table 3, in a report of Arima et al, samples from patients with cardiovascular disease taking no antiplatelet medication (controls), treated with aspirin, and treated with DAPT were comparatively analyzed with VerifyNow PRU and PL chip. 42 The PRU levels were lower in the aspirin/clopidogrel group than the control and aspirin groups, but there were no significant differences in PRU levels between the control and aspirin groups. On the other hand, the PL-AUC levels were significantly lower in the two antiplatelet therapy groups compared with the control group, and the level was significantly lower in the aspirin/ clopidogrel group than the aspirin group, which were mostly consistent with data from other clinical studies.…”

“…A previous study showed the significant positive correlation between PL 18 -AUC 10 and PL 24 -AUC 10 (or simply, PL-AUC) levels in samples from the patients with cardiovascular disease. 42 The AR chip is typically tested at a flow rate of 10 μL/min, defined as AR 10 -AUC 30 (or simply, AR-AUC), which corresponds to a shear rate of 600 s À1 . An in vitro diagnostic version of T-TAS has been developed that uses fixed flow rates of 18 and 10 μL/min for the PL and AR chips, respectively, and does not contain video capture capabilities.…”

In vitro studies show synergistic effects of a procoagulant bispecific antibody and bypassing agents

“…Additionally, plasma from a small number of patients was used in the study, which is mitigated by the wide range of plasma samples analyzed, covering a range of BU titers from 1 IU mL À1 to 133 IU mL À1 , achieving similar TG curves and responses to procoagulant stimuli. Although the T-TAS was previously utilized in studies on antiplatelet and antithrombotic therapies [28,29], the parameters used in our study were different, and thrombogenicity cannot be inferred on the basis of a direct comparison with published results. However, the T-TAS was mainly utilized to corroborate results from ROTEM and the TG assay [30], which, in turn, have been shown to correlate with thrombotic events in a variety of disease states [19,[31][32][33].…”

Total Thrombus‐formation Analysis System Predicts Periprocedural Bleeding Events in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention

“…Using this system, we reported previously the usefulness of the area under the flow pressure curve under constant flow speed of 10 μL/min until 30 minutes for the atheroma (AR) chip (AR 10 ‐AUC 30 ) levels determined by T‐TAS ® , in the assessment of the pharmacological effects of edoxaban, a direct oral anticoagulant, in patients who undergo total knee arthroplasty, and that the AR 10 ‐AUC 30 level was a significant predictor of the efficacy of vitamin K antagonist and other direct oral anticoagulants . We also reported that low AR 10 ‐AUC 30 level was a significant predictor of periprocedural bleeding events in patients with atrial fibrillation who undergo catheter ablation, and that the area under the flow pressure curve under constant flow speed of 10 μL/min until 30 minutes for the platelet (PL) chip (PL 24 ‐AUC 10 ) level measured by T‐TAS ® is a potentially suitable index for the assessment of antiplatelet therapy in CAD patients …”

“…14 We also reported that low AR 10 -AUC 30 level was a significant predictor of periprocedural bleeding events in patients with atrial fibrillation who undergo catheter ablation, 14 and that the area under the flow pressure curve under constant flow speed of 10 lL/min until 30 minutes for the platelet (PL) chip (PL 24 -AUC 10 ) level measured by T-TAS â is a potentially suitable index for the assessment of antiplatelet therapy in CAD patients. 15 The present study was designed to determine the association of periprocedural bleeding events with platelet thrombus formation, which was estimated quantitatively by T-TAS â . Our results highlighted the utility of T-TAS â in predicting periprocedural bleeding in CAD patients undergoing PCI.…”