Description of Response to Aspirin and Clopidogrel in Outpatients With Coronary Artery Disease Using Multiple Electrode Impedance Aggregometry

Gerotziafas, Grigoris T.; Zarifis, John; Bandi, Anastasia; Mossialos, Lambros; Galea, Vasso; Tsinopoulos, George; Chaari, Mourad; Baccouche, Hela; Sassi, Mouna; Elalamy, Ismaı̈l

doi:10.1177/1076029611429122

Cited by 6 publications

(5 citation statements)

References 37 publications

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“…A 10 AU×min corresponds to 1 unit (U). The cut off point for this clopidogrel resistance was 50 U as previously reported [35] . All material used for platelet aggregation study was obtained from the manufacturer.…”

Section: Methodsmentioning

confidence: 89%

Effects of Cytochrome P450 2C19 and Paraoxonase 1 Polymorphisms on Antiplatelet Response to Clopidogrel Therapy in Patients with Coronary Artery Disease

et al. 2014

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Clopidogrel is an antiplatelet prodrug that is recommended to reduce the risk of recurrent thrombosis in coronary artery disease (CAD) patients. Paraoxonase 1 (PON1) is suggested to be a rate-limiting enzyme in the conversion of 2-oxo-clopidogrel to active thiol metabolite with inconsistent results. Here, we sought to determine the associations of CYP2C19 and PON1 gene polymorphisms with clopidogrel response and their role in ADP-induced platelet aggregation. Clopidogrel response and platelet aggregation were determined using Multiplate aggregometer in 211 patients with established CAD who received 75 mg clopidogrel and 75–325 mg aspirin daily for at least 14 days. Polymorphisms in CYP2C19 and PON1 were genotyped and tested for association with clopidogrel resistance. Linkage disequilibrium (LD) and their epistatic interaction effects on ADP-induced platelet aggregation were analysed. The prevalence of clopidogrel resistance in this population was approximately 33.2% (n = 70). The frequencies of CYP2C19*2 and *3 were significantly higher in non-responder than those in responders. After adjusting for established risk factors, CYP2C19*2 and *3 alleles independently increased the risk of clopidogrel resistance with adjusted ORs 2.94 (95%CI, 1.65–5.26; p<0.001) and 11.26 (95%CI, 2.47–51.41; p = 0.002, respectively). Patients with *2 or *3 allele and combined with smoking, diabetes and increased platelet count had markedly increased risk of clopidogrel resistance. No association was observed between PON1 Q192R and clopidogrel resistance (adjusted OR = 1.13, 95%CI, 0.70–1.82; p = 0.622). Significantly higher platelet aggregation values were found in CYP2C19*2 and *3 patients when compared with *1/*1 allele carriers (p = 1.98×10−6). For PON1 Q192R genotypes, aggregation values were similar across all genotype groups (p = 0.359). There was no evidence of gene-gene interaction or LD between CYP2C19 and PON1 polymorphisms on ADP-induced platelet aggregation. Our findings indicated that only CYP2C19*2 and *3 alleles had an influence on clopidogrel resistance. The risk of clopidogrel resistance increased further with smoking, diabetes, and increased platelet count.

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Section: Methodsmentioning

confidence: 89%

Effects of Cytochrome P450 2C19 and Paraoxonase 1 Polymorphisms on Antiplatelet Response to Clopidogrel Therapy in Patients with Coronary Artery Disease

et al. 2014

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“…13 In contrast, the measurement of the response to aspirin and clopidogrel by Multiplate was shown to vary as much as 26%. 41,44 A limitation of this study is that healthy donors were used, and ideally, the study samples should include both healthy controls and samples from those with results that are not within reference range. The samples for the TEG 6s study included samples from subjects on nonsteroidal antiinflammatory drugs, but other types of coagulopathy were not included.…”

Section: Discussionmentioning

confidence: 99%

New-Generation Thromboelastography: Comprehensive Evaluation of Citrated and Heparinized Blood Sample Storage Effect on Clot-Forming Variables

Dias¹,

Haney²,

Mathew³

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Thromboelastography (TEG) is a whole blood, real-time analyzer measuring the viscoelastic properties of the hemostasis process and allowing for individualized goal-directed therapy. However, routine use of TEG requires validation of sample storage effect on clot parameters.Objectives.-To establish the minimum time required for equilibration time and the maximum time for sample storage for all commercially available TEG tests for the new-generation TEG 6s and to determine how those times compare with the older generation TEG 5000.Design.-Citrated and heparinized whole blood samples obtained from 20 healthy donors were analyzed for clot parameters at multiple time points for both the TEG 6s and the TEG 5000. Samples were activated with the citrated multichannel cartridge or the platelet-mapping cartridge in the TEG 6s or with recalcified kaolin in the TEG 5000.Results.-All blood samples yielded TEG parameter results within reference ranges and had a tendency toward hypercoagulable profiles with increased storage time. Sample storage resulted in increased platelet inhibition with significant differences at 4 hours in the plateletmapping cartridge (arachidonic acid percentage of inhibition, P ¼ .002; adenosine diphosphate percentage of inhibition, P ¼ .02).Conclusions.-For nonemergent cases or in a central laboratory setting, all tests provided reliable results for up to 4 hours in the citrated multichannel cartridge and for 3 hours for platelet function information in the plateletmapping cartridge. In emergent/urgent situations in which the sample needs to be run immediately, RapidTEG and functional fibrinogen tests may be preferred.

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“…Typical median ADP-MEA values of patients on dual antiplatelet therapy are 22 U for clopidogrel + ASA (range 0-91) [36], 12 U for prasugrel + ASA (IQR 8-22), and 12 U for ticagrelor + ASA (IQR 7-21) [37]. However, the effect of dual antiplatelet therapy might not be well integrated because ADP-MEA is little influenced by low doses of ASA [38]. The 19 U threshold used in this study and proposed by Mahla et al [12] is the most strongly validated in clinical studies, but only in PCI settings [19].…”

Section: Discussionmentioning

confidence: 99%

Reduction of Preoperative Waiting Time Before Urgent Surgery for Patients on P2Y12 Inhibitors Using Multiple Electrode Aggregometry: A Retrospective Study

Hardy

Dupuis

Dincq

et al. 2020

JCM

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P2Y12 inhibitor discontinuation is essential before most surgical interventions to limit bleeding complications. Based on pharmacodynamic data, fixed discontinuation durations have been recommended. However, as platelet function recovery is highly variable among patients, a more individualized approach based on platelet function testing (PFT) has been proposed. The aim of this retrospective single-centre study was to determine whether PFT using whole blood adenosine diphosphate–multiple electrode aggregometry (ADP–MEA) was associated with a safe reduction of preoperative waiting time. Preoperative ADP–MEA was performed for 29 patients on P2Y12 inhibitors. Among those, 17 patients underwent a coronary artery bypass graft. Twenty one were operated with an ADP–MEA ≥ 19 U (quantification of the area under the aggregation curve), and the waiting time was shorter by 1.6 days (median 1.8 days, IQR 0.5–2.9), by comparison with the current recommendations (five days for clopidogrel and ticagrelor, seven days for prasugrel). Platelet function recovery was indeed highly variable among individuals. With the 19 U threshold, high residual platelet inhibition was associated with perioperative platelet transfusion. These results suggest that preoperative PFT with ADP–MEA could help reduce waiting time before urgent surgery for patients on P2Y12 inhibitors.

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Description of Response to Aspirin and Clopidogrel in Outpatients With Coronary Artery Disease Using Multiple Electrode Impedance Aggregometry

Cited by 6 publications

References 37 publications

Effects of Cytochrome P450 2C19 and Paraoxonase 1 Polymorphisms on Antiplatelet Response to Clopidogrel Therapy in Patients with Coronary Artery Disease

Effects of Cytochrome P450 2C19 and Paraoxonase 1 Polymorphisms on Antiplatelet Response to Clopidogrel Therapy in Patients with Coronary Artery Disease

New-Generation Thromboelastography: Comprehensive Evaluation of Citrated and Heparinized Blood Sample Storage Effect on Clot-Forming Variables

Reduction of Preoperative Waiting Time Before Urgent Surgery for Patients on P2Y12 Inhibitors Using Multiple Electrode Aggregometry: A Retrospective Study

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