A novel approach of platelet function test for prediction of attenuated response to clopidogrel

Ezer, Erzsébet; Schrick, Diana; Tökés-Füzesi, Margit; Szekeres, L.; Bogár, Lajos; Molnár, Tihamér

doi:10.3233/ch-190580

Cited by 13 publications

(15 citation statements)

References 16 publications

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“…The study protocoll was approved by the University of Pecs Clinical Centre Regional and Institutional Research Ethics Comittee (8). Written informed consent was obtained from each patient.…”

Section: Subjectsmentioning

confidence: 99%

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Novel Predictors of Future Vascular Events in Post-stroke Patients—A Pilot Study

et al. 2021

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Introduction: A modified platelet function test (mPFT) was recently found to be superior compared to impedance aggregometry for selection of post-stroke patients with high on-treatment platelet reactivity (HTPR). We aimed to explore some peripheral blood cell characteristics as predictors of recurrent ischemic episodes. The predictive value of mPFT was also assessed in a cohort followed up to 36 months regarding recurrent ischemic vascular events.Methods: As a novelty, not only whole blood (WB), but after 1-h gravity sedimentation the separated upper (UB) and lower half blood (LB) samples were analyzed including neutrophil antisedimentation rate (NAR) in 52 post-stroke patients taking clopidogrel. Area under the curve (AUC, AUCupper and AUClower, respectively) was separately measured by Multiplate in the WB, UB and LB samples to characterize ex vivo platelet aggregation in the presence of ADP. Next, the occurrence of vascular events (stroke, acute coronary syndrome, ACS) were evaluated during 36-month follow-up.Results: A total of 11 vascular events (stroke n = 5, ACS n = 6) occurred during the follow-up period. The AUCupper was significantly higher in patients with recurrent stroke compared to those with uneventful follow-up (p = 0.03). The AUCupper with a cut-off value ≥70 based on the mPFT, was able to predict all stroke events (p = 0.01), while the total vascular events were independently predicted by NAR with a sensitivity of 82% and specificity of 88%.Conclusions: A combination of NAR reflecting the inflammatory state and AUCupper indicating HTPR may provide a better prediction of recurrent ischemic events suggesting a better selection of patients at risk, thus providing an individually tailored vascular therapy.

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Section: Subjectsmentioning

confidence: 99%

“…However, the prevalence of HTPR was shown to vary depending on the definition and assay used (7). A modified platelet function test (mPFT) was recently found to be superior compared to conventional Multiplate Electrode Aggregometry for selection of post-stroke patients with HTPR (8).…”

Section: Introductionmentioning

confidence: 99%

Novel Predictors of Future Vascular Events in Post-stroke Patients—A Pilot Study

et al. 2021

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“…Platelet function guided antiplatelet therapy is getting more important because of increased resistance from antiplatelet drugs like aspirin and clopidogrel which is included in most AIS patients, and they experience different adverse vascular events due to the treatment failure. It also helps in the tailored or personalized antiplatelet therapy in the patients who have high on-treatment platelet reactivity and in the early detection of adverse vascular events ( 7 , 8 ). So, it is important to measure the inhibition of the platelet function in patients with AIS who have HTPR ( 72 ).…”

Section: Antiplatelet Resistancementioning

confidence: 99%

“…So, it is important to measure the inhibition of the platelet function in patients with AIS who have HTPR ( 72 ). The different platelet function testing methods are bleeding time, light transmission platelet aggregation (LTA), impedance platelet aggregation, lumi-aggregometry, and tests based on platelet function methods combined with viscoelastic tests, such as Thromboelastographs (TEGs)/platelet mapping systems, Rotational Thromboelastometry (ROTEM) platelets, and others, where Flow Cytometry is used to test the platelet activation, and Radio- or Enzyme-Linked Immuno Assay measure the thromboxane A2 metabolites ( 8 , 57 , 73 – 75 ).…”

Section: Antiplatelet Resistancementioning

confidence: 99%

Biomarkers for Antiplatelet Therapies in Acute Ischemic Stroke: A Clinical Review

et al. 2021

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Stroke is one of the world's leading causes of disability and death. Antiplatelet agents are administered to acute ischemic stroke patients as secondary prevention. Clopidogrel involves biotransformation by cytochrome P450 (CYP) enzymes into an active metabolite, and single nucleotide polymorphisms (SNPs) can influence the efficacy of this biotransformation. Despite the therapeutic advantages of aspirin, there is significant inter-individual heterogeneity in response to this antiplatelet drug. In this clinical review, the recent advances in the biomarkers of antiplatelet agents in acute ischemic stroke are discussed. The studies reviewed herein highlight the clinical relevance of antiplatelet resistance, pharmacotherapy of antiplatelet agents predicting drug response, strategies for identifying aspirin resistance, pharmacogenetic variants of antiplatelet agents, miRNAs, and extracellular vesicles (EVs) as biomarkers toward the personalized approach in the management of acute ischemic stroke. The precise pathways contributing to antiplatelet resistance are not very well known but are presumably multi-factorial. It is essential to understand the clinical relevance of clopidogrel and aspirin-related single nucleotide polymorphism (SNPs) as potential predictive and prognostic biomarkers. Prasugrel is a next-generation antiplatelet agent that prevents ADP-platelet activation by binding irreversibly to P2Y12 receptor. There are sporadic reports of prasugrel resistance and polymorphisms in the Platelet endothelial aggregation receptor-1 (PEAR1) that may contribute to a change in the pharmacodynamics response. Ticagrelor, a direct-acting P2Y12-receptor antagonist, is easily absorbed and partly metabolized to major AR-C124910XX metabolite (ARC). Ticagrelor's primary active metabolite, ARC124910XX (ARC), is formed via the most abundant hepatic cytochrome P450 (CYP) enzyme, CYP3A4, and CYP3A5. The integration of specific biomarkers, genotype as well as phenotype-related data in antiplatelet therapy stratification in patients with acute ischemic stroke will be of great clinical significance and could be used as a guiding tool for more effective, personalized therapy.

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“…In our own cohort, we combined the examination of endothelial and platelet-derived microvesicles and ex vivo platelet function in post-stroke patients taking clopidogrel. Both measurements were performed in whole blood and from the lower and upper blood fractions separated after 1-hour gravity sedimentation by the analogy with erythrocyte sedimentation rate (ESR) (29). We observed that the total MV number measured in the lower fraction after sedimentation showed a negative correlation with the area under the curve (AUC, reflecting the aggregation) value measured by Multiplate (Roche, Switzerland).…”

Section: Screening For High-on-treatment Platelet Reactivitymentioning

confidence: 99%

Prevention of Non-Cardiogenic Ischemic Stroke: Towards Personalized Stroke Care

Molnár

Csécsei

2021

Stroke

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Despite diagnostic advances and new evidence on how to best treat patients with ischemic stroke, the risk of stroke recurrence remains unacceptably high. Therefore, there is a great need for novel therapies and markers to guide risk stratification, reveal stroke aetiology, identify patients who may benefit most from interventions, predict risk for another stroke, and recognize the risk of short-term complications or unfavorable long-term outcomes. The purpose of this chapter is to provide an update on: (i) emerging markers in atherothrombotic stroke; (ii) role of systemic inflammation in contributing to stroke occurrence; (iii) the main antiplatelet agents that have been successfully used in the secondary prevention of non-cardiogenic ischemic stroke and transient ischemic attack; (iv) screening for high-on-treatment platelet reactivity after stroke; and (v) to explore novel and effective antiplatelet strategies for the secondary prevention of ischemic stroke. Rising questions such as indications for antiplatelet therapy after a successful recanalisation following acute ischemic stroke should be answered in the future to

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A novel approach of platelet function test for prediction of attenuated response to clopidogrel

Cited by 13 publications

References 16 publications

Novel Predictors of Future Vascular Events in Post-stroke Patients—A Pilot Study

Novel Predictors of Future Vascular Events in Post-stroke Patients—A Pilot Study

Biomarkers for Antiplatelet Therapies in Acute Ischemic Stroke: A Clinical Review

Prevention of Non-Cardiogenic Ischemic Stroke: Towards Personalized Stroke Care

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