scholarly journals Differential Impact of Cytochrome 2C19 Allelic Variants on Three Different Platelet Function Tests in Clopidogrel-Treated Patients

2021 ◽  
Vol 10 (17) ◽  
pp. 3992
Author(s):  
Renske H. Olie ◽  
Rachelle R. K. Hensgens ◽  
Petal A. H. M. Wijnen ◽  
Leo F. Veenstra ◽  
Bianca T. A. de Greef ◽  
...  
Keyword(s):  
Platelet Function ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Cyp2c19 Genotype ◽  
Platelet Function Tests ◽  
Related Factors ◽  
Differential Effects ◽  
Function Tests ◽  
Cyp2c19 Polymorphism

On-treatment platelet reactivity in clopidogrel-treated patients can be measured with several platelet function tests (PFTs). However, the agreement between different PFTs is only slight to moderate. Polymorphisms of the CYP2C19 gene have an impact on the metabolization of clopidogrel and, thereby, have an impact on on-treatment platelet reactivity. The aim of the current study is to evaluate the differential effects of the CYP2C19 genotype on three different PFTs. Methods: From a prospective cohort study, we included patients treated with clopidogrel following percutaneous coronary intervention (PCI). One month after PCI, we simultaneously performed three different PFTs; light transmission aggregometry (LTA), VerifyNow P2Y12, and Multiplate. In whole EDTA blood, genotyping of the CYP2C19 polymorphisms was performed. Results: We included 308 patients treated with clopidogrel in combination with aspirin (69.5%) and/or anticoagulants (33.8%) and, based on CYP2C19 genotyping, classified them as either extensive (36.4%), rapid (34.7%), intermediate (26.0%), or poor metabolizers (2.9%). On-treatment platelet reactivity as measured by LTA and VerifyNow is significantly affected by CYP2C19 metabolizer status (p < 0.01); as metabolizer status changes from rapid, via extensive and intermediate, to poor, the mean platelet reactivity increases accordingly (p < 0.01). On the contrary, for Multiplate, no such ordering of metabolizer groups was found (p = 0.10). Conclusions: For VerifyNow and LTA, the on-treatment platelet reactivity in clopidogrel-treated patients correlates well with the underlying CYP2C19 polymorphism. For Multiplate, no major effect of genetic background could be shown, and effects of other (patient-related) variables prevail. Thus, besides differences in test principles and the influence of patient-related factors, the disagreement between PFTs is partly explained by differential effects of the CYP2C19 genotype.

scholarly journals Clopidogrel versus ticagrelor in the treatment of Chinese patients undergoing percutaneous coronary intervention: effects on platelet function assessed by  platelet function tests  and mean platelet volume

2021 ◽  
Author(s):  
Yang Zhang ◽  
Rui Peng ◽  
Xiaojuan Li ◽  
Gaowa Cheng ◽  
Ximing Wang ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Platelet Function ◽  
Mean Platelet Volume ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Chinese Patients ◽  
Platelet Function Tests ◽  
Platelet Volume ◽  
Function Tests ◽  
Percutaneous Coronary

Abstract Background: Knowledge on the pharmacodynamic effects of antiplatelet drugs including clopidogrel and ticagrelor on Asian patients is scarce. We aim to evaluate the effects of the two drugs on platelet reactivity in the treatment of Chinese patients who underwent percutaneous coronary intervention (PCI), using two platelet function tests (PFT). Meanwhile, the relationship between mean platelet volume (MPV), a routine index of platelet size, and high on-treatment platelet reactivity (HPR) is also investigated.Methods: Patients receiving dual antiplatelet therapy (DAPT) were scheduled for the assessment of platelet reactivity at 2–3 days after PCI. Two PFTs, light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP)-FCM assay, were applied in the evaluation of platelet reactivity. The MPV was measured simultaneously with EDTA plasma using a Sysmex XN 2000 automated hematology analyzer.Results: The final study population included the aspirin + clopidogrel group (n = 46) and the aspirin + ticagrelor group (n = 66). In the aspirin + ticagrelor group, the maximal light transmittance (LT) changes in response to 5 µM ADP assessed by LTA was obviously lower than that in the aspirin + clopidogrel group (P < 0.001). The platelet reactivity index (PRI) level in the VASP test was also markedly lower in the group given aspirin and ticagrelor (P < 0.001). There was a significant difference in HPR between the two groups. MPV showed a potent ability to predict the presence of HPR at VASP assay (AUC = 0.788, 95% CI: 0.701–0.875, P < 0.001) in receiver-operating characteristic curve analysis.Conclusions: Compared with clopidogrel, ticagrelor has dramatically greater antiplatelet effect, with a superiority in suppressing platelet function and a lower HPR rate. In addition, there existed a significant independent association between MPV and high prevalence of HPR in the VASP assay.

scholarly journals Clopidogrel versus ticagrelor in the treatment of Chinese patients undergoing percutaneous coronary intervention: effects on platelet function assessed by platelet function tests and mean platelet volume

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang Zhang ◽  
Rui Peng ◽  
Xiaojuan Li ◽  
Gaowa Cheng ◽  
Ximing Wang ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Platelet Function ◽  
Mean Platelet Volume ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Chinese Patients ◽  
Platelet Function Tests ◽  
Platelet Volume ◽  
Function Tests ◽  
Percutaneous Coronary

Abstract Background Knowledge on the pharmacodynamic effects of antiplatelet drugs including clopidogrel and ticagrelor on Asian patients is scarce. We aim to evaluate the effects of the two drugs on platelet reactivity in the treatment of Chinese patients who underwent percutaneous coronary intervention (PCI), using two platelet function tests (PFT). Meanwhile, the relationship between mean platelet volume (MPV), a routine index of platelet size, and high on-treatment platelet reactivity (HPR) is also investigated. Methods Patients receiving dual antiplatelet therapy (DAPT) were scheduled for the assessment of platelet reactivity at 2–3 days after PCI. Two PFTs, light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP)-FCM assay, were applied in the evaluation of platelet reactivity. The MPV was measured simultaneously with EDTA plasma using a Sysmex XN 2000 automated hematology analyzer. Results The final study population included the aspirin + clopidogrel group (n = 46) and the aspirin + ticagrelor group (n = 66). In the aspirin + ticagrelor group, the maximal light transmittance (LT) changes in response to 5 μM ADP assessed by LTA was obviously lower than that in the aspirin + clopidogrel group (P <  0.001). The platelet reactivity index (PRI) level in the VASP test was also markedly lower in the group given aspirin and ticagrelor (P <  0.001). There was a significant difference in HPR between the two groups. MPV showed a potent ability to predict the presence of HPR at VASP assay (AUC = 0.788, 95% CI: 0.701–0.875, P <  0.001) in receiver-operating characteristic curve analysis. Conclusions Compared with clopidogrel, ticagrelor has dramatically greater antiplatelet effect, with a superiority in suppressing platelet function and a lower HPR rate. In addition, there existed a significant independent association between MPV and high prevalence of HPR in the VASP assay.

scholarly journals microRNAs as Promising Biomarkers of Platelet Activity in Antiplatelet Therapy Monitoring

2020 ◽  
Vol 21 (10) ◽  
pp. 3477
Author(s):  
Teresa L. Krammer ◽  
Manuel Mayr ◽  
Matthias Hackl
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Activation ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Therapy Monitoring ◽  
Platelet Inhibition ◽  
High Morbidity ◽  
Platelet Function Tests ◽  
Function Tests ◽  
Plasma Mirna

Given the high morbidity and mortality of cardiovascular diseases (CVDs), novel biomarkers for platelet reactivity are urgently needed. Ischemic events in CVDs are causally linked to platelets, small anucleate cells important for hemostasis. The major side-effect of antiplatelet therapy are life-threatening bleeding events. Current platelet function tests are not sufficient in guiding treatment decisions. Platelets host a broad spectrum of microRNAs (miRNAs) and are a major source of cell-free miRNAs in the blood stream. Platelet-related miRNAs have been suggested as biomarkers of platelet activation and assessment of antiplatelet therapy responsiveness. Platelets release miRNAs upon activation, possibly leading to alterations of plasma miRNA levels in conjunction with CVD or inadequate platelet inhibition. Unlike current platelet function tests, which measure platelet activation ex vivo, signatures of platelet-related miRNAs potentially enable the assessment of in vivo platelet reactivity. Evidence suggests that some miRNAs are responsive to platelet inhibition, making them promising biomarker candidates. In this review, we explain the secretion of miRNAs upon platelet activation and discuss the potential use of platelet-related miRNAs as biomarkers for CVD and antiplatelet therapy monitoring, but also highlight remaining gaps in our knowledge and uncertainties regarding clinical utility. We also elaborate on technical issues and limitations concerning plasma miRNA quantification.

Assessment of platelet function in the laboratory

2009 ◽  
Vol 29 (01) ◽  
pp. 25-31 ◽  
Author(s):  
P. Harrison
Keyword(s):  
Quality Assurance ◽  
Clinical Practice ◽  
Platelet Function ◽  
Light Transmission ◽  
Platelet Function Tests ◽  
Platelet Function Testing ◽  
Clinical Laboratories ◽  
Function Tests ◽  
Whole Blood Aggregometry ◽  
Function Testing

SummaryPlatelet function testing is essential for the diagnosis of congenital/acquired bleeding disorders and may be useful for the prediction of surgical bleeding. Nowadays there is also much interest in monitoring the efficacy of anti-platelet therapy and measuring platelet hyper-function. However, this often presents clinical laboratories with significant challenges as platelet function tests are complex, poorly standardized, time consuming and quality assurance is not straightforward. There are also few comprehensive modern guidelines available and many recent published surveys have revealed poor standardization between laboratories.Up until the late 1980’s the traditional clinical platelet function tests that were available were the bleeding time (BT), light transmission (LTA) and whole blood aggregometry (WBA) and various biochemical assays. These were also usually performed within specialized research and clinical laboratories. Since the last BCSH guidelines were published in 1988 a variety of new platelet function tests have become available. These include flow cytometry and an ever increasing choice of new commercial instruments. Although the potential clinical utility of the new assays is emerging some have not yet entered into routine clinical practice. It is encouraging that a number of standardization committees (e. g. CLSI, BCSH and ISTH Platelet Physiology SSC) are now beginning to produce new platelet function testing guidelines and this will hopefully improve clinical practice, quality assurance and result in less variability between different laboratories.

Comparison of current platelet functional tests for the assessment of aspirin and clopidogrel response

2016 ◽  
Vol 116 (10) ◽  
pp. 638-650 ◽  
Author(s):  
Jean-Claude Bordet ◽  
Claude Negrier ◽  
Yesim Dargaud ◽  
Sandra Le Quellec
Keyword(s):  
Platelet Function ◽  
Light Transmission ◽  
Platelet Response ◽  
Platelet Function Tests ◽  
Clopidogrel Resistance ◽  
Function Tests ◽  
Function Analyzer ◽  
Clopidogrel Therapy ◽  
Whole Blood Aggregometry ◽  
Platelet Function Analyzer

SummaryThe two most widely used antiplatelet drugs in the world are aspirin and clopidogrel. However, some patients on aspirin and/or clopidogrel therapy do not respond appropriately to either aspirin or clopidogrel. This phenomenon is usually called “aspirin/clopidogrel resistance”. Several platelet function tests have been used in various studies for the assessment of aspirin and clopidogrel resistance in healthy individuals and patients admitted in cardiology departments. An accurate assessment of platelet response to aspirin/clopidogrel could benefit patients by proposing tailored-antiplatelet therapy based on test results. However, there is a clear lack of standardisation of such techniques and their analytical variability may induce misinterpretation. After a quick report of the mechanisms responsible for aspirin/clopidogrel resistance, we describe the pre-analytical aspects and the analytical performances of current platelet function tests (Light-transmission aggregometry, whole-blood aggregometry, VerifyNow®, Platelet Function Analyzer®, thromboelastography, VASP assay) that are used for the assessment of aspirin/clopidogrel resistance in clinical studies. Considering the different variables that have to be taken into account with each of the platelet function tests, a particular attention should be paid when interpreting results.

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