TCT-474: Comparison Between Light Transmittance Aggregometry And The Point-of-care Verifynow Assay In The Assessment Of High Post-clopidogrel Platelet Reactivity And Magnitude Of Aggregation Change

2009 ◽  
Vol 104 (6) ◽  
pp. 174D
2018 ◽  
Vol 24 (7) ◽  
pp. 1109-1116 ◽  
Author(s):  
Vincent Roule ◽  
Pierre Ardouin ◽  
Yohan Repessé ◽  
Agnès Le Querrec ◽  
Katrien Blanchart ◽  
...  

Detection of high on-treatment platelet reactivity (HPR) by point-of-care tests has not been validated after successful fibrinolysis for ST-elevation myocardial infarction. We assessed the validity of the point-of-care VerifyNow P2Y12 (VN) and INNOVANCE PFA P2Y (PFA) tests on HPR compared to light transmittance aggregometry (LTA) in these patients. The HPR was identified in 10 (34.5%) patients, 15 (51.7%) patients, and 14 (50%) patients using LTA, VN, and PFA, respectively. Discrepancies were observed between the tests despite significant correlations between platelet reactivity measures by LTA and VN ( r = 0.74; P < .0001) and LTA and PFA ( r = .75; P < .0001). Compared to LTA, VN and PFA were associated with a 92% and 53% and 92% and 64% positive predictive value (PPV) and negative predictive value (NPV), respectively, in detecting HPR. When combined, VN and PFA results yielded 90% and 100% PPV and NPV values if discrepancies between the 2 tests were considered as non-HPR. The VN or PFA identify patients without HPR correctly but overestimate the proportion of HPR patients. The association of the 2 tests, in case of HPR, improves the accuracy of the detection of HPR.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1093-1093
Author(s):  
In-Suk Kim ◽  
Young-Hoon Jeong ◽  
Arum Kim ◽  
Gyeong-Won Lee

Abstract Abstract 1093 Background Flow cytometric analysis of platelet reactivity index of vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) is a suitable test to evaluate the “high post-treatment platelet reactivity (HPPR)”. A reliable cut-off of VASP-P index is needed to identify the HPPR. However, an ideal cut-off identifying HPPR using the VASP-P index remains undetermined. We aimed to show the comparison between light transmittance aggregometry (LTA) and flow cytometric analysis of VASP-P index and assess the cut-offs of identifying HPPR using VASP-P index. Methods We enrolled consecutively patients undergoing percutaneous coronary intervention (PCI) in real clinical practice (n = 516). They all received clopidogrel and aspirin, performed LTA (5 and 20 μmol/l ADP-induced, and 1.6 nmol/l arachidonic acid (AA)-induced PR) and flow cytometric analysis of VASP-P index simultaneously and compared the different platelet measures. Based on previously suggested cut-offs, 5 μmol/l ADP-induced maximal platelet reactivity (PRmax) > 42.9%, 5 μmol/l ADP-induced PRmax > 50%, 20 μmol/l ADP-induced PRmax > 62%, 20 μmol/l ADP-induced PRmax > 64.5%, and 1.6 mmol/l AA-induced PRmax > 20%, the cut-offs of identifying HPPR using flow cytometric analysis of VASP-P were determined by receiver-operating characteristics (ROC) curve analysis. Results Excellent correlations were observed between LTA with ADP-induced PRmax and flow cytometric analysis of VASP-P according to the ROC curve analyses. The ROC curve analyses demonstrated that 5 μmol/l ADP-induced PRmax > 42.9% could distinguish between patients with and without VASP-P index > 54.9% (area under curve [AUC] 0.926, 95% confidence interval (CI) 0.903–0.949, sensitivity 82.8%, and specificity 88.5%, p < 0.001) and 5 μmol/l ADP-induced PRmax > 50% could distinguish between patients with and without VASP-P index > 57.4% (AUC 0.937, 95% CI 0.914–0.961, sensitivity 91.5%, and specificity 85.2%, p < 0.001). ROC curve analysis demonstrated 20 μmol/l ADP-induced PRmax > 62% could distinguish between patients with and without VASP-P index > 55.2% (AUC 0.948, 95% CI 0.927–0.969, sensitivity 95.7%, and specificity 87.3%, p < 0.001) and 20 μmol/l ADP-induced PRmax > 64.5% could distinguish between patients with and without VASP-P index > 55.9% (AUC 0.925, 95% CI 0.900–0.951, sensitivity 88.3%, and specificity 83.0%, p < 0.001), respectively. However, fair correlation was observed between AA-induced PRmax and VASP-P index and 1.6 nmol/l AA-induced PRmax > 20% could distinguish between patients with and without VASP-P index > 52.4% (AUC 0.761, 95% CI 0.719–0.802, sensitivity 68.5%, and specificity 72.7%, p < 0.001). We defined the ideal threshold of VASP-P index > 56%. The VASP-P index > 56% showed a substantial agreement with 5 μmol/l and 20 μmol/l ADP-induced PRmax (Table 1). However, VASP-P index > 56% showed a moderate agreement with 1.6 nmol/l AA)-induced PRmax > 20% (Table 1). Conclusion There are significant correlations between the suggested cut-offs of HPPR. Because VASP-P index > 56 is well matched with 5 μmol/l ADP-induced PRmax > 42.9%, 5 μmol/l ADP-induced PRmax > 50%, 20 μmol/l ADP-induced PRmax > 62%, and 20 μmol/l ADP-induced PRmax > 64.5%., it might suggest that VASP-P index > 56 has a practical implication for stratification of high-risk ischemic events. Disclosures: No relevant conflicts of interest to declare.


Pharmacology ◽  
2017 ◽  
Vol 100 (3-4) ◽  
pp. 127-130 ◽  
Author(s):  
Annemarie Mohring ◽  
Kerstin Piayda ◽  
Lisa Dannenberg ◽  
Saif Zako ◽  
Theresa Schneider ◽  
...  

Platelet inhibition by aspirin is indispensable in the secondary prevention of cardiovascular events. Nevertheless, impaired aspirin antiplatelet effects (high on-treatment platelet reactivity [HTPR]) are frequent. This is associated with an enhanced risk of cardiovascular events. The current gold standard to evaluate platelet hyper-reactivity despite aspirin intake is the light-transmittance aggregometry (LTA). However, pharmacologically, the most specific test is the measurement of arachidonic acid (AA)-induced thromboxane (TX) B2 formation. Currently, the optimal cut-off to define HTPR to aspirin by inhibition of TX formation is not known. Therefore, in this pilot study, we aimed to calculate a TX formation cut-off value to detect HTPR defined by the current gold standard LTA. We measured platelet function in 2,507 samples. AA-induced TX formation by ELISA and AA-induced LTA were used to measure aspirin antiplatelet effects. TX formation correlated nonlinearly with the maximum of aggregation in the AA-induced LTA (Spearman's rho R = 0.7396; 95% CI 0.7208-0.7573, p < 0.0001). Receiver operating characteristic analysis and Youden's J statistics revealed 209.8 ng/mL as the optimal cut-off value to detect HTPR to aspirin with the TX ELISA (area under the curve: 0.92, p < 0.0001, sensitivity of 82.7%, specificity of 90.3%). In summary, TX formation ELISA is reliable in detecting HTPR to aspirin. The calculated cut-off level needs to be tested in trials with clinical end points.


2011 ◽  
Vol 106 (08) ◽  
pp. 331-336 ◽  
Author(s):  
Nicoline J. Breet ◽  
Jochem W. van Werkum ◽  
Heleen J. Bouman ◽  
Johannes C. Kelder ◽  
Christian M. Hackeng ◽  
...  

SummaryBoth heightened platelet reactivity and an occluded infarct related artery (IRA) on initial angiography and at the time of primary percutaneous coronary intervention (PCI) are associated with a worsened clinical outcome in patients with ST-elevation myocardial infarction (STEMI). However, the relationship between platelet reactivity and IRA patency has not yet been established. Consecutive STEMI-patients were enrolled in this study. Patients who had TIMI-flow (thrombolysis in myocardial infarction) 0 or 1 on initial angiography constituted the occluded IRA group and patients having TIMI-flow 2 or 3 comprised the IRA patent group. Platelet function measurements were performed using the PFA-100 COL/ADP cartridge and light transmittance aggregometry without agonist (spontaneous) and after stimulation with adenosine diphosphate (ADP) and arachidonic acid (AA). Ninety-nine patients were enrolled, of whom 49 presented with an occluded IRA. Multivariate analysis identified the following independent factors to be associated with an occluded IRA; short COL/ADP closure time (ORper quartile increase= 0.60; 95% CI, 0.39-.93; p=0.02), the 20 μM ADP-induced light transmittance aggregometry (ORper quartile increase =1.77; 95% CI, 1.15–l2.73; p=0.01) and leukocyte counts (odds ratio [OR]=1.21; 95% CI, 1.05–1.39; p = 0.008). In conclusion, heightened platelet reactivity and elevated leukocyte counts are associated with an occluded IRA upon presentation in STEMI-patients. These results emphasise the importance of potent antithrombotic therapy early after the onset of symptoms, to obtain early recanalisation of the IRA.


2018 ◽  
Vol 46 (5) ◽  
pp. 1866-1875 ◽  
Author(s):  
Masanori Tsujimoto ◽  
Yukiko Enomoto ◽  
Masafumi Miyai ◽  
Yusuke Egashira ◽  
Toru Iwama

Purpose To determine the best platelet function test for in-stent tissue protrusion following carotid artery stenting (CAS). Methods Patients who underwent CAS were recruited prospectively in this observational study. Combination of aspirin 100 mg/day and clopidogrel 75 mg/day was administered for a minimum of 7 days prior to procedure. Platelet aggregation was measured by light transmittance aggregometry (LTA) following stimulation by adenosine diphosphate (ADP), collagen, and thrombin receptor activating peptide (TRAP) and by the point of care assay, VerifyNow which measures aspirin and thienopyridine reaction units. Results In-stent tissue protrusion with maximum projection area of ≥1 mm2 was detected by optical coherence tomography (OCT) in 10/28 (36%) patients. Baseline characteristics were not significantly different between the two in-stent size groups (i.e., ≥1 mm2 vs. <1 mm2) but after stimulation by collagen at 10 and 20 μg/ml, platelet reactivity as measured by LTA was significantly higher in the ≥1 mm2 group compared with the <1 mm2 group. No other differences in platelet function were detected. Conclusions Collagen-induced platelet reactivity was related to in-stent tissue protrusion size following CAS.


2020 ◽  
Vol 9 (18) ◽  
Author(s):  
Fernando Scudiero ◽  
Renato Valenti ◽  
Rossella Marcucci ◽  
Giuseppe D. Sanna ◽  
Anna Maria Gori ◽  
...  

Background Coronary artery disease (CAD) has been recognized as a serious and potentially life‐threatening complication of Hepatitis C Virus (HCV) infection. High on‐treatment platelet reactivity has been associated with high risk of ischemic events in patients with CAD, but data regarding the association with HCV infection are still lacking. This post hoc analysis aims to assess high on‐treatment platelet reactivity, severity of CAD, and long‐term outcomes of patients with acute coronary syndrome (ACS) who were infected with HCV. Methods and Results Patients with ACS who were infected with HCV (n=47) were matched to patients with ACS and without HCV (n=137) for age, sex, diabetes mellitus, hypertension, and renal function. HCV‐infected patients with ACS had higher levels of platelet reactivity (ADP 10 –light transmittance aggregometry, 56±18% versus 44±22% [ P =0.002]; arachidonic acid–light transmittance aggregometry, 25±21% versus 16±15% [ P =0.011]) and higher rates of high on‐treatment platelet reactivity on clopidogrel and aspirin compared with patients without HCV. Moreover, HCV‐infected patients with ACS had higher rates of multivessel disease (53% versus 30%; P =0.004) and 3‐vessel disease (32% versus 7%; P <0.001) compared with patients without HCV. At long‐term follow‐up, estimated rates of major adverse cardiovascular events (cardiac death, nonfatal myocardial infarction, and ischemia‐driven revascularization) were 57% versus 34% ( P =0.005) in HCV‐ and non–HCV‐infected patients with ACS, respectively. In addition, thrombolysis In Myocardial Infarction (TIMI) major bleeding rates were higher in HCV‐infected patients (11% versus 3%; P =0.043) compared with noninfected patients. Multivariable analysis demonstrated that HCV infection was an independent predictor of high on‐treatment platelet reactivity, severity of CAD, and long‐term outcome. Conclusions In this hypothesis‐generating study, patients with ACS and HCV infection showed increased on‐treatment platelet reactivity, more severe CAD, and worse prognosis compared with patients without HCV.


2010 ◽  
Vol 30 (4) ◽  
pp. 486-495 ◽  
Author(s):  
In-Suk Kim ◽  
Young-Hoon Jeong ◽  
Min-Kyung Kang ◽  
Jin-Sin Koh ◽  
Yongwhi Park ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2315-2315
Author(s):  
In-Suk Kim ◽  
Young-Hoon Jeong ◽  
Eun Yup Lee ◽  
Gyeong-Won Lee

Abstract Abstract 2315 Background: Multiple lines of evidence have demonstrated a relationship between high on-treatment platelet reactivity (HPR) measured by multiple platelet assays and adverse clinical ischemic events. Although the Working Group on High On-Treatment Platelet Reactivity recently provided a consensus opinion on the definition of HPR, correlations between HPR cut-offs have not been validated yet. Therefore, we performed this study to provide a comprehensive analysis on the agreement and correlation of HPR cut-offs based on the consensual definition among the different platelet function measurements. Methods: We analyzed data from coronary intervention-treated patients on dual antiplatelet therapy (n = 962). Platelet measures were concurrently 5 and 20 μM ADP-stimulated light transmittance aggregometry (LTA), the VerifyNow P2Y12 analyzer, and flow cytometric analysis of vasodilator-stimulated phosphoprotein (VASP)-platelet reactivity index (PRI). As the Working Group noted, HPR cut-offs were defined as 5 and 20 μM ADP-induced maximal platelet aggregation (PRmax) > 46% and 59%, the VerifyNow P2Y12 assay > 240 P2Y12 reaction unit (PRU), and the VASP-PRI > 50%, respectively. Agreement between the consensual cut-off points of different tests was determined by kappa statistics, and 95% confidence intervals (CI) were also calculated. Receiver-operating characteristics (ROC) curve analysis was performed to identify the matched points for consensual definition-based cut-offs for HPR. Results: The consensual cut-off as 5μmol/l ADP-induced PRmax >46% showed a substantial agreement with 20 μmol/l ADP-induced PRmax, however, this cut-off showed a moderate agreement with the VerifyNow P2Y12 assay > 240 PRU and the VASP-PRI > 50%, respectively (Table 1). Fair correlations were observed between ADP-induced PRmax, the VerifyNow P2Y12 assay, and VASP-PRI according to the ROC curve analyses (Table 2). The cut-offs for 5μmol/l ADP-induced PRmax >46% based HPR matched well with the VerifyNow P2Y12 assay > 284 PRU (AUC 0.791, 95% CI 0.763–0.819, sensitivity 62.0%, and specificity 80.7%, p < 0.001), and the VASP-PRI > 60.3% (AUC 0.788, 95% CI 0.759–0.816, sensitivity 78.2%, and specificity 70.2%, p < 0.001) by the ROC curve analysis, respectively. The consensus-defined cut-offs of VerifyNow P2Y12 assay and VASP index overestimated HPR risk based on LTA cut-offs. Conclusion: Although the VerifyNow P2Y12 and VASP assay correlated significantly with LTA, there are moderate agreements and fair correlations among the consensual cut-offs of HPR. These data suggest the platelet function measurements need to be improved to become clinically used diagnostic tests and the need for a new cut-offs to balance safety and efficacy of P2Y12 receptor antagonists. Further, it still may be too early to define the gold standard method for assessing platelet reactivity and generally acceptable cut-off values. Disclosures: No relevant conflicts of interest to declare.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Daisuke Maruyama ◽  
Toshinori Takagi ◽  
Shigeki Takada ◽  
Hideki kanamaru ◽  
Daizo Ishii ◽  
...  

OBJECTIVE: We evaluated the correlation between point-of-care measurement of on-treatment platelet reactivity and postoperative thromboembolic events in patients undergoing carotid artery stenting (CAS) for atherosclerotic carotid artery stenosis. METHODS: Thirty patients receiving dual antiplatelet treatment, including clopidogrel, before CAS were prospectively enrolled. On-treatment platelet reactivity was measured within 24 h before CAS using both the VerifyNow P2Y12 and aspirin assays and light transmittance aggregometry (LTA) with ADP (LTA-ADP) and collagen (LTA-collagen) as the agonists. The endpoint was defined as the detection of acute ipsilateral ischemia on diffusion-weighted imaging (DWI) within 72 h after CAS. Cut-off values for high on-treatment platelet reactivity were established by receiver operating characteristic curve analysis. RESULTS: A significant correlation was observed between VerifyNow P2Y12 reaction units (PRUs) and LTA-ADP and between VerifyNow aspirin reaction units (ARUs) and LTA-collagen. Small abnormalities were observed on DWI in 9 patients (30.0%), and transient ischemic attack was found in 2 (6.67%). Patients with ischemic events had significantly higher mean pre-CAS PRU values (286.42 ± 85.95 vs. 195.28 ± 90.05; p = 0.027) and lower mean pre-CAS PRU percent inhibition (11.71 ± 12.40 vs. 41.52 ± 22.51; p = 0.0027) than those without ischemic events. In the univariate analysis of the endpoint, 4th quartile PRU values (risk ratio [RR]: 3.0; 95% confidence interval [CI]: 1.00-8.92; p = 0.0533), 1st quartile PRU percent inhibition (RR: 6.33; 95% CI: 1.57-25.42; p = 0.0021), and 4th quartile LTA-ADP (RR: 3.06; 95% CI: 1.17-8.00; p = 0.0341) were found to increase the risk of abnormality detection on postprocedural DWI. The optimal cut-offs for high on-treatment platelet reactivity were 264 for pre-CAS PRU values (area under the curve [AUC]: 0.82; 95% CI: 0.65-0.99), 29 for PRU percent inhibition (AUC: 0.89; 95% CI: 0.77-1.01), and 38 for LTA-ADP (AUC: 0.80, 95% CI: 0.67-0.98). CONCLUSION: This study indicates that the new point-of-care VerifyNow P2Y12 assay might help identify patients who are at higher risk for thromboembolic events after CAS.


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