Thromboxane Formation Assay to Identify High On-Treatment Platelet Reactivity to Aspirin

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.

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Malondialdehyde Assay in the Evaluation of Aspirin Antiplatelet Effects

Pharmacology ◽

10.1159/000493754 ◽

2018 ◽

Vol 103 (1-2) ◽

pp. 23-29 ◽

Cited By ~ 1

Author(s):

Amin Polzin ◽

Lisa Dannenberg ◽

Theresa Schneider ◽

Betül Knoop ◽

David Naguib ◽

...

Keyword(s):

Cardiovascular Events ◽

Operating Characteristic ◽

Light Transmission ◽

Platelet Reactivity ◽

Area Under The Curve ◽

Healthy Individuals ◽

Antibody Assay ◽

Light Transmission Aggregometry ◽

Artery Disease

Aspirin is essential in secondary prevention of patients after myocardial infarction and with coronary artery disease. However, impaired pharmacodynamic response to aspirin is frequent (high on-treatment platelet reactivity [HTPR]). This leads to an enhanced prevalence of cardiovascular events and to an impaired clinical outcome. The current specific assays to evaluate aspirin antiplatelet effects are complex, time-consuming and demand for a high laboratory expertise. Therefore, we developed a potentially bedside assay based on the determination of malondialdehyde (MDA). MDA is a by-product of the thromboxane (TX) formation, which is synthesized in equimolar concentrations. In this study, we compared this MDA assay to the conventional assays in determination of pharmacodynamic aspirin response. For this, aspirin antiplatelet effects were measured in 22 healthy individuals and 63 aspirin treated patients using TX B2 formation enzyme-linked antibody assay, arachidonic acid induced light transmission aggregometry (LTA) and the new fluorometric MDA assay. In patients, MDA levels correlated well with TX formation (R = 0.81; 95% CI 0.69–0.88; p < 0.001) and LTA (R = 0.84; CI 0.74–0.91; p < 0.001). Receiver operating characteristic analyses revealed that the MDA assay does detect HTPR to aspirin sufficiently (area under the curve: 0.965; p < 0.001). The optimal cut-off was > 128 nmol/L (sensitivity of 100%, specificity of 91%). The new MDA assay is reliable in detecting HTPR. It is highly specific in the evaluation of antiplatelet effects by aspirin. This promising and potential bedside assay needs to be evaluated in clinical practice.

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4423 Impact of Gender on High On-Treatment Platelet Reactivity (HPR) and Major Adverse Cardiovascular Events (MACEs) in Caribbean Hispanic patients using Clopidogrel

Journal of Clinical and Translational Science ◽

10.1017/cts.2020.336 ◽

2020 ◽

Vol 4 (s1) ◽

pp. 109-110

Author(s):

Hector Jose Nunez Medina ◽

Jorge Duconge ◽

Luis A. Velez ◽

Laura I. Fernandez ◽

Orlando Arce

Keyword(s):

Logistic Regression ◽

Puerto Rico ◽

Cardiovascular Events ◽

Platelet Reactivity ◽

Arterial Disease ◽

Platelet Inhibition ◽

Major Adverse Cardiovascular Events ◽

And Gender ◽

One Year ◽

Peripheral Arterial

OBJECTIVES/GOALS: The use of P2Y12 receptor inhibitors like Clopidogrel is crucial in the prevention of thrombotic events in patients with coronary artery disease, peripheral arterial disease, and cerebrovascular disease. Variation in the level of platelet inhibition is present in many patients, and it is associated with the occurrence of major adverse cardiovascular events (MACEs). The term High-on treatment platelet reactivity (HTRP) is used to describe impaired antiplatelet inhibition while on Clopidogrel. Multiple factors have been associated with the presence of HTPR in patients with CAD and PAD, including CYP2C19 loss of function polymorphism, drug-drug interactions, and medical comorbidities. Gender differences are another factor that might influence the levels of platelet inhibition while on Clopidogrel and hence, HTPR. Differences by Gender exist in platelet biology, count, and activation. The evidence for the influence of Gender in HTPR is limited, but a possible association has been described. In this study, we described the association of Gender with HTPR and Major Adverse Cardiovascular Events (MACEs) occurrence. The data is from a sample of Hispano-Caribbean patients on Clopidogrel therapy alone or in combination with Aspirin that were retrospectively evaluated from an ongoing trial in Puerto Rico. The result of this study provided evidence of the influence that Gender has on antiplatelet therapy function and MACEs occurrence. METHODS/STUDY POPULATION: The population in the study consisted of Hispano-Caribbean patients using Clopidogrel alone or in combination with Aspirin for coronary artery disease, peripheral arterial disease, or cerebrovascular disease. The sample was obtained from multiple hospital institutions with cardiovascular services in Puerto Rico during the years 2016-2019. Patients were part of the ongoing trial, “Adopting a precision medicine paradigm in Puerto Rico: leveraging ancestral diversity to identify predictors of Clopidogrel response in Caribbean Hispanics.” The sample size consisted of 150 patients. Participants were recruited during routine medical care, pre-admission evaluation for elective cardiac procedures, or during hospitalization in the participating institutions. Platelet reactivity testing was performed with the system Verify Now® to determine PRU values, and High on-treatment platelet reactivity was defined as PRU ≥208. One year after recruitment, the patients were re-evaluated for the occurrence of MACEs. The association of the variables HTPR, occurrence of MACEs, and Gender were assessed using logistic regression in addition to the role of HTPR and Gender for predicting MACE occurrence. The analysis was done using the statistic software Intellectus ©. RESULTS/ANTICIPATED RESULTS: The sample consisted of 67 females and 83 males with and Mean age of 67.87 years and 61.11 years, respectively. The prevalence of HTPR in the sample was 32.67 % (n = 49) with 36% (n = 24) for females, and 30%(n = 25) for males. The mean PRU values were 179.54 for females and 170.81 for males. The percentage of MACEs one year after recruitment was 29.33 % (n = 44) with 43% on females (n = 19), and 57% on males (n = 25). Logistic regression for Gender predicting HTPR was non-significant with a χ2(2) = 0.55, p = .758, and McFadden R2 = 0.00. Also, logistic regression for the effects of Gender and HTPR on the Odds of MACEs occurrence was not significant based on a model with an alpha of 0.05, χ2(2) = 1.99, p = .370, and McFadden R2 = 0.01. DISCUSSION/SIGNIFICANCE OF IMPACT: The sample consisted of 67 females and 83 males with and Mean age of 67.87 years and 61.11 years, respectively. The prevalence of HTPR in the sample was 32.67 % (n = 49) with 36% (n = 24) for females, and 30%(n = 25) for males. The mean PRU values were 179.54 (±70.42) for females and 170.81(±64.89) for males. The percentage of MACEs one year after recruitment was 29.33 % (n = 44) with 43% on females (n = 19), and 57% on males (n = 25). Logistic regression for Gender predicting HTPR was non-significant with a χ2(2) = 0.55, p = .758, and McFadden R2 = 0.00. Also, logistic regression for the effects of Gender and HTPR on the odds of MACEs occurrence was not significant based on a model with an alpha of 0.05, χ2(2) = 1.99, p = .370, and McFadden R2 = 0.01.

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H2FPEF Score as a Prognostic Value in HFpEF Patients

American Journal of Hypertension ◽

10.1093/ajh/hpz108 ◽

2019 ◽

Vol 32 (11) ◽

pp. 1082-1090 ◽

Cited By ~ 7

Author(s):

Daisuke Sueta ◽

Eiichiro Yamamoto ◽

Taiki Nishihara ◽

Takanori Tokitsu ◽

Koichiro Fujisue ◽

...

Keyword(s):

Cardiovascular Events ◽

Area Under The Curve ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Rank Test ◽

Characteristic Analysis ◽

Simple Method ◽

Ventricular Ejection Fraction ◽

Log Rank Test ◽

Cerebrovascular Events

Abstract Background The H2FPEF score is recognized as a simple method to diagnose heart failure (HF) with preserved left ventricular ejection fraction (HFpEF). We investigated the value of the H2FPEF score in predicting subsequent cardiovascular events in HFpEF patients. Methods This study was a retrospective, single-center, observational study. We calculated the H2FPEF scores for 404 consecutive HFpEF patients. Subjects were subdivided into low- (0–3), intermediate- (4–6), and high-score (7–9) groups and followed for 50 months. The primary and secondary endpoints were composite cardiovascular/cerebrovascular events (cardiovascular death, nonfatal myocardial infarction, unstable angina pectoris, hospitalization for HF decompensation, and nonfatal stroke) occurrence and HF-related events (hospitalization for HF decompensation) occurrence at 50 months, respectively. Results Kaplan–Meier analyses demonstrated a significantly higher incidence of cardiovascular/cerebrovascular events among those with a higher H2FPEF score (log-rank test, P = 0.005). The HF-related event rate was higher in proportion to the H2FPEF score (log-rank test, P < 0.001). Multivariate Cox hazard analyses identified the H2FPEF score (per 1 point) as an independent predictor of cardiovascular and HF-related events (hazard ratio [HR], 1.179; 95% confidence interval [CI], 1.066–1.305; P = 0.001 and HR, 1.288; 95% CI, 1.134–1.463; P = 0.001, respectively). Receiver operating characteristic analysis showed that the H2FPEF significantly predicted cardiovascular events (area under the curve [AUC], 0.626; 95% CI, 0.557–0.693; P < 0.001) and HF-related events (AUC, 0.680; 95% CI, 0.600–0.759; P < 0.001). The cutoff H2FPEF score was 5.5 for the identification of cardiovascular and HF-related events. Conclusion The H2FPEF score might be a potentially useful marker for the prediction of cardiovascular and HF-related events in HFpEF patients. Clinical Trails Registration Trail Number UMIN000029600.

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Cardiovascular events occur independently of high on-aspirin platelet reactivity and residual COX-1 activity in stable cardiovascular patients

Thrombosis and Haemostasis ◽

10.1160/th15-11-0864 ◽

2016 ◽

Vol 116 (08) ◽

pp. 356-368 ◽

Cited By ~ 10

Author(s):

Kazuyuki Nagatsuka ◽

Shigeki Miyata ◽

Akiko Kada ◽

Atsushi Kawamura ◽

Jyoji Nakagawara ◽

...

Keyword(s):

Cardiovascular Events ◽

Cox Regression ◽

Platelet Reactivity ◽

Thrombus Formation ◽

Cardiovascular Death ◽

Characteristic Analysis ◽

Cardiovascular Patients ◽

Definition Of ◽

Induced Aggregation ◽

Cox 1

SummarySeveral studies have indicated that approximately 25% of patients treated with aspirin exhibit high on-treatment platelet reactivity (HTPR), which is potentially associated with cardiovascular events (CVEs). However, this association is still controversial, since the mechanisms by which HTPR contributes to CVEs remain unclear and a no standardised definition of HTPR has been established. To determine whether HTPR is associated with CVE recurrence and what type of assay would best predict CVE recurrence, we conducted a multicentre prospective cohort study of 592 stable cardiovascular outpatients treated with aspirin monotherapy for secondary prevention. Their HTPR was determined by arachidonic acid- or collagen-induced aggregation assays using two different agonist concentrations. Residual cyclooxygenase (COX)-1 activity was assessed by measuring serum thromboxane (TX)B2 or urinary 11-dehydro TXB2. Shear-induced platelet thrombus formation was also examined. We followed all patients for two years to evaluate how these seven indexes were related to the recurrence of CVEs (cerebral infarction, transient ischaemic attack, myocardial infarction, unstable angina, revascularisation, other arterial thrombosis, or cardiovascular death). Of 583 patients eligible for the analysis, CVEs occurred in 69 (11.8%). A Cox regression model identified several classical risk factors associated with CVEs. However, neither HTPR nor high residual COX-1 activity was significantly associated with CVEs, even by applying cut-off values suggested in previous reports or a receiver-operating characteristic analysis. In conclusion, recurrence of CVEs occurred independently of HTPR and residual COX-1 activity. Thus, our findings do not support the use of platelet or COX-1 functional testing for predicting clinical outcomes in stable cardiovascular patients.Supplementary Material to this article is available at www.thrombosis-online.com.

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Baseline Platelet Reactivity as Determined by TRAP-6 Induced Aggregation in Whole Blood Is Related to the Rate of Non-Responsiveness to Clopidogrel

Blood ◽

10.1182/blood.v112.11.5362.5362 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5362-5362 ◽

Cited By ~ 3

Author(s):

Michael Spannagl ◽

Csilla Jambor

Keyword(s):

Arachidonic Acid ◽

Whole Blood ◽

Platelet Reactivity ◽

Area Under The Curve ◽

Dual Therapy ◽

Platelet Inhibition ◽

Multiple Electrode Aggregometry ◽

A Minor ◽

Induced Aggregation ◽

Multiple Electrode

Abstract Background: Platelet inhibition by clopidogrel is often determined using ADP induced aggregometry. TRAP-6 stimulates platelets via the PAR receptors and is influenced to a much lesser extend by aspirin or clopidogrel. The value of the determination of TRAP-6 induced aggregometry in patients treated with clopidogrel is unknown. We evaluated the relation of clopidogrel non-responsiveness as determined by multiple electrode aggregometry (MEA) (1) vs. TRAP-6 induced aggregation. MEA provides a measurement of platelet aggregation in whole blood by monitoring changes in electrical impedance via disposable test cells each containing two pairs of electrodes (1). Methods: Following IRB approval hirudin-anticoagulated blood (Dynabyte, Munich, Germany) was sampled from 993 patients. Aggregation induced by arachidonic acid (0.5 mM), ADP (6.4 μM) or TRAP-6 (32μM) was determined in whole blood using a new generation impedance aggregometer. The device is called Multiplate analyzer (Dynabyte, Munich, Germany), indicating the multiplicity of channels and sensors per channel of the device. After dilution (1:2 with 0.9% NaCl solution) of hirudin-anticoagulated whole blood and stirring for three minutes in the test cuvettes at 37°C, the activator was added and aggregation was continuously recorded for six minutes. The increase of impedance due to the attachment of platelets to the electrodes is detected for each sensor unit separately and transformed to arbitrary aggregation units. The aggregation is quantified as area under the curve (AUC). Results: 618 patients were on chronic therapy with 100 mg aspirin/d, 295 patients on clopidogrel 75 mg/d (237 on dual therapy). Aspirin therapy had no influence on TRAP-6- induced aggregation (112+−260 vs. 110+−25; mean +− sd; aspirin vs. no aspirin, p> 0.05 Mann-Whitney U-test). In contrast clopidogrel induced a minor but significant reduction of TRAP6-induced aggregation (107+− 277 vs. 113+−246; p<0.05). Patients on clopidogrel had a significantly lower ADP induced aggregation (41+−30 vs. 86 +−33) compared to controls (p<0.05), and patients on aspirin had a significantly lower arachidonic acid induced aggregation compared to controls (23+−28 vs. 94 +− 35, p<0.05). 89 of 295 patients (30%) were stratified as clopidogrel non-responders based on the cut-off presented in (2). Patients were divided into 4 quartiles (q1-4) depending on their TRAP-6 induced aggregation. The rate of non-responsiveness in Q1 was 8.1%, in Q2 20%, in Q3 38% and 54% in Q4. ADPinduced aggregation was significantly higher in Q4 than in any other quartile (p<0.05). Conclusion: A high TRAP-6 induced aggregation is associated with an increased rate of clopidogrel non-responsiveness as determined by multiple electrode aggregometry. TRAP-6 induced aggregometry seems to indicate the global platelet potential and might allow a prediction of clopidogrel responsiveness before the induction of therapy.

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The Assessment of High Post-Clopidogrel Platelet Reactivity Using the Vasodilator-Stimulated Phosphoprotein Phosphorylation Index – Comparison with Light Transmittance Aggregometry.

Blood ◽

10.1182/blood.v116.21.1093.1093 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1093-1093

Author(s):

In-Suk Kim ◽

Young-Hoon Jeong ◽

Arum Kim ◽

Gyeong-Won Lee

Keyword(s):

Roc Curve ◽

Platelet Reactivity ◽

Flow Cytometric Analysis ◽

Curve Analysis ◽

Light Transmittance ◽

Reactivity Index ◽

Roc Curve Analysis ◽

Flow Cytometric ◽

Light Transmittance Aggregometry ◽

P Index

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.

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Clopidogrel Resistance in Lower Extremity Arterial Endovascular Interventions

Current Pharmaceutical Design ◽

10.2174/1381612825666190101111123 ◽

2019 ◽

Vol 24 (38) ◽

pp. 4554-4557

Author(s):

Kyle M. Markel ◽

Efthymios D. Avgerinos

Keyword(s):

Lower Extremity ◽

Platelet Reactivity ◽

Large Population ◽

Platelet Inhibition ◽

Light Transmittance ◽

Loss Of Function ◽

Clopidogrel Resistance ◽

Endovascular Interventions ◽

Prospective Trials ◽

One Year

Antiplatelet pharmacotherapy for endovascular interventions has been widely adopted, with clopidogrel being one of the most common agents prescribed. A fraction of patients is resistant to clopidogrel resulting in decreased platelet inhibition despite adequate use. This finding is often termed high on-treatment platelet reactivity (HPR) and may lead to decreased patency in lower extremity arterial endovascular interventions. Current literature on HPR with lower extremity arterial endovascular interventions is limited to only a few studies. Resistance to clopidogrel is largely a result of CYP2C19 enzyme loss of function alleles. Several tests are available to measure clopidogrel resistance but light transmittance aggregometry remains the gold standard, yet direct genetic testing may be more reliable. One-year patency rates following lower extremity arterial endovascular interventions in patients with clopidogrel resistance (HPR) range between 35%-83% whereas those with the proper response to clopidogrel range between 73%-100%. Patients with decreased CYP2C19 activity show a significant decrease in one-year patency of endovascular femoropopliteal interventions (35% vs. 73%; p=0.006). Among patients tested for platelet function after in-stent thrombosis, up to 53% are resistant to clopidogrel. Lack of robust data limits our ability to predict patency in lower extremity arterial interventions for patients with HPR, but there is little doubt that longer patency seems to favor non-HPR patients. Large population, prospective trials are needed to guide our practice.

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Rationale and Design of ST-ON-SET: Assessment of Antiplatelet Effect after Ticagrelor Loading Dose in STEMI pPatients and NSTEMI Patients

International Cardiovascular Forum Journal ◽

10.17987/icfj.v8i0.320 ◽

2016 ◽

Vol 8 ◽

Author(s):

Hongyi Wu ◽

Yinman Wang ◽

Huajie Xu ◽

Juying Qian ◽

Junbo Ge

Keyword(s):

Preliminary Investigation ◽

Plasma Concentrations ◽

Unmet Need ◽

Underlying Mechanism ◽

Platelet Inhibition ◽

Light Transmittance ◽

Chinese Patients ◽

Loading Dose ◽

Open Label ◽

Light Transmittance Aggregometry

Background: Delayed platelet inhibition by ticagrelor has been initially documented in STEMI subjects. To the best of our knowledge, no data exists about the direct description of early onset of platelet inhibition after ticagrelor loading dose (LD) in different clinical forms of ACS, especially in Chinese patients. The ST-ON-SET study is designed to address this unmet need. Method/Design: The ST-ON-SET study is a single center, prospective, observational, open-label, investigator-initiated study. Platelet inhibition assessed by Light transmittance aggregometry (LTA) and plasma concentrations of ticagrelor and its metabolites would be investigated serially. The primary outcome is the inhibition of platelet aggregation measured by LTA at 2 hours after ticagrelor LD. Moreover, baseline inflammatory and thrombotic biomarkers would be measured to investigate the potential underlying influences of platelet inhibition.Conclusion: The study is designed to characterize pharmacokinetic and pharmacodynatic profiles of ticagrelor LD in Chinese STEMI and NSTEMI patients. Furthermore, preliminary investigation of the underlying mechanism of initial delayed platelet inhibition by ticagrelor would be conducted.

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The relationship between platelet reactivity and infarct-related artery patency in patients presenting with a ST-elevation myocardial infarction

Thrombosis and Haemostasis ◽

10.1160/th10-08-0528 ◽

2011 ◽

Vol 106 (08) ◽

pp. 331-336 ◽

Cited By ~ 7

Author(s):

Nicoline J. Breet ◽

Jochem W. van Werkum ◽

Heleen J. Bouman ◽

Johannes C. Kelder ◽

Christian M. Hackeng ◽

...

Keyword(s):

Myocardial Infarction ◽

Platelet Reactivity ◽

St Elevation Myocardial Infarction ◽

Light Transmittance ◽

Timi Flow ◽

Light Transmittance Aggregometry ◽

Infarct Related Artery ◽

Leukocyte Counts ◽

St Elevation ◽

The Relationship

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.

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Comparison of acetylsalicylic acid and clopidogrel non-responsiveness assessed by light transmittance aggregometry and PFA-100® in patients undergoing neuroendovascular procedures

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-0737 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Christina C. Rolling ◽

Julia Tomada ◽

Andreas M. Frölich ◽

Brigitte Holst ◽

Katharina Holstein ◽

...

Keyword(s):

Acetylsalicylic Acid ◽

Adenosine Diphosphate ◽

Platelet Inhibition ◽

Adverse Outcomes ◽

Light Transmittance ◽

Prostaglandin E ◽

Activity Levels ◽

Platelet Disaggregation ◽

Light Transmittance Aggregometry ◽

Function Analyzer

AbstractObjectivesDual platelet inhibition is commonly used for prevention of cardiovascular events in patients undergoing neuroendovascular procedures. Non-responsiveness to platelet inhibitors may be associated with adverse outcomes. The aim of this study was to evaluate the reliability of the platelet function analyzer PFA-100® in comparison to light transmittance aggregometry (LTA) for monitoring clopidogrel and acetylsalicylic acid (ASA) non-responsiveness in a cohort of patients treated for intracranial aneurysm or cranial artery stenosis.MethodsNon-responsiveness to clopidogrel and ASA was assessed by LTA using adenosine diphosphate (ADP) and arachidonic acid and by PFA-100® with the ADP/prostaglandin E1 (PGE1) and collagen/epinephrine cartridges, respectively.ResultsA total of 203 patients (145 females; median age, 57 years) were analyzed. Agreement between the two tests was poor for clopidogrel non-responsiveness (ƙ=0.19) and not better than chance for ASA non-responsiveness (ƙ=0.01). Clopidogrel non-responsiveness by LTA and PFA-100® was associated with higher von Willebrand factor antigen and activity levels. ADP-induced platelet disaggregation was lower in patients with clopidogrel non-responsiveness as assessed by PFA-100®. Clopidogrel non-responsiveness by LTA was associated with a higher prevalence of diabetes and a higher body mass index (BMI). Adverse outcomes (death, thromboembolism, or in-stent thrombosis) occurred in 13% (n=26) of all patients independently of ASA and clopidogrel non-responsiveness as assessed by both devices.ConclusionsOur results show that LTA and PFA-100® are not interchangeable in the assessment of ASA and clopidogrel non-responsiveness in patients undergoing neuroendovascular interventions.

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