Platelet aggregation in response to ADP is highly variable in normal donors and patients on anti-platelet medication

2016 ◽  
Vol 54 (7) ◽  
Author(s):  
Eimear Dunne ◽  
Karl Egan ◽  
Siobhán McFadden ◽  
David Foley ◽  
Dermot Kenny
Keyword(s):  
Platelet Aggregation ◽  
Therapeutic Response ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
P2y12 Inhibitors ◽  
Aggregation Response ◽  
Healthy Donors ◽  
Percutaneous Coronary ◽  
Light Transmission Aggregometry

AbstractP2Y12 inhibitors are indicated in patients following percutaneous coronary intervention. Several studies have demonstrated that high on treatment platelet reactivity is correlated with outcomes yet prospective studies of guided therapy have failed to show benefit. There is a paucity of studies on the platelet aggregation response to ADP before P2Y12 therapy is started. The aim of this study was to characterize platelet responses to 20 μM ADP by light transmission aggregometry (LTA) in a homogenous population.Platelet aggregation was assessed in 201 patients on dual antiplatelet therapy, 98 patients on aspirin alone and 47 normal, healthy volunteers free from anti-platelet medication.Consensus guidelines suggest that a platelet aggregation response in response to the agonist ADP of <57% is an adequate therapeutic response to P2Y12 inhibition. Seven healthy donors and 38 patients taking aspirin only had aggregation responses below 57%.The results of our study demonstrate that 15% of normal donors and 38% of patients taking aspirin only would be classified as having a therapeutic response to P2Y12 inhibition using current guidelines.

scholarly journals On-treatment platelet reactivity in the era of new ADP receptor blockers: data from a real-world clinical practice

2018 ◽  
Vol 18 (2) ◽  
pp. 34-39
Author(s):  
I Skornova ◽  
M Samos ◽  
R Simonova ◽  
J Zolkova ◽  
L Stanciakova ◽  
...  
Keyword(s):  
Light Transmission ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Reactivity Index ◽  
Percutaneous Coronary ◽  
Light Transmission Aggregometry ◽  
Receptor Blockers ◽  
St Elevation ◽  
Adp Receptor ◽  
A Prospective Study

Abstract Objectives: Several studies have questioned the need for platelet function testing in patients treated with new ADP receptor blockers (ADPRB). The aim of this study was to evaluate the prevalence of high on-treatment platelet reactivity (HTPR) among acute ST-elevation myocardial infarction (STEMI) patients treated with newer ADPRB. Methods: A prospective study enrolling 44 acute previously ADPRB naive STEMI patients (31 men, 13 women) undergoing primary percutaneous coronary intervention (pPCI) was performed. Among the studied population 23 patients received prasugrel and 21 patients received ticagrelor. Antiplatelet response was tested with light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) flow cytometry assay. Samples were taken prior to coronary angiography (sample 1) and on the day after this procedure (sample 2). Results: The mean platelet aggregation after induction with ADP was 51.7 ± 24.8% in sample 1 and 25.3 ± 20.1% in sample 2. An examination of VASP-P showed a mean platelet reactivity index of 56.8 ± 25.7% in sample 1 and 23.8 ± 23.1% in sample 2, respectively. The study identified 11.4% of patients in sample 2 as ADP receptor blocker non-responders. No significant differences were found between prasugrel-treated to ticagrelor-treated patients. Conclusions: This pilot study demonstrated HTPR among acute STEMI patients treated with newer ADPRB.

scholarly journals Comparison of Light Transmission Aggregometry With Impedance Aggregometry in Patients on Potent P2Y12 Inhibitors

2020 ◽  
pp. 107424842096870
Author(s):  
Patricia P. Wadowski ◽  
Joseph Pultar ◽  
Constantin Weikert ◽  
Beate Eichelberger ◽  
Irene M. Lang ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Multiple Electrode Aggregometry ◽  
Impedance Aggregometry ◽  
Light Transmission Aggregometry ◽  
Sensitivity Specificity

Since data on the agreement between light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) in patients on the more potent P2Y12 inhibitors are missing so far, we investigated if the evaluation of the responsiveness to therapy by LTA can be replaced by MEA in 160 acute coronary syndrome (ACS) patients on dual antiplatelet therapy with aspirin and prasugrel or ticagrelor (n = 80 each). Cut-off values for high on-treatment residual platelet reactivity (HRPR) in response to adenosine diphosphate (ADP) or arachidonic acid (AA) were defined according to previous studies showing an association of HRPR with the occurrence of adverse ischemic outcomes. ADP- inducible platelet aggregation was 33% and 37% (p = 0.07) by LTA and 19 AU and 20 AU (p = 0.38) by MEA in prasugrel- and ticagrelor-treated patients, respectively. AA- inducible platelet aggregation was 2% and 3% by LTA and 15 AU and 16 AU by MEA, (all p ≥ 0.3) in patients on prasugrel and ticagrelor, respectively. By LTA, HRPR ADP and HRPR AA were seen in 5%/5% and in 4%/ 13% of patients receiving prasugrel- and ticagrelor, respectively. By MEA, HRPR ADP and HRPR AA were seen in 3%/ 25% and 0%/24% of prasugrel- and ticagrelor-treated patients, respectively. ADP-inducible platelet reactivity by MEA correlated significantly with LTA ADP in prasugrel-treated patients (r = 0.4, p < 0.001), but not in those receiving ticagrelor (r = 0.09, p = 0.45). AA-inducible platelet aggregation by LTA and MEA did not correlate in prasugrel- and ticagrelor-treated patients. Sensitivity/specificity of HRPR by MEA to detect HRPR by LTA were 25%/99% for MEA ADP and 100%/79% for MEA AA in prasugrel-treated patients, and 0%/100% for MEA ADP and 70%/83% for MEA AA in ticagrelor-treated patients. In conclusion, on-treatment residual ADP-inducible platelet reactivity by LTA and MEA shows a significant correlation in prasugrel- but not ticagrelor-treated patients. However, in both groups LTA and MEA revealed heterogeneous results regarding the classification of patients as responders or non-responders to P2Y12 inhibition.

Aspirin I.V. Loading during Elective Percutaneous Coronary Intervention

Pharmacology ◽  
2021 ◽  
pp. 1-5
Author(s):  
David Naguib ◽  
Carolin Helten ◽  
Saif Zako ◽  
Philipp Mourikis ◽  
René M’Pembele ◽  
...  
Keyword(s):  
Pilot Study ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Bleeding Complications ◽  
Loading Dose ◽  
Bleeding Events ◽  
Elective Percutaneous Coronary Intervention ◽  
Percutaneous Coronary ◽  
The Impact

Additional loading dose of acetylsalicylic acid (ASA) during percutaneous coronary interventions (PCIs) despite permanent oral ASA medication is frequently applicated. The impact on platelet reactivity and clinical events is not known. In this pilot study, we aimed to analyze high on-treatment platelet reactivity (HTPR) to aspirin in patients undergoing elective PCI. Platelet reactivity was measured using light-transmission aggregometry in 100 patients on permanent low-dose ASA medication undergoing elective PCI. Platelet reactivity measured by arachidonic acid-induced maximum of aggregation (MoA) in patients with versus without additional peri-procedural ASA loading (500 mg i.v.) was compared. HTPR was defined as MoA &#x3e;20% for ASA. Major adverse cerebro- and cardiovascular events (MACCEs) and bleeding events were evaluated during hospital course. HTPR rate was similar in both groups (HTPR to ASA: loading vs. control 6% vs. 16%, odds ratio [OR] = 0.33, 95% confidence interval [CI] 0.08–1.35, <i>p</i> = 0.12). In-hospital MACCEs were not different between groups (MACCE: loading vs. control: 0 vs. 0 patient, OR = 1.32, 95% CI 0.03–67.95, <i>p</i> = 0.89). Thrombolysis in myocardial infarction minimal bleedings were numerically higher in patients without ASA loading dose. In this pharmacodynamic pilot study, additional ASA loading did not reduce HTPR to ASA. Furthermore, ASA loading did not increase in-hospital MACCE and bleeding complications.

Clopidogrel pretreatment in primary percutaneous coronary intervention: Prevalence of high on-treatment platelet reactivity and impact on preprocedural patency of the infarct-related artery

2013 ◽  
Vol 110 (07) ◽  
pp. 110-117 ◽  
Author(s):  
Javier Berdejo ◽  
Gerard Roura ◽  
Josep Gómez-Lara ◽  
Rafael Romaguera ◽  
Luis Teruel ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Primary Percutaneous Coronary Intervention ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Poor Response ◽  
Antiplatelet Agents ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Percutaneous Coronary ◽  
Infarct Related Artery

SummaryTo date, there is limited data on levels of platelet inhibition achieved in patients with ST-elevation myocardial infarction (STEMI) who are loaded with clopidogrel and aspirin (ASA) prior to undergoing primary percutaneous coronary intervention (P-PCI). The aim of this investigation was to evaluate the percentage of STEMI patients with high on-treatment platelet reactivity (HPR) to clopidogrel at the time of initiating P-PCI and its association with the initial patency of the infarct-related artery (IRA). This prospective pharmacodynamic study included 50 STEMI patients, previously naïve to oral antiplatelet agents, who received 500-mg ASA and 600-mg clopidogrel loading doses prior to P-PCI. Platelet function assessment was performed at the beginning of the procedure using various assays, including VerifyNow™ system (primary endpoint), light transmission aggregometry and multiple electrode aggregometry. The percentage of patients with suboptimal response to clopidogrel and ASA assessed with the VerifyNow™ system was 88.0% and 28.6%, respectively. Similar results were obtained with the other assays used. A higher percentage of patients with initial patency of the IRA was observed among those patients without HPR compared with those with HPR to clopidogrel (66.7% vs 15.9%; p=0.013), while no differences were observed regarding postprocedural angiographic or electrocardiographic outcomes. In conclusion, this study shows that a high percentage of STEMI patients have inadequate levels of clopidogrel-induced and, to a lesser extent, aspirin-mediated platelet inhibition when starting a P-PCI procedure, and suggests that a poor response to clopidogrel might be associated with impaired initial TIMI flow in the IRA.

scholarly journals Protease-Activated Receptor-Mediated Platelet Aggregation In Patients With Type 2 Diabetes On Potent P2Y12 Inhibitors

2021 ◽  
Author(s):  
Benjamin Panzer ◽  
Patricia P Wadowski ◽  
Kurt Huber ◽  
Simon Panzer ◽  
Thomas Gremmel
Keyword(s):  
Type 2 Diabetes ◽  
Platelet Aggregation ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
The Body ◽  
Diabetic Patients ◽  
P2y12 Inhibitors ◽  
Platelet Aggregometry

Abstract Background: Dual antiplatelet therapy is a cornerstone in the secondary prevention of ischemic events following percutaneous coronary intervention (PCI) with stent implantation. The new, more potent adenosine diphosphate (ADP) P2Y12 receptor inhibitors prasugrel and ticagrelor have been shown to improve patients’ outcomes. Whether or not these drugs have equal efficacy in diabetic as in non-diabetic individuals is disputed. Furthermore, platelets can be activated by thrombin, which is, at least in part, independent of ADP-inducible activation. Protease-activated receptor (PAR)-1 and -4 are thrombin receptors on human platelets activated by the agonists SFLLRN and AYPGKF, respectively. In the current study, we sought to compare the in vitro efficacy of prasugrel (n=121) and ticagrelor (n=99) to inhibit PAR-mediated platelet activation in patients with type 2 diabetes (n=55).Materials and Methods: We compared P2Y12-, PAR-1- and PAR-4-mediated platelet aggregation as assessed by multiple electrode platelet aggregometry between prasugrel- and ticagrelor-treated patients without and with type 2 diabetes who underwent acute PCI. Results: There were no significant differences of on-treatment platelet aggregation in response to ADP, SFLLRN and AYPGKF between patients on prasugrel or on ticagrelor. Diabetic and non-diabetic patients responded equally. There was no significant correlation between either; ADP-, SFLLRN-, or AYPGKF-inducible platelet aggregation and levels of HbA1c or the body mass index. However, we observed patients with high residual platelet reactivity to SFLLRN and AYPGKF in all cohorts.Conclusion: Prasugrel and ticagrelor inhibit platelet aggregation in diabetic and non-diabetic patients to a similar extent.

Predictive Value of Methods Measuring Platelet Activation for Ischemic Events in Patients Receiving Clopidogrel: A Systematic Review and Meta-analysis

2019 ◽  
Vol 24 (44) ◽  
pp. 5313-5333 ◽  
Author(s):  
Zhe Wang ◽  
Qiufen Xie ◽  
Qian Xiang ◽  
Yanjun Gong ◽  
Jie Jiang ◽  
...  
Keyword(s):  
Predictive Value ◽  
Light Transmission ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Clinical Events ◽  
Percutaneous Coronary ◽  
Light Transmission Aggregometry ◽  
Ischemic Events ◽  
Higher Sensitivity

This study investigates the efficiency and predictive value of light-transmission aggregometry (LTA), vasodilator-stimulated phosphoprotein (VASP) and VerifyNow for ischemia in patients undergoing percutaneous coronary intervention (PCI). Studies that used LTA, VASP or VerifyNow to predict ischemia were included, and their quality and efficiency were analyzed using Review Manager 5.3. The sensitivity and specificity of subgroup studies based on the outcome, cut-off value, and follow-up days were calculated and the summary ROC (sROC) curves were compared after having been fitted. Thirty-one studies including a total of 17,314 participants were analyzed. LTA, VASP and VerifyNow presented a considerable efficiency in predicting ischemic clinical events. In the subgroup analysis, the sensitivities of LTA, VASP and VerifyNow in predicting cardiac death, all-cause death, myocardial infarction, stent thrombosis, stroke, and revascularization were 0.40/0.63/0.62, 0.47/0.56/0.39, 0.40/0.48/0.60, 0.44/0.58/0.70, 0.29/not applicable/0.60 and 0.44/0.57/0.37, respectively and the specificities of LTA, VASP, and VerifyNow were 0.85/0.48/0.63, 0.73/0.52/0.63, 0.74/0.55/0.64, 0.75/0.47/0.61, 0.72/not applicable/ 0.61, and 0.70/0.47/0.67, respectively. LTA showed a higher sensitivity in predicting the outcomes over six months than those within six months, while VerifyNow prediction sensitivity was found to be higher within six months. Meanwhile, VerifyNow showed no statistically significant higher AUC of sROC in comparison to LTA and VASP in predicting ischemic events in patients undergoing clopidogrel treatment. The cut-off values of LTA, VASP and VerifyNow were suggested to be 56%, 50% and 235 respectively according to our study.

Abstract 4017: Reduced Anti-Platelet Response to Clopidogrel in Diabetic Patients Undergoing Percutaneous Coronary Intervention

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jorge Saucedo ◽  
Anand Singla ◽  
Karin Mauer ◽  
Kevin P Bliden ◽  
Mark J Antonino ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Platelet Aggregation ◽  
Light Transmission ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Aspirin Resistance ◽  
Diabetic Patients ◽  
Loading Dose ◽  
Platelet Response ◽  
Percutaneous Coronary

Despite dual antiplatelet therapy with aspirin and clopidogrel, patients with diabetes mellitus (DM) suffer from frequent recurrent ischemic events. Previous studies have shown that DM patients have a higher prevalence of aspirin resistance than non-DM patients. The aim of this analysis was to determine if DM patients have a decreased antiplatelet response to either maintenance or high loading clopidogrel administration when compared to non-DM patients. One hundred and thirty eight patients that underwent percutaneous coronary intervention (PCI) in the Clear Platelets-2 Study were included in this analysis. Patients were grouped according to clopidogrel dose use and presence of DM. Subjects were either on maintenance therapy with 75mg of clopidogrel (C75 group; n=72) or received a loading dose of 600mg of clopidogrel immediately after PCI (C600 group; n=66). All patients received 325-mg aspirin. Platelet function was measured by Light Transmission Aggregometry using ADP (5 and 20μM), TRAP (15 μM), and collagen (2μg/ml). Overall, DM patients in the C75 group had higher platelet aggregation using 5 and 20μM ADP and 2μg/ml collagen. DM patients had lower relative platelet inhibition at 24hrs with 5 μM ADP and 2μg/ml collagen in the C600 group when compared to non-DM patients (Table ). DM patients undergoing PCI exhibit higher platelet aggregation when receiving standard clopidogrel maintenance dose and lower relative platelet inhibition with high clopidogrel loading dose. Higher doses of clopidogrel or more potent P2Y12 receptor antagonists may be needed in DM patients to obtain comparable platelet inhibition to non-DM patients.

Association between inflammatory biomarkers and platelet aggregation in patients under chronic clopidogrel treatment

2010 ◽  
Vol 104 (12) ◽  
pp. 1193-1200 ◽  
Author(s):  
Isabell Bernlochner ◽  
Steven Steinhubl ◽  
Siegmund Braun ◽  
Tanja Morath ◽  
Juliane Jaitner ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Primary Outcome Measure ◽  
Reactive Protein ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
Inflammatory Processes ◽  
Independent Association ◽  
Wbc Count

SummaryInflammatory processes in the vessel wall are associated with progression of atherosclerosis and myocardial infarction. Both high levels of C-reactive protein (CRP) and high on-clopidogrel treatment platelet reactivity (HPR) have been linked to an increased risk of ischaemic events after percutaneous coronary intervention (PCI). The aim of this study was to explore the association between biomarker levels of inflammation and platelet reactivity. Stable patients (n=1,223) eligible for this study were under chronic antiplatelet treatment with aspirin and clopidogrel due to prior coronary stent placement. ADP-induced platelet aggregation (in AU*min) was measured on a Multiplate analyser. The primary outcome measure of this retrospective study was the ADP-induced platelet aggregation in patients with versus those without elevated CRP levels. Of the patients 15.5% (n=189) showed elevated CRP levels (≥5 mg/l). Platelet aggregation (median [interquartile range]) was significantly higher in patients with elevated CRP levels compared to patients with normal (<5 mg/l) CRP levels (305 [202–504] AU*min vs. 218 [144–384] AU*min; p<0.001). A multivariable linear regression model that adjusted for known predictors of HPR confirmed a significant independent association between elevated CRP levels and high ADP-induced platelet aggregation values (p=0.0002). Elevated WBC count and fibrinogen levels were also associated with higher platelet aggregation values (p<0.001 for both). In conclusion, elevated levels of CRP, WBC count and fibrinogen were significantly associated with high platelet reactivity in patients under chronic clopidogrel treatment. Whether a direct relation between platelets and inflammation exists, as well as the clinical impact of our results, warrants further investigations.

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