miR-34b-3p May Promote Antiplatelet Efficiency of Aspirin by Inhibiting Thromboxane Synthase Expression

2019 ◽  
Vol 119 (09) ◽  
pp. 1451-1460
Author(s):  
Wen Wen Liu ◽  
Hao Wang ◽  
Xia Huan Chen ◽  
Sidney W. Fu ◽  
Mei Lin Liu
Keyword(s):  
Platelet Aggregation ◽  
Bioinformatics Analysis ◽  
Light Transmission ◽  
Lower Quartile ◽  
Thromboxane Synthase ◽  
Gene Profiles ◽  
Light Transmission Aggregometry ◽  
Cell Proliferation Inhibition ◽  
Human Blood Samples ◽  
Artery Disease

AbstractAspirin has been widely used for the prevention of cardiovascular diseases, but its antiplatelet efficiency varies between individuals. The present study aimed to evaluate response to aspirin based on gene profiles as well as potential regulating pathways using human blood samples and cell lines. Platelet function in patients 50 years or older with coronary artery disease on 100 mg/day aspirin was measured by light transmission aggregometry (LTA) of arachidonic acid (AA)-induced platelet aggregation. The expression of eight candidate genes—PTGS1/COX1, PLA2G4A, PLA2G6, PLA2G7, TBXAS1, TBXA2R, PTGIR, and ITGA2B—and the ingredients involved in AA metabolism were analyzed. Our data showed that the expressions of thromboxane A synthase 1 (TBXAS1), thromboxane synthase (TXS), and thromboxane B2 (TXB2) were increased in the upper quartile of platelet aggregation (LTA-AA_Q4) group compared with the lower quartile of platelet aggregation (LTA-AA_Q1) group. Our bioinformatics analysis suggested that TBXAS1 was targeted by miR-34b-3p via binding to its 3′-UTR, which was subsequently verified experimentally. Although overexpression of miR-34b-3p exhibited no apparent effect on cell proliferation, inhibition of miR-34b-3p promoted megakaryocyte viability. Our data demonstrated that the expression of TBXAS1 was higher in the aspirin hyporesponsiveness group than that in the hyperresponsiveness group, suggesting that high expression of TBXAS1 may be associated with aspirin hyporesponsiveness. miR-34b-3p may regulate the platelet and aspirin response by suppressing TBXAS1 expression and megakaryocyte proliferation.

Inter-individual variability in clopidogrel inhibition effect on platelet aggregation

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Hussein Ali Sahib ◽  
Bassim Irhiem Mohammed ◽  
Ban A. Abdul Majid
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Aggregation ◽  
Coronary Care Unit ◽  
Light Transmission ◽  
Individual Variability ◽  
Study Group ◽  
Inhibition Effect ◽  
Light Transmission Aggregometry ◽  
Coronary Care ◽  
Skewness And Kurtosis

Despite the unmistakable beneficial effect of clopidogrel on platelet aggregation,still there are some patient poorly responds to clopidogrel that may lead to worse cardiovascular clinical events.One hundred and twenty seven patients with cardiovascular disease (ACS,stroke,or TIA) were enrolled as a study group. Patients were recruited at coronary care unit (CCU) of Al-Yarmouk Teaching Hospital. Paletlet assessment was done by using light transmission aggregometry. between the patients that enrolled in this study there are significant inter-individual variability both skewness and Kurtosis were negative (-0.450,-0.130) respectively. 24% of patient enrolled in this study were hyporesponder.

Malondialdehyde Assay in the Evaluation of Aspirin Antiplatelet Effects

Pharmacology ◽  
2018 ◽  
Vol 103 (1-2) ◽  
pp. 23-29 ◽  
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.

Insights into the interpretation of light transmission aggregometry for evaluation of platelet aggregation inhibition by clopidogrel

2009 ◽  
Vol 124 (5) ◽  
pp. 546-553 ◽  
Author(s):  
Marie Lordkipanidzé ◽  
Chantal Pharand ◽  
Donald A. Palisaitis ◽  
Erick Schampaert ◽  
Jean G. Diodati
Keyword(s):  
Platelet Aggregation ◽  
Light Transmission ◽  
Platelet Aggregation Inhibition ◽  
Light Transmission Aggregometry ◽  
Aggregation Inhibition

Assessment of ADP-induced platelet aggregation with light transmission aggregometry and multiple electrode platelet aggregometry before and after clopidogrel treatment

2008 ◽  
Vol 99 (01) ◽  
pp. 121-126 ◽  
Author(s):  
Siegmund Braun ◽  
Stefan Jawansky ◽  
Wolfgang Vogt ◽  
Julinda Mehilli ◽  
Albert Schömig ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Whole Blood ◽  
Light Transmission ◽  
Platelet Rich Plasma ◽  
Platelet Aggregometry ◽  
Light Transmission Aggregometry ◽  
Before And After ◽  
Standardized Method ◽  
Multiple Electrode

SummaryThe level of platelet aggregation, measured with light transmission aggregometry (LTA) in platelet rich plasma (PRP), has been shown to predict outcomes after percutaneous coronary intervention (PCI). However, measuring parameters of platelet function with LTA is time consuming and weakly standardized. Thus, a fast and standardized method to assess platelet function after clopidogrel treatment would be of great value for clinical practice. A new method, multiple electrode platelet aggregometry (MEA), to rapidly measure platelet aggregation in whole blood has recently been developed. The aim of this study was to assess parameters of platelet function with MEA and LTA before and after administration of 600 mg clopidogrel. Blood samples from 149 patients scheduled for coronary angiography were taken after clopidogrel treatment; in addition, in 60 of the patients samples were available before clopidogrel treatment. ADP-induced platelet aggregation was measured with LTA and simultaneously in whole blood with MEA on the Multiplate analyzer. Platelet aggregation measured with MEA decreased significantly after clopidogrel treatment (P<0.0001). ADP-induced platelet aggregation assessed with MEA and LTA correlated significantly (Spearman rank correlation coefficient=0.71; P<0.0001).The results of MEA, a fast and standardized method to assess the platelet response to ADP prior to and after clopidogrel treatment, correlate well with LTA.

scholarly journals Ticagrelor as an Alternative Antiplatelet Therapy in Cardiac Patients Non-Sensitive to Aspirin

Medicina ◽  
2020 ◽  
Vol 56 (10) ◽  
pp. 519
Author(s):  
Hamzah Khan ◽  
Reid Gallant ◽  
Shubha Jain ◽  
Mohammed Al-Omran ◽  
Charles De Mestral ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Antiplatelet Therapy ◽  
Light Transmission ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Alternative Therapy ◽  
Promising Alternative ◽  
Patients At Risk ◽  
Artery Disease

Background and Objectives: Aspirin (acetylsalicylic acid—ASA) is a first-line antiplatelet therapy provided to patients with coronary artery disease (CAD). However, it has been demonstrated that 20–30% of these patients are non-sensitive to their ASA therapy. ASA non-sensitivity is a phenomenon where low-dose ASA (81–325 mg) does not completely inhibit arachidonic-acid-induced platelet aggregation, putting patients at risk of adverse cardio-thrombotic events. Ticagrelor is a P2Y12 receptor inhibitor and alternative antiplatelet that has been approved to reduce the risk of stroke, myocardial infarction, and overall cardiovascular-related death. In this study, we aimed to identify ASA non-sensitive patients and evaluate if they would be sensitive to ticagrelor. Materials and Methods: For this pilot study, thirty-eight patients with CAD taking 81 mg ASA were recruited. Blood samples were collected from each patient and platelet rich plasma (PRP) from each sample was isolated. Light-transmission aggregometry (LTA) was used to determine baseline ASA sensitivity in each patient using 0.5 mg/mL arachidonic acid as a platelet agonist. Patients with ≥20% maximal platelet aggregation after activation were considered ASA non-sensitive. Fresh PRP samples from all patients were then spiked with a clinical dosage of ticagrelor (3 μM—approximately equivalent to a loading dose of 180 mg ticagrelor). Sensitivity was determined using LTA and 5 μM ADP as a platelet agonist. Patients with ≥46% maximal platelet aggregation were considered ticagrelor non-sensitive. Results: Of the 38 CAD patients taking 81 mg ASA, 32% (12/38) were non-sensitive to their 81 mg ASA therapy. All 38 of the recruited patients (100%) were sensitive to ticagrelor ex vivo. In conclusion, we were able to identify ASA non-sensitivity using LTA and determine that ASA non-sensitive patients were sensitive to ticagrelor. Conclusions: Our results suggest that ticagrelor is a promising alternative therapy for patients who are non-sensitive to ASA.

scholarly journals Platelet-to-lymphocyte and Neutrophil-to-lymphocyte Ratios Predict Target Vessel Restenosis after Infrainguinal Angioplasty with Stent Implantation

2020 ◽  
Vol 9 (6) ◽  
pp. 1729 ◽  
Author(s):  
Silvia Lee ◽  
Timothy Hoberstorfer ◽  
Patricia P. Wadowski ◽  
Christoph W. Kopp ◽  
Simon Panzer ◽  
...  
Keyword(s):  
Stent Implantation ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Limb Ischemia ◽  
Target Vessel ◽  
Light Transmission Aggregometry ◽  
Platelet Aggregate ◽  
Artery Disease ◽  
Underlying Mechanisms ◽  
Angioplasty And Stenting

Platelet-to-lymphocyte (PLR), neutrophil-to-lymphocyte (NLR) and lymphocyte-to-monocyte (LMR) ratios are associated with the occurrence of critical limb ischemia in peripheral artery disease (PAD). We therefore investigated whether PLR, NLR or LMR are linked to target vessel restenosis (TVR) following infrainguinal angioplasty and stenting. Moreover, we studied on-treatment platelet reactivity and neutrophil-platelet aggregate (NPA) formation as potential underlying mechanisms. Platelet, neutrophil, lymphocyte and monocyte counts were determined one day after angioplasty and stenting in 95 stable PAD patients. Platelet reactivity and NPA formation in response to protease-activated receptor−1 stimulation were measured by light transmission aggregometry (LTA) and flow cytometry, respectively. PLR and NLR were significantly higher in patients who subsequently developed TVR (both p < 0.05). In contrast, LMR did not differ significantly between patients without and with TVR (p = 0.28). A PLR ≥ 91 and NLR ≥2.75 were identified as the best thresholds to predict TVR, providing sensitivities of 87.5% and 81.3%, and specificities of 34.9% and 50.8%, respectively, and were therefore defined as high PLR and high NLR. TVR occurred significantly more often in patients with high PLR and high NLR than in those with lower ratios (both p < 0.05). Patients with high PLR and high NLR exhibited significantly increased on-treatment platelet aggregation compared to those with lower ratios, and patients with high PLR had higher levels of NPA formation (all p < 0.01). In conclusion, PLR and NLR predict TVR after infrainguinal angioplasty with stent implantation. Platelet activation and neutrophil-platelet interaction may be involved in the underlying pathomechanisms

Platelet Aggregation Induced By Formaldehyde

1981 ◽  
Author(s):  
J A Zeller ◽  
K Eurenius ◽  
R E Dayhoff ◽  
R S Ledley ◽  
L S Rotolo
Keyword(s):  
Platelet Aggregation ◽  
Small Volume ◽  
Light Transmission ◽  
Platelet Rich Plasma ◽  
Microscopic Analysis ◽  
Formaldehyde Concentration ◽  
Microscopic Method ◽  
Light Transmission Aggregometry ◽  
Quantitative Image ◽  
Aggregation Analysis

Formaldehyde causes platelet aggregation (or agglutination) which varies with dosage. Aggregation was studied in ten blood samples drawn from normal volunteers. A small volume of formaldehyde was added to platelet rich plasma in a light transmission aggregcmeter to produce final formaldehyde concentrations between 0.1% and 8%. Measurements were made by three methods: (1) light transmission aggregometry, (2) visual semi-quantitative microscopic analysis, and (3) quantitative image analysis (Computerized Platelet Aggregation Analysis) . Using the visual semi-quantitative microscopic method, the dose response curve (expressed as the percentage of platelets involved in aggregates) increased from 11% at a formaldehyde concentration of 0.1% to 41% at a 0.5% formaldehyde concentration; it then decreased to 11% at a formaldehyde concentration of 8%. This curve may reflect the influence of two different formaldehyde effects: an aggregating effect which increases until about 0.5% concentration, whereafter a fixative effect may predominate. Light transmission aggregometry recordings did not provide a reliable indicator of the presence and degree of aggregation. A comparison of the visual semi-quantitative method and CPAA show similar detection of aggregating effects. In sunmary, formaldehyde has an aggregating effect on normal platelets. The physiologic significance of this effect is unknown; however, because formaldehyde is used to process platelets in studies of platelet aggregation, this effect may be of importance.

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.

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