Effects of pH and concentration of sodium citrate anticoagulant on platelet aggregation measured by light transmission aggregometry induced by adenosine diphosphate

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.

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Inter-individual variability in clopidogrel inhibition effect on platelet aggregation

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v9ispl1.1404 ◽

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.

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

Thrombosis and Haemostasis ◽

10.1055/s-0039-1692681 ◽

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.

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High Prevalence of Sticky Platelet Syndrome in Patients with Infertility and Pregnancy Loss

Journal of Clinical Medicine ◽

10.3390/jcm8091328 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1328 ◽

Cited By ~ 2

Author(s):

Eray Yagmur ◽

Eva Bast ◽

Anja Susanne Mühlfeld ◽

Alexander Koch ◽

Ralf Weiskirchen ◽

...

Keyword(s):

Platelet Aggregation ◽

Pregnancy Loss ◽

Low Dose ◽

Light Transmission ◽

Previous History ◽

Adenosine Diphosphate ◽

Healthy Controls ◽

Live Births ◽

Aggregation Response ◽

History Of

Platelet hyperaggregability, known as sticky platelet syndrome (SPS), is a prothrombotic disorder that has been increasingly associated with pregnancy loss. In this retrospective study, we aimed to investigate the clinical and diagnostic relevance of SPS in 208 patients with infertility and unexplained pregnancy loss history. We studied 208 patients that had been referred to undergo a dose-dependent platelet aggregation response to adenosine diphosphate and epinephrine using light transmission aggregometry modified by Mammen during an 11-year period. Patients’ platelet aggregation response was compared with platelet function in 29 female healthy controls of fertile age with no previous history of pregnancy loss. We found a prevalence of SPS type II (33.2%) in 208 female patients with infertility and pregnancy loss. ∆-epinephrine-induced platelet aggregation in patients with SPS was significantly decreased (median 7% and range −21 to 43%) compared to patients without SPS (median 59%, range 7–88% and p < 0.0001) and healthy controls (median 57%, range 8–106% and p < 0.0001). The optimum SPS-diagnostic cutoff value for ∆-epinephrine aggregation was ≤32% (sensitivity 95.7%, specificity 95.2%). SPS patients with low-dose acetylsalicylic acid (ASA) therapy (n = 56) showed improved pregnancy outcome (32 pregnancies; live births n = 18 (56%)) compared to SPS patients without low-dose ASA (n = 13) (3 pregnancies; live births n = 1 (33%)). Our study demonstrates the clinical and diagnostic relevance of platelet hyperaggregation in women with infertility and pregnancy loss history. Further studies should investigate the potential of SPS as a novel decisional tool with both diagnostic and clinical implications in infertility and pregnancy loss.

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

Thrombosis Research ◽

10.1016/j.thromres.2009.04.003 ◽

2009 ◽

Vol 124 (5) ◽

pp. 546-553 ◽

Cited By ~ 13

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

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

Thrombosis and Haemostasis ◽

10.1160/th07-07-0478 ◽

2008 ◽

Vol 99 (01) ◽

pp. 121-126 ◽

Cited By ~ 181

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.

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Use of increased concentrations of adenosinediphosphate for high residual platelet reactivity in patients with coronary heart disease

10.18411/lj-02-2021-33 ◽

2021 ◽

Vol 70 (1) ◽

pp. 129-132

Author(s):

O.A. Trubacheva ◽

S.N. Belyaeva ◽

T.E. Suslova ◽

I.V. Petrova

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Platelet Aggregation ◽

Antiplatelet Therapy ◽

Light Transmission ◽

Platelet Reactivity ◽

Platelet Rich Plasma ◽

Adenosine Diphosphate ◽

Transmission Curve ◽

Platelet Suspension

Detection of a tendency to increased thrombosis in patients with coronary heart disease (CHD) is of important prognostic value in the selection of drugs aimed at achieving a persistent antithrombotic effect. The aim of the study was to evaluate the use of elevated ADP inducer concentrations to improve the accuracy of ADP-induced platelet aggregation in patients with coronary heart disease. Material and method. Material and method. We studied 48 patients with CHD who were on continuous double antiplatelet therapy for 6 months (aspirin 75mg and clopidogrel 75mg per day). The aggregation activity of the platelet suspension was studied using the Born method G. in the modification of Gabbasov Z. A. Platelet activity was evaluated by the degree of aggregation of platelet-rich plasma along the light transmission curve under the influence of the inducer adenosine diphosphate (ADP) at a concentration of 2 mmol/l and by its own patented method against the background of additional ADP application. Results. In patients, platelet aggregation decreased to 5-35% (p<0.005) compared to the standard values, which are 50-60%. The values of platelet aggregation with the additional introduction of the inducer of aggregation ADP in a ratio of 2:1 to 2 µmol/l for 1, 2, 3, and 4-minute registration of platelet aggregation, resulted in increased aggregation from 55% to 75% (p<0.001), indicating high residual platelet reactivity on the background of double antiplatelet therapy. Correlations of the degree of aggregation for elevated ADP concentrations with multivessel arterial lesion and dyslipidemia were also found, r=0.86 and r=0.92, respectively. Conclusion. The use of elevated concentrations of adenosine diphosphate in platelet aggregation in patients with ischemic heart disease increases the accuracy of assessing ADP-induced platelet aggregation against the background of dual antiplatelet therapy and contributes to the detection of high residual platelet reactivity.

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TRANSITORY INFLUENCE OF FIBRINOGEN/FIBRIN DEGRADATION PRODUCTS (FDPs) ON PLATELET AGGREGATION

10.1055/s-0038-1644548 ◽

1987 ◽

Author(s):

S D Nelson ◽

A J Moriarty ◽

R Hughes ◽

K Balnave

Keyword(s):

Platelet Aggregation ◽

Sodium Citrate ◽

Degradation Products ◽

Adenosine Diphosphate ◽

Fibrin Degradation Products ◽

Voltage Change ◽

Systemic Thrombolytic Therapy ◽

Platelet Number ◽

Small Cohort ◽

Post Therapy

This paper describes a pilot study to investigate the influence of FDPs on platelet aggregation in a small cohort of patients (N = 12) undergoing systemic thrombolytic therapy with streptokinase (600,000 I.U. or 1,500,000 I.U. delivered over 30 minutes) for acute myocardial infarction.Serial pre- and post-therapy blood samples were anticoagulated with sodium citrate, and whole blood aggregation studies carried out over 24 hours using a Crono-log 540 aggregometer and the standard adenosine diphosphate (ADP), adrenalin (A), collagen (C) and ristocetin (R) aggregating agents.Results, in the form of mean percentage voltage change from baseline voltage change, measured at 8 minutes after addition of aggregant, are presented for the cohort at times in Figure 1. Serial aggregometry tracings for one representative patient are shown in Figure 2.Clearly comparison of the 1 hour and 18 hour results for each aggregating agent shows a variable but consistent return towards baseline (at FDP < 8 μg/ml) as the FDP concentration drops. This implies that, provided the same platelet population is involved, there is no generalised permanent platelet defect consequent on systemic STK therapy. Coulter counter measurements do not indicate the increase in platelet number that would suggest a large influx of new platelets.

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Platelet Aggregation Induced By Formaldehyde

10.1055/s-0038-1653316 ◽

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.

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

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2015-0802 ◽

2016 ◽

Vol 54 (7) ◽

Cited By ~ 2

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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