scholarly journals Monitoring of Clopidogrel Action: Comparison of Methods

2005 ◽  
Vol 51 (6) ◽  
pp. 957-965 ◽  
Author(s):  
Jörg Geiger ◽  
Lino Teichmann ◽  
Ralf Grossmann ◽  
Barsom Aktas ◽  
Udo Steigerwald ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Platelet Function ◽  
Significant Proportion ◽  
Coronary Intervention ◽  
Platelet Response ◽  
Closure Time ◽  
Vasp Phosphorylation ◽  
Function Analyzer ◽  
Potent Drug ◽  
Platelet Function Analyzer

Abstract Background: Clopidogrel is a potent drug for prevention of adverse effects during and after coronary intervention. Increasing experience indicates that a significant proportion of patients do not respond adequately to clopidogrel. Because failure of antiplatelet therapy can have severe consequences, there is need for a reliable assay to quantify the effectiveness of clopidogrel treatment. Methods: Of 24 healthy volunteers admitted to the study, 18 were treated for 1 week with clopidogrel (300-mg loading dose and 75-mg maintenance dose), and 6 with placebo. Platelet function was monitored by 2 assays, based on flow cytometry and enzyme immunoassay, that measure the phosphorylation status of vasodilator-stimulated phosphoprotein (VASP) and by aggregometry, flow cytometry of P-selectin, and the platelet function analyzer at baseline, on days 1–5, and on day 9 of treatment. Results: Aggregometry and VASP phosphorylation revealed a loss of platelet response to ADP within 12 h after clopidogrel intake. The phosphorylation status of VASP correlated with the inhibition of platelet aggregation. In contrast, neither P-selectin expression nor PFA-100 closure time was a clear indicator of clopidogrel effects on platelets. Conclusions: VASP phosphorylation assays are reliable for quantifying clopidogrel effects. Because the VASP assay directly measures the function of the clopidogrel target, the P2Y12 receptor, the assay is selective for clopidogrel effects rather than effects of other platelet inhibitors commonly in use.

The influence of the haematocrit on primary haemostasis in vitro

2005 ◽  
Vol 94 (12) ◽  
pp. 1213-1218 ◽  
Author(s):  
Marco Eugster ◽  
Walter H. Reinhart
Keyword(s):  
Platelet Function ◽  
Type I Collagen ◽  
Inverse Correlation ◽  
Type I ◽  
Membrane Pore ◽  
Closure Time ◽  
Function Analyzer ◽  
Platelet Function Analyzer

SummaryPrimary haemostasis consists of platelet adhesion to subendothelial collagen, their activation and aggregation and finally the formation of a platelet plug. Erythrocytes are involved in this process because they flow in the center of the vessel and push platelets towards the site of action on the vessel wall and enhance shear forces, which activate platelets. In the platelet function analyzer PFA-100® (Dade Behring, Düdingen, Switzerland), the in vivo situation is simulated in vitro with blood being aspirated at high shear rates (5000s-1) through a capillary into a membrane pore with a diameter of 150 μm coated with type I collagen and either epinephrine or adenosine diphosphate. Aggregating platelets plug the pore and stop the flow, which is measured as the closure time. We analysed the influence of erythrocytes on platelet function analyzer measurements by systematic variation of the haematocrit (20,30,40,and 50%) at constant platelet counts of 289±61 ×103/μl plasma, or 152±30 ×103/μl blood, 96±9 ×103/μl blood and 54±5 ×103/μl blood, respectively. An inverse correlation was found between haematocrit and closure time under all circumstances. A decrease of the platelet count by 50 ×103 /μl could be compensated for by a 10% increase in haematocrit. The haematocrit must, therefore, be taken into consideration for the correct interpretation of PFA-100® measurements. Our data also provide a pathophysiological rationale to reduce the risk of bleeding in patients with thrombocytopenia and anaemia by normalizing the haematocrit with erythrocyte transfusions.

scholarly journals The importance of tests applied to evaluate the effectiveness of antiplatelet therapy in patients with recurrent coronary stent thrombosis

2009 ◽  
Vol 66 (4) ◽  
pp. 328-332
Author(s):  
Aleksandra Grdinic ◽  
Danilo Vojvodic ◽  
Vesna Ilic ◽  
Zvonko Magic ◽  
Nina Djukanovic ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Stent Thrombosis ◽  
Platelet Function ◽  
Coronary Intervention ◽  
P2y12 Receptor ◽  
Cardiac Events ◽  
Major Haplotype ◽  
Function Analyzer ◽  
Insufficient Response ◽  
Platelet Function Analyzer

Background. Stent thrombosis is potentially lethal complication with huge economic burden. The role of insufficient response to antiplatelet therapy is still unclear reason for its occurrence. Case report. We presented 54-year-old man with recurrent stent thrombosis on the 4th, 9th and 12th day after the primary percutaneous coronary intervention in spite of double antiaggregation therapy (aspirin+ clopidogrel). All possible procedural causes were excluded and reimplantation of intracoronary stent was insufficient to resolve the problem, so four platelet tests were performed: flow cytometry, Platelet Function Analyzer-100 test, aggregometry, and determination of gene polymorphism for P2Y12 receptor (directly involved in the mechanism of thienopyridine), and GPIIbIIIa receptor (final receptor in aggregation). The patient was the carrier of the major haplotype H1H1 for P2Y12 receptor and minor A1A2 for GPIIbIIIa receptor. The results of all the performed tests showed insufficient antiplatelet effect of aspirin and sufficient response to thienopyridin (not to clopidogrel, but to ticlopidine). Conclusion. Performance of platelet function tests is necessary in the case of major adverse cardiac events especially stent thrombosis, after implantation of intracoronary stent.

Platelet function in cats with hyperthyroidism

2020 ◽  
Vol 22 (12) ◽  
pp. 1214-1218
Author(s):  
Elizabeth C Hiebert ◽  
David L Panciera ◽  
Katie M Boes ◽  
Lara Bartl
Keyword(s):  
Platelet Count ◽  
Platelet Function ◽  
Adenosine Diphosphate ◽  
Control Group ◽  
Closure Time ◽  
Function Analyzer ◽  
The Mean ◽  
Platelet Function Analyzer ◽  
Von Willebrand ◽  
Willebrand Factor

Objectives Cats with hyperthyroidism have been reported to develop thromboembolism, with and without echocardiographic abnormalities consistent with hyperthyroidism. The objective of this study was to compare platelet function in cats with hyperthyroidism with euthyroid age-matched cats. We hypothesized that cats with hyperthyroidism have shortened collagen and adenosine diphosphate (C-ADP) closure times as measured with the platelet function analyzer (PFA-100) in comparison with healthy, age-matched controls. Methods Sixteen hyperthyroid and nine euthyroid healthy cats >7 years of age were recruited from the hospital population. Platelet function, measured using the C-ADP closure times by the PFA-100, and platelet count were measured in healthy euthyroid cats and cats with hyperthyroidism. Results Mean ± SD closure times were not significantly different between control (66.3 ± 9.6 s) and hyperthyroid cats (65.9 ± 11.5 s; P = 0.75). The mean ± SD closure times of hyperthyroid cats that either were untreated or received methimazole for ⩽3 weeks (n = 6; mean 68.5 ± 15.4 s) was not different than that of cats treated for >3 weeks (n = 10; mean 64.3 ± 8.9 s; P = 0.57). The mean automated platelet count was higher in the hyperthyroid group than in the control group ( P = 0.023). Conclusions and relevance Platelet function, as measured by closure time under high shear conditions using C-ADP as an agonist, was not affected by hyperthyroidism in this group of cats. Further research is needed to determine if a hypercoagulable state exists in hyperthyroid cats and the potential roles platelets and von Willebrand factor may have.

Comparison of current platelet functional tests for the assessment of aspirin and clopidogrel response

2016 ◽  
Vol 116 (10) ◽  
pp. 638-650 ◽  
Author(s):  
Jean-Claude Bordet ◽  
Claude Negrier ◽  
Yesim Dargaud ◽  
Sandra Le Quellec
Keyword(s):  
Platelet Function ◽  
Light Transmission ◽  
Platelet Response ◽  
Platelet Function Tests ◽  
Clopidogrel Resistance ◽  
Function Tests ◽  
Function Analyzer ◽  
Clopidogrel Therapy ◽  
Whole Blood Aggregometry ◽  
Platelet Function Analyzer

SummaryThe two most widely used antiplatelet drugs in the world are aspirin and clopidogrel. However, some patients on aspirin and/or clopidogrel therapy do not respond appropriately to either aspirin or clopidogrel. This phenomenon is usually called “aspirin/clopidogrel resistance”. Several platelet function tests have been used in various studies for the assessment of aspirin and clopidogrel resistance in healthy individuals and patients admitted in cardiology departments. An accurate assessment of platelet response to aspirin/clopidogrel could benefit patients by proposing tailored-antiplatelet therapy based on test results. However, there is a clear lack of standardisation of such techniques and their analytical variability may induce misinterpretation. After a quick report of the mechanisms responsible for aspirin/clopidogrel resistance, we describe the pre-analytical aspects and the analytical performances of current platelet function tests (Light-transmission aggregometry, whole-blood aggregometry, VerifyNow®, Platelet Function Analyzer®, thromboelastography, VASP assay) that are used for the assessment of aspirin/clopidogrel resistance in clinical studies. Considering the different variables that have to be taken into account with each of the platelet function tests, a particular attention should be paid when interpreting results.

Cross validation of the Multiple Electrode Aggregometry

2009 ◽  
Vol 102 (08) ◽  
pp. 397-403 ◽  
Author(s):  
Jolanta Siller-Matula ◽  
Ghazaleh Gouya ◽  
Michael Wolzt ◽  
Bernd Jilma
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Cross Validation ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Multiple Electrode Aggregometry ◽  
Vasp Phosphorylation ◽  
Function Analyzer ◽  
Platelet Function Analyzer ◽  
Multiple Electrode

SummarySeveral test systems exist for assessment of platelet function in patients under clopidogrel or aspirin therapy. The objective was to cross-validate the Multiple Electrode Aggregometry (MEA) with three other methods used for determining platelet reactivity under treatment with clopidogrel and aspirin. Platelet function was assessed by the MEA, Vasodilator Stimulated Phosphoprotein (VASP) phosphorylation assay, Platelet Function Analyzer-100 (PFA-100) and the Cone and Platelet Analyzer. Measurements were performed in blood from nine healthy volunteers at baseline, 2, 4, 6 and 72 hours after clopidogrel and aspirin loading. The apparent effect size for clopidogrel and aspirin was greatest for the MEA: treatment induced a 19-fold difference in the arachidonic acid-induced platelet aggregation and an 11-fold difference in the adenosine diphosphate-induced platelet aggregation before/after treatment. For comparison, aspirin and clopidogrel induced only 2.0– to 2.6 -fold changes in other tests (VASP assay, Cone and Platelet Analyzer and PFA-100). Maximal effects were seen 2 hours after aspirin loading and shorter than 72 hours after clopidogrel loading. In conclusion, aspirin and clopidogrel produce stronger signals in the MEA compared to several other methods.

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