The use of the VerifyNow system to monitor antiplatelet therapy: A review of the current evidence

Department of Cardiology, St Antonius Hospital, Nieuwegein, the Netherlands.
Platelets (Impact Factor: 2.98). 12/2008; 19(7):479-88. DOI: 10.1080/09537100802317918
Source: PubMed


Multiple studies have demonstrated the effectiveness of dual or triple antiplatelet therapy with aspirin, clopidogrel and glycoprotein (GP) IIb/IIIa therapy in patients with acute coronary syndromes as well as in patients undergoing coronary stent implantation. In the last few years, it is becoming clear that not all patients receive the full benefits with the current standard dosages of antiplatelet therapy. Specifically, numerous studies have revealed a wide interindividual variability in the response to these antiplatelet agents and, more importantly, both nonresponsiveness as well as a heightened residual platelet reactivity have been linked to the occurrence of adverse cardiovascular events. Therefore, assays that identify those patients with an impaired responsiveness or a heightened platelet reactivity despite dual antiplatelet therapy may contribute to better risk stratification and will probably improve clinical outcome when appropriate action is initiated. Likewise, a considerable number of patients do not achieve the minimal inhibition of aggregation threshold with the current recommended weight-adjusted dosages of GP IIb/IIIa therapy. Identifying and optimizing the absolute degree of platelet inhibition in this subgroup of patients will probably improve clinical outcome. The VerifyNow platform is one of the most user friendly point-of-care platelet function test systems because it produces rapid results at the patient bedside. The purpose of the present paper is to give insight into the principal mechanisms of the VerifyNow system, to discuss its clinical utility for the monitoring of antiplatelet therapy and to discuss the proposed cut-off levels to segregate responders from non-responders for the different types of antiplatelet therapy.

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    • "The VerifyNow (Accumetrics, San Diego, CA, USA) point-of-care (POC) test has been used in clinical evaluation or monitoring of GPIIb-IIIa or P2Y12 antagonists, particularly in the setting of periprocedural percutaneous coronary intervention (PCI) [Van Werkum et al., 2008]. The test is based on the ability of a drug to inhibit the agglutination and aggregation of fibrinogen-coated beads by activated platelets. "
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    ABSTRACT: Strategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I-III Regulatory, Quality, ManufacturingPostmarketing Phase IV There is an increasing need for the standardization of platelet function and coagulation testing for the assessment of antithrombotic therapies. Investigators continue to strive to identify ideal laboratory testing and monitoring procedures for acquired and inherited platelet function defects as well as for evaluating patient status when treated with existing or emerging antithrombotics. These therapies are used primarily in the treatment of ischemic complications. In patients receiving antithrombotic therapy, the balance between hemostasis and thrombosis is a challenge as there is an ongoing risk for bleeding when patients are receiving antiplatelet agents or anticoagulants to lessen their risk for secondary thrombotic events. There are several diverse tests for monitoring anticoagulant therapy; however, as new agents are developed, more specific tests will be required to directly assess these agents in relationship to overall coagulation status. Research in the platelet biology field is ongoing to provide point-of-care methodologies for the assessment of platelet reactivity in terms of both bleeding and thrombosis risk. Currently there are no instruments that reliably assess the risk of bleeding. The challenges that routinely faced are the complexity of physiology, the need for standardization of platelet testing methodology, and the necessity for appropriate interpretation of the test results.
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    • "The VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) is a whole blood point-of-care test [9], which measures the ADP-induced co-agglutination of platelet and fibrinogen-coated beads in the presence of PGE1. The presence of PGE1 makes the test specific for the P2Y12 receptor pathway. "
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    ABSTRACT: Clinical studies suggest that 10-50% of patients are resistant to clopidogrel therapy. ADP induced platelet aggregation, a widely used test to monitor clopidogrel therapy, is affected by aspirin and is not specific for the P2Y12 receptor inhibited by clopidogrel. To develop a P2Y12-specific platelet aggregation test and to compare it with other methods used for monitoring clopidogrel therapy. Study population included 111 patients with the history of ischemic stroke being on clopidogrel monotherapy and 140 controls. The effect of clopidogrel was tested by a newly developed ADP(PGE1) aggregation test in which prostaglandin E1 treated platelets are used. Results of conventional ADP induced platelet aggregation, VerifyNow P2Y12 assay and ADP(PGE1) aggregation were compared to those obtained by flow cytometric analysis of vasodilator stimulated phosphoprotein (VASP) phosphorylation. Reference intervals for all assays were determined according to the guidelines of Clinical Laboratory Standards Institute. The P2Y12-specificity of ADP(PGE1) test was proven by comparing it with ADP aggregation in the presence of P2Y1 antagonist, adenosine 3', 5'-diphosphate. The method was not influenced by aspirin treatment. Approximately 50% of patients were clopidogrel resistant by conventional ADP aggregation and VerifyNow tests. The ADP(PGE1) method and the VASP phosphorylation assay identified 25.9% and 11.7% of patients as non-responders, respectively. ADP(PGE1) aggregation showed good correlation with VASP phosphorylation and had high diagnostic efficiency. The new ADP(PGE1) method is a reliable test for monitoring P2Y12 receptor inhibition by platelet aggregation. As a subset of patients are non-responders, monitoring clopidogrel therapy by adequate methods is essential.
    Full-text · Article · Jul 2013 · PLoS ONE
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    • "The magnitude of OPR was quantified using the VerifyNow™ system (Accumetrics, Inc., San Diego, CA, USA). The VerifyNow™ system is a whole blood cartridge-based method to determine the magnitude of platelet agglutination induced by either arachidonic acid in the aspirin assay and adenosine diphosphate (ADP) and prostaglandin E1 in P2Y12 assay.16) Platelet reactivity was reported as aspirin reaction units (ARU) and P2Y12 reaction units (PRU) and higher reaction unit reflected higher OPR. "
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    ABSTRACT: Small dense low density lipoproteins (sd-LDL) are a risk factor for coronary artery disease and are known to stimulate platelet function in vitro. This study aimed to evaluate whether high proportion of sd-LDL is associated with high on-treatment platelet reactivity (HOPR). From January 2009 to March 2010, 439 subjects (mean age: 64.3±9.7, Male : Female=306 : 133) were enrolled from the low density LIPOProtein-cholesterol Size measurement Registry with coronary artery disease, who had undergone elective percutaneous coronary intervention and measured both LDL particle size and on-treatment platelet reactivity (OPR). Mean LDL particle size was measured by gradient gel electrophoresis (Quantimetrix, Lipoprint™) and OPR by the VerifyNow™ system (aspirin and P2Y12). Between pattern A (large, buoyant LDL dominant) and B (sd-LDL dominant) population, there were no significant difference in OPR to aspirin (441.3±71.9 vs. 434.07±63.45 aspirin reaction units, p=0.351) or clopidogrel (237.9±87.3 vs. 244.9±80.7 P2Y12 reaction units, p=0.465). There was no difference in LDL particle size between patients with HOPR compared with non-HOPR patients (aspirin: 26.8±0.5 vs. 26.7±0.6 nm, p=0.078, clopidogrel: 26.7±0.6 vs. 26.8±0.5 nm, p=0.857). Pearson's correlation coefficients between LDL particle size and platelet reactivity were not statistically significant (aspirin assay: r=0.080, p=0.098, P2Y12 assay: r=-0.027, p=0.568). There was no significant association between LDL particle size and OPR in patients with coronary artery disease.
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