Various diagnostic and prognostic performance measures have been used to describe the clinical usefulness of platelet function testing in the evaluation and management of patients taking P2Y 12 inhibitors, which reduce the risk for thrombosis due to their action on the platelet P2Y 12 receptor. Platelet function tests are used to confirm the presence of an antiplatelet effect of a P2Y 12 inhibitor, and confirmation that the pharmacodynamic effect is associated with a reduction in the rate of thrombosis. Despite this clear association, enthusiasm for the clinical usefulness of platelet function testing has been tempered based on observed sensitivity, specificity, and positive predictive value for the detection of future thrombotic events. However, evaluating the prognostic utility of a test based on diagnostic performance indicators is not appropriate because prognostic tests are not used to diagnose which patients will have events; instead, they are used to assist in risk stratification. Therefore, when evaluating the usefulness of platelet function testing, diagnostic performance measures such as sensitivity, specificity, and predictive values should focus on diagnostic performance in identifying a pharmacodynamic effect, and prognostic performance should be evaluated using prognostic performance measures such as hazard ratios and net reclassification improvement, which are comparable to other well-established risk factors for cardiovascular events.
"The main issue with these reagents is the elevated risk of adverse bleeding, due to the therapeutics targeting molecular pathways that are important for both thrombotic processes and normal hemostasis.90 This issue is compounded because the assessment of bleeding risk in patients receiving one or more of these therapies is complicated,91,92 generally requiring specialized platelet function analysis where the relationship between platelet function testing and bleeding in different patient groups on combinational therapy is not clear, due to limited data. "
[Show abstract][Hide abstract] ABSTRACT: While platelet activation is essential to maintain blood vessel patency and minimize loss of blood upon injury, untimely or excessive activity can lead to unwanted platelet activation and aggregation. Resultant thrombosis has the potential to block blood vessels, causing myocardial infarction or stroke. To tackle this major cause of mortality, clinical therapies that target platelet responsiveness (antiplatelet therapy) can successfully reduce cardiovascular events, especially in people at higher risk; however, all current antiplatelet therapies carry an increased probability of bleeding. This review will evaluate new and emerging targets for antithrombotics, focusing particularly on platelet glycoprotein VI, as blockade or depletion of this platelet-specific receptor conveys benefits in experimental models of thrombosis and thromboinflammation without causing major bleeding complications.
Hematology Research and Reviews 05/2014; 5:59-68. DOI:10.2147/JBM.S39220
"The most common platelet activation markers assessed by flow cytometry are P-selectin expression on the platelet surface (as a marker of α-granule secretion), the conformational change of GP IIb/IIIa into its active state (measured with monoclonal antibody PAC-1), platelet-leukocyte conjugates, microparticle examination, exposure of anionic, negatively charged phospholipids on the platelet surface (procoagulant activity), and phosphorylation of vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) (BioCytex, Marseille, France), as a marker of P2Y12 receptor activation-dependent signaling [18–20]. Many laboratories have measured a variety of different platelet activation markers and shown that they are elevated in various clinical conditions such as unstable angina, acute myocardial infarction, preeclampsia, peripheral vascular disease, and cerebrovascular ischemia. "
[Show abstract][Hide abstract] ABSTRACT: The major goal of traditional platelet function tests has been to screen and diagnose patients who present with bleeding problems. However, as the central role of platelets implicated in the etiology of arterial thrombotic diseases such as myocardial infarction and stroke became widely known, platelet function tests are now being promoted to monitor the efficacy of antiplatelet drugs and also to potentially identify patients at increased risk of thrombosis. Beyond hemostasis and thrombosis, an increasing number of studies indicate that platelets play an integral role in intercellular communication, are mediators of inflammation, and have immunomodulatory activity. As new potential biomarkers and technologies arrive at the horizon, platelet functions testing appears to take on a new aspect. This review article discusses currently available clinical application of platelet function tests, placing emphasis on essential characteristics.
BioMed Research International 05/2014; 2014(3):456569. DOI:10.1155/2014/456569 · 1.58 Impact Factor
"Clinically, increased on-treatment platelet aggregation is associated with a greater frequency of recurrent thrombotic events while low on-treatment platelet aggregation is associated with increased bleeding risk17-24. Platelet function testing may be used to identify patients with high on-treatment platelet aggregation; however, for logistic and other reasons, use of platelet function testing in clinical care remains controversial18,25-27. "
[Show abstract][Hide abstract] ABSTRACT: Pharmacogenomics, the study of the genomics of drug response and adverse effects, holds great promise for more effective individualized (personalized) medicine. Recent evidence supports a role of loss-of-function (LOF) variants in the cytochrome P450 enzyme CYP2C19 as a determinant of clopidogrel response. Patients given clopidogrel after percutaneous coronary intervention who carry LOF variants do not metabolize clopidogrel, a prodrug, into its active form resulting in decreased inhibition of platelet function and a higher likelihood of recurrent cardiovascular events. Despite a large body of evidence supporting clinical utility, adoption of anti-platelet pharmacogenetics into clinical practice has been slow. In this review, we summarize the pharmacokinetic, pharmacodynamic and clinical evidence, identify gaps in knowledge and other barriers that appear to be slowing adoption, and describe CYP2C19 pharmacogenetics implementation projects currently underway. Only when we surmount these barriers will clinicians be able to use pharmacogenetic information in conjunction with the history, physical examination and other medical tests and information to choose the most efficacious anti-platelet therapy for each individual patient.Journal of Human Genetics advance online publication, 23 May 2013; doi:10.1038/jhg.2013.41.
Journal of Human Genetics 05/2013; 58(6). DOI:10.1038/jhg.2013.41 · 2.46 Impact Factor
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