Evaluating the clinical usefulness of platelet function testing: Considerations for the proper application and interpretation of performance measures

Jeffrey R. Dahlen, PhD, 3985 Sorrento Valley Boulevard, San Diego, CA 92121, USA, Tel.: +1 858 404 8247, Fax: +1 858 875 0602, E-mail: .
Thrombosis and Haemostasis (Impact Factor: 4.98). 12/2012; 109(2). DOI: 10.1160/TH12-08-0608
Source: PubMed


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.

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    • "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. "
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    Hematology Research and Reviews 05/2014; 5:59-68. DOI:10.2147/JBM.S39220
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    • "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. "
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    BioMed Research International 05/2014; 2014(3):456569. DOI:10.1155/2014/456569 · 1.58 Impact Factor
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    • "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. "
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