The Limits of Platelet Function Testing

In the May issue of Clinical Laboratory News, Maggie Yell, MD, and Jeffrey A. Vos, MD, of West Virginia University, describe the advantages and limitations of available platelet function technologies in the setting of antiplatelet therapy. Dual antiplatelet therapies with aspirin and platelet P2Y₁₂ inhibitors serve a number of important functions. They help manage ischemic heart disease following percutaneous coronary intervention (PCI) with coronary artery stents, and may reduce major cardiac events in acute coronary syndrome (ACS). Platelet function assays are charged with predicting ischemic and bleeding risk in patients who take these therapies, but some are limited in what they can do. “Several unique technologies have been devised to assess platelet function by measuring platelet activation and aggregation in response to a variety of agonists,” according to the authors.

Yell and Voss consider the following technologies: the VerifyNow P2Y₁₂ assay; Platelet Function Analyzer-100 (PFA-100); light transmittance aggregometry; vasodilator-stimulated phosphoprotein (VASP) assay; whole blood impedance aggregometry using the Multiplate analyzer with ADP; thromboelastography (TEG) and rotational thromboelastometry (ROTEM) technologies; and PlateletMapping.

Approaches vary in their functionality and efficiency. The VASP assay, which uses whole blood mixed with prostaglandin (PGE1) and ADP incubated at room temperature, can misclassify high numbers of patients with “high on-treatment platelet reactivity” due to its insensitivity to low levels of P2Y₁₂ receptor inhibition. The PFA-100, a rapid point-of-care test, is useful in screening for qualitative platelet defects, but its lack of sensitivity and specificity for the effects of aspirin and P2Y₁₂ inhibitors make it a poor choice for monitoring antiplatelet therapy.

Once the gold standard in platelet function testing, light transmittance aggregometry is no longer used by clinicians to monitor antiplatelet therapy on a daily basis, due to a series of problems that include its high complexity and lack of standardization.

VerifyNow and Multiplate ADP tests are the best choices for monitoring clopidogrel therapy. “However, due to the lack of support by clinical trials, these tests are not currently recommended for routine use in certain situations, such as in low-risk PCI patients and in higher-risk patients transitioning from clopidogrel to potent drugs such as ticagrelor and prasugrel,” Yell and Vos indicate.

Randomized studies on individualized antiplatelet therapy based on platelet function testing are limited in that they tend to enroll patients of low to intermediate risk, and rarely use potent antiplatelet agents.

“Overall, the prognostic value of platelet function testing for risk prediction of ischemic and bleeding events when using P2Y₁₂ receptor inhibitors is well established. Determining a therapeutic window of platelet inhibition should be the primary goal of these assays to help guide the choice of antiplatelet therapy and prevent complications,” Yell and Vos conclude.

Pick up the May CLN to learn more about platelet function testing in patients on antiplatelet therapies.