Integration Of Different Platelet Activity Assays Into A Reproducible Platelet Score

Background: While platelets play a key role in the pathogenesis of atherothrombosis, measuring platelet activity remains a research tool. We sought to 1) develop an integrated platelet score (PS) combining multiple platelet activity measurements, 2) assess its reproducibility over time, 3) investigate its correlation pre- and post-aspirin, and 4) compare subjects with cardiovascular disease (CVD) versus healthy controls. Methods: Following an overnight fast, 48 healthy controls had 4 weekly phlebotomies and received 81 mg aspirin daily between weeks 3 and 4. At each collection, platelet activity was measured using light transmission aggregation (LTA) in response to submaximal epinephrine, ADP, collagen, arachidonic acid (AA) and saline, and whole blood impedance aggregation in response to collagen, ADP and AA. The PS was derived using principal component analysis from healthy controls off antiplatelet therapy. A cohort of 124 subjects with CVD on aspirin was evaluated as a comparator group. Results: A PS was constructed using 12 measurements from LTA and whole blood aggregation, which accounted for 75% of the variation. The PS significantly correlated with all the platelet measurements used to construct the score (P<0.001 for each measurement). During weeks 1 to 3, the weekly correlation and reproducibility were excellent (r>0.77, ICC 0.82, P<.0001). After 1-week of aspirin therapy, the post-PS score shifted to lower values (P<0.001) and significantly correlated with the pre-PS score (r=0.64, p<.001). Among controls, female sex was the only variable associated with higher PS after multivariable adjustment (P=0.01). The PS was significantly higher in subjects with CVD (-123.8 [-151.5, -83.23]) versus healthy controls (-101.4 [-140.3, -62.03]; P=0.04). Conclusion: Platelet activity can be summarized into a PS that is reproducible over time, significantly associated with platelet activity measured on aspirin, and higher in women and subjects with CVD. Future studies are needed to investigate this score in other high-risk phenotypes and to determine its association with incident cardiovascular events.