Comparison of Three Tests to Distinguish Platelet Reactivity in Patients with Renal Impairment during Dual Antiplatelet Therapy

Abstract

Background: Clopidogrel and aspirin combination remains a cornerstone for modern dual antiplatelet therapy (DAPT) following coronary stenting. Although monitoring is not currently recommended, certain high-risk cohorts may benefit from tailoring antiplatelet options to reduce thrombotic or/and hemorrhagic risks. Patients with diminished estimated glomerular filtration rate (eGFR) are prone to both vascular occlusions and bleeding events in whom monitoring may be especially advantageous. We compared the residual platelet reactivity assessed by 3 conventional tests during the maintenance antiplatelet therapy dependent on eGFR. Methods: Post-stenting patients (n = 701) receiving aspirin 100 mg/daily and clopidogrel 75 mg/daily were prospectively enrolled in the cross-sectional single-center study. Patients were dichotomized into 5 groups: eGFR >90, 60-89, 30-59, <30 ml/min/1.73 m², and dialysis. Platelet reactivity by VerifyNow™, light transmittance aggregometry (LTA), and Multiplate analyzer by multiple electrode platelet aggregometry (MEA) assays together with eGFR calculations were done simultaneously at 1 month after coronary stenting. Results: VerifyNow assay distinguished residual platelet reactivity dependent on eGFR deterioration (191 ± 72 vs. 216 ± 78 vs. 248 ± 80 vs. 264 ± 70 vs. 317 ± 96 PRU; p < 0.001). In contrast, LTA (34.3 ± 18.1 vs. 34.7 ± 18.1 vs. 38.0 ± 16.6 vs. 33.0 ± 17.3 vs. 34.1 ± 29.3%; p = 0.242), or MEA (37.2 ± 19.6 vs. 33.8 ± 18.4 vs. 38.6 ± 21.4 vs. 36.5 ± 20.5 vs. 38.3 ± 28.3 AU/min; p = 0.086) failed to triage platelet reactivity in renal patients. Agreement among assays to identify patients with impaired platelet reactivity and eGFR during antiplatelet therapy was low. The multivariable regression analyses confirmed the VerifyNow advantage, since the differences in the platelet reactivity were highly significant for all renal impairment (RI) groups. In contrast, LTA did not distinguish RI patients, and for the MEA, only RI5 (dialysis) cohort exhibit borderline significant decline of residual platelet reactivity. Conclusion: Among 3 assays, VerifyNow was capable to reliably triage residual platelet reactivity in post-stenting DAPT patients dependent on the gradual decline of eGFR during therapy with clopidogrel and aspirin. These data should be confirmed in a large validation longitudinal trial, and may justify future platelet activity monitoring for potential regimen/dose adjustment in high-risk patients. The clinical implications of these data are still unclear, but may give an indication as to whether or when DAPT dose adjustment will become a reality.

Clopidogrel-Related High Residual Platelet Reactivity Associated with Estimated Glomerular Filtration Rate in Patients with Acute Ischemic Stroke

“…This outcome may be attributed to the utilization of whole blood samples, which could potentially interact with certain markers in the VerifyNow system [19]. Furthermore, previous studies have shown that the use of different assays to detect platelet reactivity in patients with CKD may cause differences in results [12,20]. Various factors, such as diabetes, smoking, hypertension, congestive heart failure, and elderly age, have been associated with the occurrence of HRPR and the associated decline in renal function [21][22][23].…”

Red Blood Cells as Redox Modulators in Hemolytic Anemia

“…They have an inherent ability to produce ROS by various pathways-as a by-product of the mitochondrial respiratory chain [38] and by the NADH/NADPH oxidase [for a review see [39]] produced mainly in the pentose cycle [40]. ROS, along with NO, adenosine, and prostacyclins, may play a profound role in the regulation of platelet activities [41]. Many studies demonstrated that their functioning during clot formation involves ROS; for example, platelet activators, such as thrombin, increase ROS generation [42][43][44].…”

Platelet thrombus formation in patients with end-stage renal disease before and after hemodialysis as measured by the total thrombus-formation analysis system

“…There are numerous studies assessing bleeding and thrombotic propensities in different patient populations, including those with ESRD, using different platelet function methods. Light transmission aggregometry and other platelet aggregation tests, including Multiplate analyzer and VerifyNOW, which all depend on the addition of soluble platelet agonists, such as collagen, arachidonic acid or ADP to assess platelet reactivity in platelet-rich plasma or whole blood, have been used in various study settings [ 5 , 6 ]. Other methods used are e.g., flow cytometry analysis of platelet glycoprotein receptor expression and functional tests of VWF enabling the evaluation of other platelet function aspects including platelet adhesion [ 7 – 10 ].…”