Comparison of closure time and whole blood impedance aggregometry to light transmission platelet aggregometry for the assessment of platelet response to aspirin and P2Y12 inhibitor therapies: a large-scale study in the outpatient population

Introduction Light transmission platelet aggregometry (LTA) is considered the clinical gold standard for measuring platelet response to aspirin and P2Y12 inhibitor therapies. However, LTA is cumbersome and time-consuming to perform, is not routinely available in all clinical laboratories, and is highly sensitive to pre-analytical variables, making it difficult to perform in all patient populations. Whole blood-based methods are logistically more feasible and commonly available, but there is currently no consensus on whether these methods are more efficacious in measuring anti-platelet therapy response, and if so, which are the most appropriate and under what conditions.

Method Platelet response to aspirin therapy was measured via closure time with collagen and epinephrine (PFA-100 [Siemens]), and response to P2Y12 inhibitors was measured using whole blood impedance aggregometry (WBA, Multiplate [Roche]) in the outpatient population. Both PFA and WBA were compared against the gold standard LTA. The study population included 1,069 patients taking antiplatelet therapy. Patients were stratified by aspirin monotherapy (ASA, n=714), P2Y12 monotherapy (P2Y12, n=59), and aspirin and P2Y12 dual antiplatelet therapy (DAPT, n=230). Low response was denoted by a total platelet aggregation of less than 70%, PFA <161 seconds, WBA with ADP >533 U, and WBA with ADP/prostaglandin E1 (PGE1) >310 U. Statistical analysis was performed using the two-tailed McNemar test. A p-value of <0.05 was considered statistically significant.

Results Age and sex were comparable between groups and average platelet counts across the three groups ranged between 243-257x109/L. In the ASA group, 62.3% were found to have a low platelet response on PFA-100 compared to 70.4% with LTA-epinephrine, 88.7% with LTA-arachidonic acid, and 79.5% with LTA-collagen (p<0.0001 each). In the P2Y12 group, WBA revealed low response in 84.7% (ADP reagent) and 86.4% (ADP/PGE1) of patients as compared to 78.0% when tested with LTA-ADP. These results were not statistically significant, indicating that WBA and LTA have comparable efficacy in measuring the platelet response to P2Y12 therapy. In the DAPT group, PFA-100 was again found to be less sensitive than LTA, revealing a low response in 78.7% of patients as compared to 81.7% (LTA-epinephrine, p>0.05, ns), 97.8% (arachidonic acid p<0.0001), and 97.4% (collagen, p<0.0001). In the same group, WBA with ADP and ADP with PGE1 again revealed comparable if not better detection of low responders (both 87.0%, p<0.0001 each).

Conclusion Our data reveal that PFA-100 is not reliable to assess ASA response, either in monotherapy or DAPT. By contrast, WBA was comparable to LTA in detecting P2Y12 inhibitor response in monotherapy as well as in DAPT. Surprisingly, LTA was not superior to WBA in detecting P2Y12 responders especially in the group of patients on DATP, which might be explained by the overall more compromised platelet function in these patients.

Publication History

Article published online:
20 February 2023