Prevalence of Aspirin Non-Response in Out-Patients and In-Patients as Determined by Multiple Electrode Aggregometry.
Authors: Calatzis Andreas , von Pape Klaus-Werner , Reininger Armin J. , Theisen Franz , Spannagl Michael 
Published: April 2020

Abstract
A control of aspirin response is one proposed strategy for an improvement of anti-platelet therapy. Different methods have been proposed for this indication. We evaluated the prevalence of aspirin non-responsiveness in two different cohorts using a new monitoring method.
Methods: Platelet function was determined using multiple electrode aggregometry (MEA) on the Multiplate analyzer (Dynabyte, Munich, Germany). This device uses a single use test cell with two separate impedance sensors, consisting of a total of 4 electrodes and has 5 channels for parallel tests. Aggregation was triggered using arachidonic acid (0.16 mM, ASPItest, Dynabyte). For the analysis 300 μl of blood are analyzed with the addition of 300 μ saline. Aggregation was quantified by the area under the curve in arbitrary U (1 U corresponds to 10 AU*min). Following IRB approval venous blood was collected from 120 blood donors without anamnestic intake of Aspirin in the 2 weeks before the analysis, in 76 outpatients taking aspirin 25–300 mg/d (mean 128 mg/d) and 341 cardiovascular in-patients on Aspirin 100 mg qd using the direct thrombin inhibitor Melagatran in a final concentration of 15 μ as the anticoagulant.
Results: The distribution of the aggregation values is shown in Fig. 1. The median (min–ax) was 100 (5–159) for the blood donors, 13 (2–71) for the out-patients and 11 (0–145) for the in-patients. When a cut-off of 48 (lower end of a 95% confidence interval for the MEA results of the blood donors) is selected, then 51 of 341 in-patients (15%) would have been stratified as non-responders to the aspirin treatment and 2 of 76 out-patients (2,6%).
Discussion: The comparison of the results of aspirin-treated patients and healthy controls (blood donors) reveals a high sensitivity of the new method for the effect of aspirin. Due to the use of a direct thrombin inhibitor as the anticoagulant in our study platelet function was determined under physiological levels of ionized calcium. The results of the two aspirin-treated cohorts examined shows a similar distribution of aggregation values with an aggregation of less than 30 U in 96% of the out-patients and 80% of the in-patients. Using the cut-off of 48 U (based on the results of the blood donors) more patients would have been stratified as aspirin-resistant in the in-patients compared to the out-patients. The out-patients were members of a cardiovascular sports group and knew long in advance that their platelet function would be analyzed on the particular day. Therefore a high level of compliance in respect to the aspirin intake during the days preceeding the analysis can be expected. In addition the out-patient group was significantly healthier compared to the in-patients.
In conclusion multiple electrode aggregometry showed a high sensitivity for aspirin. The rate of non-response to the treatment seems to be influenced by compliance and comorbidities. Prospective trials are required to prove that aspirin-non-response in this particular method is associated with an increased occurrence of arterial thromboembolism.
Fig. 1 Fig. 1.