Interindividual variability in platelet reactivity among individuals with or without antiplatelet therapy: results from a large tertiary care hospital

Antiplatelet therapy is crucial for reducing thrombotic events in patients with atherosclerotic disease, but the response vary widely among individuals. The identification of patients at high (HPR), optimal (OPR) or low platelet reactivity (LPR) is dependent on high interlaboratory variability. We report results of a large dataset of patients to assess the gold standard light transmission aggregometry (LTA). A total of 11,913 patients who sequentially underwent LTA assessment using several stimuli (ADP-2µM, collagen-2 µg/ml, arachidonic acid 0.5 mM, epinephrine 10µM) with a standardized methodology between 2004 and 2022 were screened. After application of inclusion-exclusion criteria, 5,901 patients were included and divided into five groups: healthy-volunteers (HV; N = 534); controls (CTR; N = 1073); aspirin-treated patients (ASA; 75-150 mg/die; N = 3280); clopidogrel-treated patients (CLOP; 75 mg/die; N = 495) and patients treated with dual antiplatelet therapy, ASA plus CLOP (DAPT; N = 519). The mean PA% in response to ADP 2 μm was 72.4 ± 33.3 in the CTR population, 40.6 ± 29.9 in the ASA group, 25.1 ± 35.1 in the CLOP group and 10.2 ± 18.5 in the DAPT group. The mean PA% in response to collagen 2 ug/ml was 90.7 ± 10.5 in the CTR population, 40.8 ± 26.3 in the ASA group, 79.4 ± 21.8 in the CLOP group and 17.9 ± 19.9 in the DAPT group. The percentage of patients at OPR following ADP stimuli was 66%, 25%, and 26%, in the ASA, CLOP, and DAPT group, respectively. The percentage of patients at OPR following collagen stimuli was 56%, 22%, and 41%, in the ASA, CLOP, and DAPT group, respectively. LTA was significantly increased in response to ADP (72.4 ± 33.3vs62.7 ± 37.1; p < 0.001) and AA (90.7 ± 15.6vs87.6 ± 20.5; p < 0.001) in CTR compared to HV. Our findings support the concept that a significant proportion of individuals present a hyper- or hypo-reactive platelet phenotype potentially affecting the safety and efficacy of antiplatelet therapy. The variability in response to antiplatelet therapy was particularly evident in patients undergoing single as opposed to dual antiplatelet therapy regimens. These data support ongoing strategies of guided selection of antiplatelet therapy in patients with cardiovascular disease.