Background: Antiplatelet therapy is the mainstay of thromboprophylaxis in patients with advanced atherosclerosis eligible for surgical intervention/endarterectomy. Up to 40% of patients are reported to have high on-treatment platelet reactivity, which is associated with an increased thrombosis risk and warrants a switch in antiplatelet therapy. However, little is known about intra-individual platelet responses to antiplatelet therapy over time, nor about the optimal timing of residual platelet reactivity measurements.

Aims: To determine the optimal moment for monitoring efficacy of P2Y12 inhibitor use by measuring residual platelet reactivity over time in individual patients undergoing carotid endarterectomy (CEA).

Methods: In a prospective, single-centre, observational study, we measured residual platelet reactivity of 50 vascular patients with the VerifyNow, VASP and an in-house developed flow cytometry-based platelet activation test prior to induction of anesthesia and 1 day, 5 days and >2.5 months postoperatively. Eligible subjects included adult patients scheduled for CEA without indication for post-operative intensive care admission, and treated with P2Y12 inhibitors. Presence of the CYP2C19*2 or CYP2C19*3 loss-of-function alleles or the CYP2C19*17 gain-of-function allele were identified by CYP2C19 genetic testing and associated to the measured efficacy of antiplatelet therapy. Informed consent was obtained and the study was approved by the local medical ethics committee.

Results: CEA resulted in a higher platelet response directly post intervention, despite P2Y12 inhibitor intake. First signs of platelet inhibition were observed 5 days postoperatively. Significant inhibition of platelet function was only observed after long-term use, i.e. >2.5 months post-CEA. Loss-of-function due to CYP2C19*2 or CYP2C19*3 alleles or gain-of-function due to the CYP2C19*17 allele were leading in the response of patients to P2Y12 inhibitor use.

Conclusions: Patients undergoing CEA are not protected when P2Y12 inhibitor treatment is started just days prior to surgery, since antiplatelet therapy based on P2Y12 inhibition is only effectively inhibiting platelet reactivity after treatment for weeks.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/intra-individual-residual-platelet-reactivity-upon-antiplatelet-therapy-in-the-perioperative-period-significantly-differs-over-time-what-is-the-ideal-moment-to-monitor-efficacy-of-antiplatelet-thera/