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Reversal strategy in antagonizing the P2Y12-inhibitor ticagrelor
Article first published online: 23 SEP 2013
© 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd
European Journal of Clinical Investigation
Volume 43, Issue 12, pages 1258–1261, December 2013
How to Cite
Eur J Clin Invest 2013; 43 (12): 1258–1261
Registration number: NCT01369186
- Issue published online: 19 NOV 2013
- Article first published online: 23 SEP 2013
- Accepted manuscript online: 29 AUG 2013 09:40AM EST
- Manuscript Accepted: 26 AUG 2013
- Manuscript Received: 28 FEB 2013
- platelet aggregation;
Patients on antiplatelet therapy have a higher incidence of bleeding complications. Reversal of antiplatelet drug effects is an important issue at trauma or emergency departments. For old and conventional anticoagulants, reversal strategies are established. While the effects of ticagrelor are reversible, developing a method to restore platelet function in patients is of importance due to its longer half-life (approximately 8 h), compared with other P2Y12-inhibitors.
Materials and methods
We report an ex vivo model to reverse the effects of the novel and highly effective P2Y12-inhibitor ticagrelor in 20 healthy volunteers. To normalize platelet reactivity, we added increasing amounts of autologous platelet-rich plasma (PRP) to whole blood which was obtained 3 h after the intake of 180 mg of ticagrelor. Platelet aggregation was assessed by whole blood multiple electrode aggregometry (MEA), which is based on impedance aggregometry.
The basal ADP-induced platelet aggregation averaged 71 ± 16 U (Units). Ticagrelor decreased ADP-induced platelet aggregation to 16 ± 8 U. A clear dose-response was obtained after spiking whole blood with increasing amounts of PRP. It is estimated that ≥2 units of apheresis platelet concentrates will be necessary to completely restore baseline platelet aggregation in the majority of patients after ticagrelor.
Platelets dose dependently improve ex vivo platelet aggregation of subjects after a loading dose of 180 mg of ticagrelor, making transfusion of platelet concentrates potentially useful in bleeding patients and those who need to undergo emergency surgery.