• Théo Willeman, Raphael Marlu, Holger Böhle, Gilles Francony, Jean-François Jourdil, Xavier Fonrose, and Françoise Stanke-Labesque.
• a Laboratory of Pharmacology, Toxicology and Pharmacogenetics , Grenoble-Alpes University Hospital , Grenoble , France.
• Clin Toxicol (Phila). 2018 Dec 1; 56 (12): 1200-1203.

BackgroundTicagrelor is a direct and reversible competitive antagonist of the P2Y12 receptor and inhibits platelet activation. Although adverse bleeding is common, fatal intoxication has never been documented.Case DescriptionA 47-year-old man died from a severe cerebral hemorrhage secondary to a fall and cranial trauma 4 d after the massive intake of ticagrelor. Iterative platelet transfusions did not improve his condition. Toxicological analyses by liquid chromatography tandem mass spectrometry (LC-MS/MS) revealed high plasma concentrations of ticagrelor (3343 µg/L) and its active metabolite AR-C124910XX (656 µg/L) 10 h after intake. The approximate ingested dose was extrapolated to 1677 mg. Assessment of ADP-induced platelet aggregation and platelet Vasodilator Stimulated Phosphoprotein phosphorylation (VASP), 2 and 3 d after admission, respectively, showed the persistence of platelet inhibition.DiscussionTo the best of our knowledge, no prior fatal cases have been reported and documented with both ticagrelor and AR-C124910XX concentrations. Our findings highlight the need for a specific antidote to manage such complications resulting from ticagrelor overdose.

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