PB0366 - Ticagrelor Overdose Managed without Adverse Outcomes: Is Reversal Agent Necessary?

Background: Ticagrelor is an oral, direct-acting, reversible P2Y12 receptor antagonist inhibiting ADP-induced platelet aggregation, and used in combination with low-dose aspirin. Overdose has been reported to cause serious bleeding even fatal. The literature related to toxicity management is very limited. A reversal agent is currently in clinical trial.

Aims: To show that ticagrelor overdose is not necessarily associated with clinical bleeding and hence a reversal agent need not be given prophylactically.

Methods: We describe a case of ticagrelor overdose in which no reversal agent was given and bleeding did not occur. The platelet reactivity was monitored daily with the VerifyNow P2Y12 assay.

Results: A 74 yr old male with history of coronary artery disease and recurrent venous thromboembolism on warfarin presented after intentional intake of a massive dose of ticagrelor 5400 mg (60 tablets of 90 mg). The patient reported diffuse headache and abdominal pain upon arrival at the emergency department. His vital signs and physical examination were unremarkable. The INR was 2.5. Activated charcoal was administered in an effort to prevent gastrointestinal absorption and the patient was monitored with continuous cardiac telemetry. His toxicological analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed a high plasma ticagrelor concentration of 3500 ng/mL and VerifyNow P2Y12 assay was 9 PRU. The platelet reactivity assay showed gradual improvement (Figure). The patient remained clinically stable without bleeding or cardiac arrhythmia despite the high INR. The hemoglobin and platelet count were normal throughout the hospitalization period (Table). He was then discharged uneventfully on day 9 to an inpatient psychiatry unit for rehabilitation.

Conclusion(s): The uneventful recovery from a ticagrelor overdose in this patient suggests that a reversal agent need not be used in the absence of clinically significant bleeding.