Reversal of the antiplatelet effect of ticagrelor by simulated platelet transfusion

BACKGROUND: Reversal of antiplatelet therapy is desirable in patients presenting with life-threatening bleeding or requiring urgent surgery. This study aimed to examine ticagrelor reversal using donor platelets and to explore the effects of residual ticagrelor on donor platelets. STUDY DESIGN AND METHODS: In Cohort 1, 16 healthy subjects were treated with ticagrelor 90 mg twice daily alone or in combination with aspirin 100 mg once daily for 7 days followed by single blood sampling for preparation of platelet-rich plasma. An additional 16 healthy subjects served as controls. In Cohort 2, 16 healthy subjects were treated with ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 7 days followed by serial blood samplings for preparation of platelet-poor plasma (PPP). An additional 16 healthy subjects served as controls. RESULTS: In Cohort 1, inhibition of adenosine diphosphate-induced platelet aggregation (PL_ADP ) by ticagrelor could not be fully reversed by mixing with up to 90% control platelets, whereas inhibition of arachidonic acid-induced platelet aggregation by aspirin was fully reversed with the addition of 60% control platelets. In Cohort 2, 10% PPP obtained from ticagrelor-treated subjects reduced PL_ADP from 74% to 40% at 2 hours, 72% to 58% at 6 hours, and 73% to 59% at 10 hours, while 10% or 20% PPP obtained from clopidogrel-treated subjects did not inhibit PL_ADP . CONCLUSION: The antiplatelet effect of ticagrelor cannot be fully reversed by donor platelets, which could be explained by the presence of active drug. The effect of residual drug on donor platelets appears to be evident for at least 10 hours after ticagrelor ingestion.