Thromb Haemost 2018; 118(11): 1895-1901
DOI: 10.1055/s-0038-1673381
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

In Vitro Reversal of the Anti-Aggregant Effect of Ticagrelor Using Untreated Platelets

Paul C. Kruger
1  Population Health Research Institute, Hamilton, Ontario, Canada
2  Department of Haematology, Fiona Stanley Hospital, Perth, Western Australia, Australia
,
Jack Hirsh
3  Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Vinai C. Bhagirath
1  Population Health Research Institute, Hamilton, Ontario, Canada
3  Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Ke Xu
4  Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
,
Brian Dale
5  School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia
6  Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada
,
Tim A. C. de Vries
1  Population Health Research Institute, Hamilton, Ontario, Canada
,
Jeffrey S. Ginsberg
3  Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
John W. Eikelboom
1  Population Health Research Institute, Hamilton, Ontario, Canada
3  Department of Medicine, McMaster University, Hamilton, Ontario, Canada
6  Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada
,
Noel C. Chan
1  Population Health Research Institute, Hamilton, Ontario, Canada
3  Department of Medicine, McMaster University, Hamilton, Ontario, Canada
6  Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada
› Author Affiliations
Funding This project was supported by the Hamilton Health Sciences New Investigator Fund.

Clinical Trial Registration Unique identifier: NCT03005704 (URL: https://clinicaltrials.gov/ct2/show/NCT03005704).
Further Information

Publication History

29 March 2018

27 August 2018

Publication Date:
17 October 2018 (eFirst)

Abstract

Background Ticagrelor is an anti-platelet agent that is indicated for prevention of thrombosis after acute coronary syndrome or intra-coronary artery stent implantation, but it increases the risk of bleeding. Platelet transfusion has the potential to treat or prevent bleeding in patients taking ticagrelor, but the optimal quantity of platelets and timing of administration have not been fully defined.

Methods and Results Ten healthy subjects took ticagrelor in combination with acetylsalicylic acid for 5 days, and had blood collected prior to treatment and at 2, 10, 24, 48, 72 and 96 hours after the last doses. The potential of platelet transfusion to prevent or reverse bleeding was evaluated by mixing subject and donor platelet-rich plasma in vitro in nine different proportions, and measuring adenosine diphosphate-mediated aggregation by light transmission aggregometry. Spontaneous offset of the anti-aggregant effect of ticagrelor occurred gradually and was complete at 72 hours after the last dose. The addition of donor platelets enhanced the recovery. The addition of the equivalent of six apheresis platelet units produced a 50% relative reversal at 10 hours, and > 90% reversal at 24 hours.

Conclusion Donor platelets enhance reversal of the anti-aggregant effect of ticagrelor in vitro. Donor platelets given in clinically relevant amounts partially reversed ticagrelor at 10 hours after the last dose, and almost fully reversed ticagrelor at 24 hours. The results inform on the potential to reverse ticagrelor in patients who develop bleeding or require emergency surgery.

Supplementary Material