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Adrenaline Improves Platelet Reactivity in Ticagrelor-Treated Healthy Volunteers.

Authors :
Singh S
Damén T
Nygren A
Shams Hakimi C
Ramström S
Dellborg M
Lindahl TL
Hesse C
Jeppsson A
Source :
Thrombosis and haemostasis [Thromb Haemost] 2019 May; Vol. 119 (5), pp. 735-743. Date of Electronic Publication: 2019 Feb 19.
Publication Year :
2019

Abstract

Background:  Administration of agents that enhance platelet reactivity may reduce the perioperative bleeding risk in patients treated with the adenosine diphosphate (ADP)-receptor antagonist ticagrelor. Adrenaline potentiates ADP-induced aggregation and activation in blood samples from ticagrelor-treated patients, but it has not previously been evaluated in vivo.<br />Methods:  Ten healthy male subjects were included in an interventional study. A loading dose of ticagrelor (180 mg) was administered, followed 2 hours later by a gradually increased intravenous adrenaline infusion (0.01, 0.05, 0.10 and 0.15 µg/kg/min; 15 minutes at each step). Blood pressure, heart rate, platelet aggregation (impedance aggregometry), platelet activation (flow cytometry), clot formation (rotational thromboelastometry) and adrenaline plasma concentration were determined before and after ticagrelor administration and at the end of each adrenaline step.<br />Results:  Infusion of adrenaline increased ADP-induced aggregation at all doses above 0.01 µg/kg/min. The aggregation increased from median 17 (25-75th percentiles: 14-31) to 25 (21-34) aggregation units ( p  = 0.012) at 0.10 µg/kg/min. Adrenaline infusion also increased ADP-induced fibrinogen receptor activation (from 29 [22-35] to 46 [38-57%]) and P-selectin expression (from 3.7 [3.0-4.3] to 7.7 [4.7-8.6%]), both p  = 0.012. Adrenaline infusion reduced clot formation time (97 [89-110] to 83 [76-90] seconds, p  = 0.008) and increased maximum clot firmness (59 [57-60] to 62 [61-64] mm, p  = 0.007).<br />Conclusion:  Infusion of adrenaline at clinically relevant doses improves in vivo platelet reactivity and clot formation in ticagrelor-treated subjects. Adrenaline could thus potentially be used to prevent perioperative bleeding complications in ticagrelor-treated patients. Studies in patients are necessary to determine the clinical importance of our observations.<br />Trial Registry Number:  ClinicalTrials.gov NCT03441412.<br />Competing Interests: None declared.<br /> (Georg Thieme Verlag KG Stuttgart · New York.)

Details

Language :
English
ISSN :
2567-689X
Volume :
119
Issue :
5
Database :
MEDLINE
Journal :
Thrombosis and haemostasis
Publication Type :
Academic Journal
Accession number :
30780166
Full Text :
https://doi.org/10.1055/s-0039-1683461