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Adrenaline Improves Platelet Reactivity in Ticagrelor-Treated Healthy Volunteers.

Journal article
Authors Sukhi Singh
Tor Damén
Andreas Nygren
Caroline Andersson Shams Hakimi
Sofia Ramström
Mikael Dellborg
Tomas L Lindahl
Camilla Hesse
Anders Jeppsson
Published in Thrombosis and haemostasis
Volume 119
Issue 5
Pages 735-743
ISSN 2567-689X
Publication year 2019
Published at Institute of Clinical Sciences, Department of Anesthesiology and Intensive care
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 735-743
Language en
Links dx.doi.org/10.1055/s-0039-1683461
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Clinical Medicine

Abstract

 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. 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. 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). 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. ClinicalTrials.gov NCT03441412.

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