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Adrenaline Improves Platelet Reactivity in Ticagrelor-Treated Healthy Volunteers
Univ Gothenburg, Sweden.
Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
Univ Gothenburg, Sweden.
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2019 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 119, no 5, p. 735-743Article in journal (Refereed) Published
Abstract [en]

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. 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 mu g/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. Results Infusion of adrenaline increased ADP-induced aggregation at all doses above 0.01 mu g/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 mu g/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). 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.

Place, publisher, year, edition, pages
GEORG THIEME VERLAG KG , 2019. Vol. 119, no 5, p. 735-743
Keywords [en]
adrenaline; ticagrelor; platelet function; flow cytometry; impedance aggregometry
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:liu:diva-157537DOI: 10.1055/s-0039-1683461ISI: 000467408100008PubMedID: 30780166OAI: oai:DiVA.org:liu-157537DiVA, id: diva2:1328680
Note

Funding Agencies|Swedish Heart and Lung Foundation [20150587]; Vastra Gotaland Region [ALFGBG-725131]

Available from: 2019-06-22 Created: 2019-06-22 Last updated: 2019-11-04

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The full text will be freely available from 2020-01-04 09:44
Available from 2020-01-04 09:44

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Division of Clinical ChemistryFaculty of Medicine and Health SciencesDepartment of Clinical Chemistry
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