Adrenaline Improves Platelet Reactivity in Ticagrelor-Treated Healthy Volunteers.
Adenosine Diphosphate
/ metabolism
Adolescent
Adult
Blood Coagulation
/ drug effects
Drug Synergism
Epinephrine
/ administration & dosage
Healthy Volunteers
Humans
Infusions, Intravenous
Male
P-Selectin
/ metabolism
Platelet Aggregation
/ drug effects
Platelet Aggregation Inhibitors
/ administration & dosage
Ticagrelor
/ administration & dosage
Young Adult
Journal
Thrombosis and haemostasis
ISSN: 2567-689X
Titre abrégé: Thromb Haemost
Pays: Germany
ID NLM: 7608063
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
pubmed:
20
2
2019
medline:
10
1
2020
entrez:
20
2
2019
Statut:
ppublish
Résumé
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 ( 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.
Sections du résumé
BACKGROUND
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
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.
RESULTS
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 (
CONCLUSION
CONCLUSIONS
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.
TRIAL REGISTRY NUMBER
UNASSIGNED
ClinicalTrials.gov NCT03441412.
Identifiants
pubmed: 30780166
doi: 10.1055/s-0039-1683461
doi:
Substances chimiques
P-Selectin
0
Platelet Aggregation Inhibitors
0
Adenosine Diphosphate
61D2G4IYVH
Ticagrelor
GLH0314RVC
Epinephrine
YKH834O4BH
Banques de données
ClinicalTrials.gov
['NCT03441412']
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
735-743Informations de copyright
Georg Thieme Verlag KG Stuttgart · New York.
Déclaration de conflit d'intérêts
None declared.