A Achilles1, A Mohring1, L Dannenberg1, M Grandoch2, T Hohlfeld2, J W Fischer2, B Levkau3, M Kelm1, T Zeus1, A Polzin1. 1. Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich Heine University Medical Center Dusseldorf, Dusseldorf, Germany. 2. Institute for Pharmacology and Clinical Pharmacology, Heinrich Heine University, Dusseldorf, Germany. 3. Institute of Pathophysiology, West German Heart and Vascular Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Abstract
Essentials Whether or not dabigatran enhances the risk of myocardial infarction is under discussion. We measured platelet reactivity and thrombin receptor expression in dabigatran patients. Platelet reactivity and thrombin receptor expression is enhanced during dabigatran treatment. This should be considered when choosing the optimal direct oral anticoagulant for individuals. SUMMARY: Background The direct oral anticoagulant (DOAC) dabigatran is a direct thrombin inhibitor. Its landmark trial, the RE-LY study, observed a trend towards a higher incidence of myocardial infarctions (MIs) in dabigatran-treated patients. Since then, there have been discussions on whether dabigatran increases the risk of MI. Objective In this study, we aimed to assess platelet reactivity and platelet thrombin receptor expression in dabigatran-treated patients. Methods We conducted a cross-sectional study in 13 hospitalized patients with planned initiation of dabigatran medication. Platelet reactivity was measured by light-transmission aggregometry and platelet thrombin receptor expression was measured by flow cytometry analysis. Results Platelet reactivity was higher after initiation of dabigatran medication as compared with baseline (baseline 44 ± 24% vs. dabigatran 70 ± 25%). Accordingly, the density of both platelet thrombin receptors (protease activated receptor [PAR]-1 and PAR-4) on platelets increased during dabigatran treatment (PAR1, baseline 63 ± 11% vs. dabigatran 70 ± 10%; PAR4, baseline 1.1 ± 0.5% vs. dabigatran 1.6 ± 0.9%). Conclusions Dabigatran increases platelet reactivity by enhancing the thrombin receptor density on platelets. This finding should be considered while choosing the optimal DOAC in individualized medicine.
Essentials Whether or not dabigatran enhances the risk of myocardial infarction is under discussion. We measured platelet reactivity and thrombin receptor expression in dabigatranpatients. Platelet reactivity and thrombin receptor expression is enhanced during dabigatran treatment. This should be considered when choosing the optimal direct oral anticoagulant for individuals. SUMMARY: Background The direct oral anticoagulant (DOAC) dabigatran is a direct thrombin inhibitor. Its landmark trial, the RE-LY study, observed a trend towards a higher incidence of myocardial infarctions (MIs) in dabigatran-treated patients. Since then, there have been discussions on whether dabigatran increases the risk of MI. Objective In this study, we aimed to assess platelet reactivity and platelet thrombin receptor expression in dabigatran-treated patients. Methods We conducted a cross-sectional study in 13 hospitalized patients with planned initiation of dabigatran medication. Platelet reactivity was measured by light-transmission aggregometry and platelet thrombin receptor expression was measured by flow cytometry analysis. Results Platelet reactivity was higher after initiation of dabigatran medication as compared with baseline (baseline 44 ± 24% vs. dabigatran 70 ± 25%). Accordingly, the density of both platelet thrombin receptors (protease activated receptor [PAR]-1 and PAR-4) on platelets increased during dabigatran treatment (PAR1, baseline 63 ± 11% vs. dabigatran 70 ± 10%; PAR4, baseline 1.1 ± 0.5% vs. dabigatran 1.6 ± 0.9%). Conclusions Dabigatran increases platelet reactivity by enhancing the thrombin receptor density on platelets. This finding should be considered while choosing the optimal DOAC in individualized medicine.
Authors: Sophie C Dólleman; Stijn M Agten; Henri M H Spronk; Tilman M Hackeng; Mettine H A Bos; Henri H Versteeg; Anton Jan van Zonneveld; Hetty C de Boer Journal: J Thromb Haemost Date: 2022-02-02 Impact factor: 16.036
Authors: Flávia B B Arantes; Fernando R Menezes; Andre Franci; Carlos J D G Barbosa; Talia F Dalçoquio; Carlos A K Nakashima; Luciano M Baracioli; Remo H M Furtado; Quintiliano S S Nomelini; José A F Ramires; Roberto Kalil Filho; José C Nicolau Journal: Adv Ther Date: 2019-11-22 Impact factor: 3.845
Authors: Rayyan Hemetsberger; Serdar Farhan; Dominika Lukovic; Katrin Zlabinger; Judit Hajagos-Toth; Judit Bota; Hector M Garcia-Garcia; Cihan Ay; Eslam Samaha; Robert Gaspar; Rita Garamvölgyi; Kurt Huber; Mariann Gyöngyösi; Andreas Spannbauer Journal: Front Cardiovasc Med Date: 2021-07-02