title: Dabigatran enhances platelet reactivity and platelet thrombin receptor expression in patients with atrial fibrillation.
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.
  
  
  
  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.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich Heine University Medical Center Dusseldorf, Dusseldorf, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Achilles
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich Heine University Medical Center Dusseldorf, Dusseldorf, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Mohring
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich Heine University Medical Center Dusseldorf, Dusseldorf, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Dannenberg
authors.affiliation: Institute for Pharmacology and Clinical Pharmacology, Heinrich Heine University, Dusseldorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Grandoch
authors.affiliation: Institute for Pharmacology and Clinical Pharmacology, Heinrich Heine University, Dusseldorf, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Hohlfeld
authors.affiliation: Institute for Pharmacology and Clinical Pharmacology, Heinrich Heine University, Dusseldorf, Germany.
authors.forename: J W
authors.initials: JW
authors.lastname: Fischer
authors.affiliation: Institute of Pathophysiology, West German Heart and Vascular Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Levkau
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich Heine University Medical Center Dusseldorf, Dusseldorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kelm
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich Heine University Medical Center Dusseldorf, Dusseldorf, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Zeus
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich Heine University Medical Center Dusseldorf, Dusseldorf, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Polzin
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage; D016718:Arachidonic Acid / Q000737:chemistry; D001281:Atrial Fibrillation / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000737:chemistry; D003430:Cross-Sectional Studies; D000069604:Dabigatran / Q000008:administration & dosage*; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy; D010865:Pilot Projects; D010974:Platelet Aggregation; D018179:Receptors, Thrombin / Q000378:metabolism*; D012044:Regression Analysis; D012307:Risk Factors; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D018179:Receptors, Thrombin; D016718:Arachidonic Acid; D003094:Collagen; D013917:Thrombin; D000069604:Dabigatran
keywords: dabigatran; myocardial infarction; platelet; protease activated receptors; thrombin