title: Impact of dabigatran on platelet function and fibrinolysis.
abstract: BACKGROUND
  We sought to evaluate the potential enhanced fibrinolytic and antiplatelet activity of dabigatran etexilate (DE) due to decreased thrombin levels in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation (NVAF).
  
  
  METHODS
  Consecutive patients with cerebrovascular diseases and NVAF that were treated with DE in a tertiary university hospital. Fibrinolysis and platelet function were assessed by thromboelastometry (ROTEM) and platelet function analyzer (PFA)-100, respectively, before and after treatment with DE. Conventional coagulation tests, endogenous thrombin potential (ETP) and hemoclot thrombin inhibitors (HTI), were also performed in order to detect any possible correlation between dabigatran plasma levels, its anticoagulant activity and the intensity of platelet dysfunction or fibrinolysis.
  
  
  RESULTS
  A total of nineteen patients fulfilled our inclusion criteria (mean age 62.3±7.2years; 47% males; median CHADS2-score: 3; interquartile range: 2-4). DE treatment was associated with a significant reduction of the lysis index (LI60) at 60min (p=0.036), and prolongation of the PFA-100 CEPI closure time (p=0.024). After dabigatran treatment, abnormal PFA-100 results were obtained in two patients (11%, 95% CI: 2%-33%). DE levels (determined by HTI) were strongly inversely correlated (rho=-0.85; p<0.001) with the area under the curve (AUC) values in ETP assay. Νo association was found between HTI and PFA-100 CEPI CT (p=0.64), or LI60 measurements (p=0.60).
  
  
  CONCLUSIONS
  Our findings indicate that DE might affect platelet function and fibrinolysis and highlight the potential role of ETP as an alternative option in DE monitoring. The intensity and clinical relevance of DE antiplatelet and fibrinolytic effects require further investigation.
authors.affiliation: Laboratory of Haematology & Blood Bank Unit, "Attikon" University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Argirios E
authors.initials: AE
authors.lastname: Tsantes
authors.affiliation: Laboratory of Haematology & Blood Bank Unit, "Attikon" University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Elias
authors.initials: E
authors.lastname: Kyriakou
authors.affiliation: Department of Pharmacology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Stefanos
authors.initials: S
authors.lastname: Bonovas
authors.affiliation: Second Department of Neurology, "Attikon" University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Chondrogianni
authors.affiliation: Second Department of Neurology, "Attikon" University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Zompola
authors.affiliation: Second Department of Neurology, "Attikon" University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Chrissoula
authors.initials: C
authors.lastname: Liantinioti
authors.affiliation: Second Department of Neurology, "Attikon" University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Athina
authors.initials: A
authors.lastname: Simitsi
authors.affiliation: Second Department of Neurology, "Attikon" University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Aristeidis H
authors.initials: AH
authors.lastname: Katsanos
authors.affiliation: Laboratory of Haematology & Blood Bank Unit, "Attikon" University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Atta
authors.affiliation: Second Cardiology Department, "Attikon" University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Ignatios
authors.initials: I
authors.lastname: Ikonomidis
authors.affiliation: Department of Microbiology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Violetta
authors.initials: V
authors.lastname: Kapsimali
authors.affiliation: Second Department of Critical Care Medicine, "Attikon" University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Petros
authors.initials: P
authors.lastname: Kopterides
authors.affiliation: Second Department of Neurology, "Attikon" University Hospital, School of Medicine, University of Athens, Athens, Greece; International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic. Electronic address: tsivgoulisgiorg@yahoo.gr.
authors.forename: Georgios
authors.initials: G
authors.lastname: Tsivgoulis
mesh_terms: D000368:Aged; D000991:Antithrombins / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000097:blood* / Q000188:drug therapy*; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D000069604:Dabigatran / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013916:Thrombelastography / Q000379:methods
chemical_list: D000991:Antithrombins; D000069604:Dabigatran
keywords: Atrial fibrillation; Dabigatran; Direct thrombin inhibitor; Fibrinolysis; Ischemic stroke; Platelet function