title: Point-of-care coagulation testing for assessment of the pharmacodynamic anticoagulant effect of direct oral anticoagulant.
abstract: BACKGROUND
  This investigation was carried out with already available point-of-care testing (POCT) systems for coagulation parameters to evaluate the qualitative and semiquantitative determination of the time- and concentration-dependent anticoagulant effects of the direct oral anticoagulants rivaroxaban and dabigatran.
  
  
  METHODS
  The whole blood prothrombin time (PT), activated partial thromboplastin time (aPTT), and activated clotting time (ACT) were determined using the GEM PCL Plus coagulation system. Whole blood PT was also measured on the CoaguCheck XS instrument. In addition, PT and aPTT values were obtained in citrated plasma using the PT reagent Neoplastin Plus and the STA APTT reagent. Drug concentrations of rivaroxaban and dabigatran were determined with a chromogenic anti-Xa assay and the hemoclot assay, which are reported to have good agreement with liquid chromatography coupled with tandem mass spectrometry measurements. POCT was performed in 27 consecutive patients who received rivaroxaban 10, 15, or 20 mg once daily and in 15 patients receiving dabigatran 110 or 150 mg twice daily. Blood samples were collected predose and 2 hours after observed drug intake at steady state.
  
  
  RESULTS
  Two hours after observed rivaroxaban administration, the whole blood PT measured on the GEM PCL Plus was prolonged by an average of 64.5% in comparison with predose levels. Less differentiation was observed for rivaroxaban when the PT was measured on the CoaguCheck XS instrument or in plasma (prolongation of 24.1% and 36.8%, respectively). After 2 hours observed dabigatran administration, the whole blood aPTT was comparable with plasma values and was prolonged by 23.5% in comparison with trough values. Significant concentration-dependent prolongations of the activated clotting time were observed to different extents for both direct anticoagulants.
  
  
  CONCLUSIONS
  Direct oral anticoagulants display variable ex vivo effects on different POCT-assays. POCT for aPTT is sensitive to increased concentrations of dabigatran, whereas the PT-POCT assessed with test systems such as the GEM PCL Plus may be helpful to measure the pharmacodynamic anticoagulant effects of rivaroxaban in emergency clinical situations.
authors.affiliation: *Division of Vascular Medicine, Department of Internal Medicine, Goethe-University Hospital; †Cardio Health Center, Rossmarkt; ‡Department of Neurology, Goethe-University Hospital; and §Institute of Biostatistics and Mathematical Modelling, Goethe-University Hospital, Frankfurt/Main, Germany.
authors.forename: Helen
authors.initials: H
authors.lastname: Mani
authors.forename: Natalie
authors.initials: N
authors.lastname: Herth
authors.forename: Alexander
authors.initials: A
authors.lastname: Kasper
authors.forename: Thomas
authors.initials: T
authors.lastname: Wendt
authors.forename: Gundolf
authors.initials: G
authors.lastname: Schuettfort
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Weil
authors.forename: Waltraud
authors.initials: W
authors.lastname: Pfeilschifter
authors.forename: Birgit
authors.initials: B
authors.lastname: Linnemann
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.forename: Edelgard
authors.initials: E
authors.lastname: Lindhoff-Last
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000097:blood / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000097:blood / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests / Q000295:instrumentation / Q000379:methods*; D000069604:Dabigatran; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000097:blood / Q000627:therapeutic use*; D010644:Phenprocoumon / Q000097:blood / Q000627:therapeutic use; D019095:Point-of-Care Systems / Q000592:standards*; D000069552:Rivaroxaban; D013876:Thiophenes / Q000097:blood / Q000627:therapeutic use*; D055815:Young Adult; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D009025:Morpholines; D013876:Thiophenes; D015091:beta-Alanine; D000069552:Rivaroxaban; D000069604:Dabigatran; D010644:Phenprocoumon