title: Rivaroxaban and warfarin achieve effective anticoagulation, as assessed by inhibition of TG and in-vivo markers of coagulation activation, in patients with venous thromboembolism.
abstract: BACKGROUND
  Rivaroxaban is non-inferior to warfarin for the treatment of venous thromboembolism, with regard to clinical efficacy and safety. The ex-vivo effects of warfarin versus therapeutic dose rivaroxaban on in-vivo markers of coagulation activation and thrombin generation remain undefined. The aim of this study was to compare the effects of warfarin and therapeutic dose rivaroxaban on ex-vivo thrombin generation (TG), and the in-vivo markers of coagulation activation, prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT), and D-dimer.
  
  
  METHODS
  Eighty-five patients with venous thromboembolism were studied, 45 on warfarin, target INR 2.5 and 40 on rivaroxaban 20mg once daily.
  
  
  RESULTS
  Anticoagulation was in therapeutic range in 71% (32/45) warfarin and 65% (26/40) rivaroxaban treated patients. 8 patients on warfarin and 9 patients on rivaroxaban had subtherapeutic INR and rivaroxaban levels respectively. Both rivaroxaban and warfarin reduced endogenous thrombin potential (ETP) and peak thrombin, and prolonged lag time and time to peak, compared to normal controls (p<0.0001). The lag time and time to peak TG were longer, and peak thrombin was lower in patients receiving rivaroxaban (p<0.0001) compared with warfarin, although warfarin-treated patients had lower ETP (p=0.0008). In-vivo coagulation activation markers were within the normal ranges in all rivaroxaban-treated patients (including those with levels considered to be subtherapeutic) and in 37/45 warfarin-treated patients who had an INR≥2.0. The warfarin-treated patients with subtherapeutic INRs exhibited slightly raised F1.2 and/or TAT.
  
  
  CONCLUSIONS
  In conclusion, both rivaroxaban and warfarin provided effective anticoagulation, as assessed by inhibition of TG and makers of in-vivo coagulation activation.
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, London, UK. Electronic address: deeparanjani@hotmail.com.
authors.forename: D R J
authors.initials: DR
authors.lastname: Arachchillage
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Efthymiou
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, London, UK.
authors.forename: I J
authors.initials: IJ
authors.lastname: Mackie
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, London, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: Lawrie
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, London, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Machin
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, London, UK; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Cohen
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D000069552:Rivaroxaban; D013876:Thiophenes / Q000627:therapeutic use*; D054556:Venous Thromboembolism / Q000188:drug therapy*; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D014859:Warfarin; D000069552:Rivaroxaban
keywords: D-dimer; Rivaroxaban; Warfarin; prothrombin fragment 1.2; thrombin generation; thrombin-antithrombin complex