title: Impact of rivaroxaban compared with warfarin on the coagulation status in Japanese patients with non-valvular atrial fibrillation: a preliminary analysis of the prothrombin fragment 1+2 levels.
abstract: BACKGROUND
  Rivaroxaban is an oral anticoagulant that effectively prevents thromboembolic complications using fixed doses without requiring laboratory monitoring. In this study, we aimed to examine the coagulation status in patients with non-valvular atrial fibrillation (NVAF) treated with rivaroxaban compared with warfarin.
  
  
  RESULTS
  The study group consisted of 85 consecutive Japanese patients with NVAF who received rivaroxaban (n=33) or warfarin (n=52) from June 2013 to February 2014. We compared the coagulation status between the rivaroxaban and warfarin treatments. The prothrombin time (PT) values did not significantly differ between the two groups. However, the prothrombin fragment 1+2 (F1+2) level, a marker of thrombin generation, was significantly higher in the rivaroxaban group than the warfarin group (202±88pmol/l vs. 114±79pmol/l, p<0.001). Next, we collected blood samples from 18 patients taking rivaroxaban at 3h and 15h after the drug intake and evaluated the time-dependent changes in the coagulation status. The PT values at 3h after the drug intake were significantly more prolonged than those at 15h (p<0.001). However, there were no significant differences in the F1+2 levels between the two time points (194±73pmol/l [at 3h] vs. 165±61pmol/l [at 15h], p=0.112).
  
  
  CONCLUSIONS
  Our preliminary results suggest that the thrombin generation level is stable regardless of the time elapsed after rivaroxaban intake, and warfarin treatment may inhibit thrombin generation more aggressively than rivaroxaban.
authors.affiliation: Cardiovascular Division, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Sumiyoshi Clinic Hospital, Mito, Ibaraki, Japan. Electronic address: ktajiri@md.tsukuba.ac.jp.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Tajiri
authors.affiliation: Cardiovascular Division, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.affiliation: Cardiovascular Division, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Sumiyoshi Clinic Hospital, Mito, Ibaraki, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Harunari
authors.affiliation: Cardiovascular Division, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Sumiyoshi Clinic Hospital, Mito, Ibaraki, Japan.
authors.forename: Nobutake
authors.initials: N
authors.lastname: Shimojo
authors.affiliation: Sumiyoshi Clinic Hospital, Mito, Ibaraki, Japan; Ibaraki Health Service Association Institute, Mito, Ibaraki, Japan.
authors.forename: Iwao
authors.initials: I
authors.lastname: Yamaguchi
authors.affiliation: Cardiovascular Division, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Aonuma
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology*; D044466:Asian People; D001281:Atrial Fibrillation / Q000097:blood*; D065427:Factor Xa Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000187:drug effects*; D011516:Prothrombin / Q000187:drug effects*; D011517:Prothrombin Time; D000069552:Rivaroxaban / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism*; D013997:Time Factors; D014859:Warfarin / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D014859:Warfarin; D011516:Prothrombin; D000069552:Rivaroxaban; D013917:Thrombin
keywords: Anticoagulants; Atrial fibrillation; Coagulation; Rivaroxaban; Warfarin