title: Measurement and reversal of prophylactic and therapeutic peak levels of rivaroxaban: an in vitro study.
abstract: BACKGROUND
  Rivaroxaban (Xarelto, Bayer HealthCare, Leverkusen, Germany) is a new oral anticoagulant drug. Anticoagulants may cause bleeding, thereby requiring reliable monitoring and efficient therapy. We investigated thromboelastometry versus routine coagulation tests to measure prophylactic and therapeutic concentrations of rivaroxaban and their reversal with prothrombin complex concentrate (PCC) and activated recombinant factor VII (rFVIIa) in vitro.
  
  
  METHODS
  Rivaroxaban was solubilized, and PCC and rFVIIa were added in 2 concentrations to the rivaroxaban-spiked blood samples, and thromboelastometry and measurements were performed.
  
  
  RESULTS
  Rivaroxaban increased tissue factor-activated clotting time (CT(ExTEM)) dose dependently. Activated partial prothrombin time (aPTT), prothrombin time ratio (PTR), and prothrombin time (PT) were changed significantly in both concentrations. Reversal with PCC in both dosages caused no significant change in the measured parameters. For prophylactic rivaroxaban dosage, rFVIIa changed the PT significantly but not CT(ExTEM), aPTT, and PTR. For therapeutic rivaroxaban dosage, the CT(ExTEM) was significantly reduced. The other parameters remained unaffected.
  
  
  CONCLUSIONS
  Thromboelastometry can detect rivaroxaban effects. In vitro rFVIIa seems highly effective for reversal in contrast to PCC.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany mareike.koerber@charite.de.
authors.forename: Mareike Kristina
authors.initials: MK
authors.lastname: Körber
authors.affiliation: Labor Berlin-Charite Vivantes, GmbH, Berlin, Germany Institute for Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Langer
authors.affiliation: Institute for Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ziemer
authors.affiliation: Bayer Healthcare AG, Wuppertal, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Perzborn
authors.affiliation: Institute of Medical Biometrics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Gericke
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
authors.forename: Christian von
authors.initials: Cv
authors.lastname: Heymann
mesh_terms: D000328:Adult; D001779:Blood Coagulation Factors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015942:Factor VIIa / Q000378:metabolism*; D065427:Factor Xa Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D009025:Morpholines / Q000493:pharmacokinetics* / Q000494:pharmacology; D000069552:Rivaroxaban; D013876:Thiophenes / Q000493:pharmacokinetics* / Q000494:pharmacology; D013916:Thrombelastography
chemical_list: D001779:Blood Coagulation Factors; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; C025667:prothrombin complex concentrates; D000069552:Rivaroxaban; D015942:Factor VIIa
keywords: anticoagulants; bleeding; factor Xa inhibitors; rFVIIa