title: Measuring the activity of apixaban and rivaroxaban with rotational thrombelastometry.
abstract: BACKGROUND
  Routine drug monitoring is not required for the two novel direct factor Xa inhibitors apixaban and rivaroxaban. Rapidly available test results might be beneficial in case of bleeding or prior to urgent surgery.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the applicability of the two rotational thrombelastometry (ROTEM®) -modifications Low-tissue factor activated ROTEM® (LowTF-ROTEM®) and Prothrombinase induced clotting time - activated ROTEM® (PiCT®-ROTEM®) for determination of apixaban and rivaroxaban in vitro and ex vivo.
  
  
  METHODS
  Blood samples from 20 volunteers were spiked with apixaban / rivaroxaban to yield samples with ascending drug concentrations ranging from 50 - 400ng/mL. LowTF - and PiCT® modified ROTEM® tests and determination of the corresponding antifactor Xa activity were performed in duplicate in 280 samples. LowTF-ROTEM® tests were performed in samples from 20 patients on apixaban or rivaroxaban therapy and 20 controls.
  
  
  RESULTS
  There was a strong correlation between apixaban / rivaroxaban plasma concentrations and the LowTF-ROTEM® parameters Clotting time (CT; spearman correlation coefficient (SCC) 0.81 and 0.81, respectively) and Time to maximum velocity (t,MaxVel; SCC: 0.81 and 0.80, resp.) and a low to moderate correlation for the PiCT®-ROTEM® parameters CT (SCC: 0.38 and 0.59, resp.) and t,MaxVel. (0.51 and 0.69, resp.) in the in vitro experiments. LowTF-ROTEM CT was significantly prolonged in patients on apxiaban or rivaroxaban therapy compared to controls.
  
  
  CONCLUSIONS
  LowTF-ROTEM® could be a valuable diagnostic tool for rapid determination of the effect of apixaban and rivaroxaban at the point of care.
authors.affiliation: Department of Anaesthesia, General Intensive Care and Pain Control, Medical University of Vienna, Vienna, Austria.
authors.forename: Dieter
authors.initials: D
authors.lastname: Adelmann
authors.affiliation: Department of Anaesthesia, General Intensive Care and Pain Control, Medical University of Vienna, Vienna, Austria.
authors.forename: Marion
authors.initials: M
authors.lastname: Wiegele
authors.affiliation: Department of Anaesthesia, General Intensive Care and Pain Control, Medical University of Vienna, Vienna, Austria.
authors.forename: Rudolf Karl
authors.initials: RK
authors.lastname: Wohlgemuth
authors.affiliation: Department of Anaesthesia, General Intensive Care and Pain Control, Medical University of Vienna, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Koch
authors.affiliation: Section for Medical Statistics, Medical University of Vienna, Vienna, Austria.
authors.forename: Sophie
authors.initials: S
authors.lastname: Frantal
authors.affiliation: Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Quehenberger
authors.affiliation: Department of Anaesthesia, General Intensive Care and Pain Control, Medical University of Vienna, Vienna, Austria.
authors.forename: Gisela
authors.initials: G
authors.lastname: Scharbert
authors.affiliation: Department of Anaesthetics and Intensive Care, Evangelical Hospital Vienna, Vienna, Austria.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Kozek-Langenecker
authors.affiliation: Department of Anaesthesia, General Intensive Care and Pain Control, Medical University of Vienna, Vienna, Austria. Electronic address: eva.schaden@meduniwien.ac.at.
authors.forename: Eva
authors.initials: E
authors.lastname: Schaden
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects*; D065427:Factor Xa Inhibitors / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009025:Morpholines / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D019095:Point-of-Care Systems; D011720:Pyrazoles / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D011728:Pyridones / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D000069552:Rivaroxaban; D013876:Thiophenes / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D013916:Thrombelastography / Q000379:methods*
chemical_list: D065427:Factor Xa Inhibitors; D009025:Morpholines; D011720:Pyrazoles; D011728:Pyridones; D013876:Thiophenes; C522181:apixaban; D000069552:Rivaroxaban
keywords: Apixaban; Blood coagulation tests; Point-of-Care coagulation tests; Rivaroxaban; Thrombelastography