title: In vitro reversal of supratherapeutic rivaroxaban levels with coagulation factor concentrates.
abstract: A bleeding patient undergoing therapy with new oral anticoagulants is every clinician's nightmare as no specific reversal agent is available yet. This in vitro study investigated the effect of prothrombin complex concentrate (PCC), recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (aPCC) on supratherapeutic rivaroxaban concentrations using standard laboratory parameters (prothrombin time [PT], activated partial thromboplastin time [aPTT] and PT ratio) and thromboelastometry (clotting time [CT]).
  
  
  
  Blood samples from 10 healthy volunteers were collected and spiked with a supratherapeutic dose of rivaroxaban. Afterwards PCC, rFVIIa and aPCC were added in two doses. The laboratory parameters were measured and thromboelastometry was performed.
  
  
  
  The addition of the reversal agents had the following statistically significant effects (all p<0.01): +25 IU/kg PCC: CT -15 s, aPTT +5 s; +50 IU/kg PCC: aPTT +11 s; +90 μg rFVIIa: CT -141 s; +25 IU/kg aPCC: CT -142 s, aPTT -9 s, PT ratio +14%, PT -10.5 s; +50 IU/kg aPCC: CT -118 s, aPTT -7 s, PT ratio +17%, PT -12.2 s.
  
  
  
  rFVIIa and aPCC, but not PCC, appear to shorten coagulation times significantly in standard laboratory and thromboelastometry assays. These results need confirmation through evaluation of these agents in the clinical setting.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin Germany.
authors.forename: Mareike K
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 Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Langer
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Kaufner
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Universitätsklinikum Giessen-Marburg Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Sander
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin Germany.|Department of Anaesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Therapy, "Vivantes Netzwerk für Gesundheit GmbH Klinikum im Friedrichshain", Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Von Heymann
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D015942:Factor VIIa / Q000494:pharmacology; D006801:Humans; D011517:Prothrombin Time; D000069552:Rivaroxaban; D013916:Thrombelastography
chemical_list: D001779:Blood Coagulation Factors; D000069552:Rivaroxaban; D015942:Factor VIIa