title: The reversal effect of prothrombin complex concentrate (PCC), activated PCC and recombinant activated factor VII against anticoagulation of Xa inhibitor.
abstract: BACKGROUND
  An increasing number of patients are treated with direct-acting oral anticoagulants (DOACs), but the optimal way to reverse the anticoagulant effect is not known. Specific antidotes are not available and prothrombin complex concentrate (PCC), activated PCC (aPCC) and recombinant factor VIIa (rFVIIa) are variously used as reversal agents in case of a major bleeding. We aimed to determine the most effective haemostatic agent and dose to reverse the effect of rivaroxaban in blood samples from patients taking rivaroxaban for therapeutic reasons.
  
  
  METHODS
  Blood samples from rivaroxaban-treated patients (n =50) were spiked with PCC, aPCC and rFVIIa at concentrations imitating 80%, 100% and 125% of suggested therapeutic doses. The reversal effect was assessed by thromboelastometry in whole blood and a thrombin generation assay (TGA) in platelet-poor plasma. Samples from healthy subjects (n =40) were included as controls.
  
  
  RESULTS
  In thromboelastometry measurements, aPCC and rFVIIa had a superior effect to PCC in reversing the rivaroxaban-induced lenghtening of clotting time (CT). aPCC was the only haemostatic agent that shortened the CT down to below the control level. Compared to healthy controls, patients on rivaroxaban also had a prolonged lag time and decreased peak concentration, velocity index and endogenous thrombin potential (ETP) in platelet-poor plasma. aPCC reversed these parameters more effectively than rFVIIa and PCC. There were no differences in efficacy between 80%, 100% and 125% doses of aPCC.
  
  
  CONCLUSIONS
  aPCC seems to reverse the anticoagulant effect of rivaroxaban more effectively than rFVIIa and PCC by evaluation with thromboelastometry and TGA in vitro.
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Box 4950, Nydalen, N-0424 Oslo, Norway.|Department of Haematology, Oslo University Hospital, Box 4950, Nydalen, N-0424 Oslo, Norway.|Department of Haematology, Akershus University Hospital, N-1478 Lørenskog, Norway.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Box 1171, Blindern, N-0318 Oslo, Norway.
authors.forename: Nina Haagenrud
authors.initials: NH
authors.lastname: Schultz
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Box 4950, Nydalen, N-0424 Oslo, Norway.|Department of Haematology, Akershus University Hospital, N-1478 Lørenskog, Norway.
authors.forename: Hoa Thi Tuyet
authors.initials: HTT
authors.lastname: Tran
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Box 4950, Nydalen, N-0424 Oslo, Norway.
authors.forename: Stine
authors.initials: S
authors.lastname: Bjørnsen
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital, Box 4950, Nydalen, N-0424 Oslo, Norway.
authors.forename: Carola Elisabeth
authors.initials: CE
authors.lastname: Henriksson
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Box 4950, Nydalen, N-0424 Oslo, Norway.|Department of Haematology, Oslo University Hospital, Box 4950, Nydalen, N-0424 Oslo, Norway.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Box 1171, Blindern, N-0318 Oslo, Norway.
authors.forename: Per Morten
authors.initials: PM
authors.lastname: Sandset
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Box 4950, Nydalen, N-0424 Oslo, Norway.|Department of Haematology, Oslo University Hospital, Box 4950, Nydalen, N-0424 Oslo, Norway.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Box 1171, Blindern, N-0318 Oslo, Norway.
authors.forename: Pål Andre
authors.initials: PA
authors.lastname: Holme
keywords: Activated prothrombin complex concentrate; Prothrombin complex concentrate; Recombinant aFVIIa; Reversal; Rivaroxaban