Prothrombin complex concentrate reverses the anticoagulant effect of rivaroxaban in healthy volunteers

Elise S. Eerenberg, Meertien K. Sijpkens, Pieter W. Kamphuisen, Joost C.M. Meijers, Marcel Levi

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Rivaroxaban is a novel oral antithrombotic agent in the class of specific factor Xa inhibitors, and is licensed in Europe and Canada for the prevention of venous thromboembolism after elective orthopedic surgery. Despite its stable pharmacokinetic and pharmacodynamic profile, immediate reversal may be required in case of a major bleeding or emergency surgery. No specific antidote is currently available, although Prothrombin Complex Concentrate (PCC) seems effective in animal studies. This study is the first to investigate the ability of PCC to reverse the antithrombotic effect of Rivaroxaban in humans. Methods: In a randomized, double-blind, placebo-controlled trial, twelve healthy male subjects received Rivaroxaban 20mg twice daily for two and a half days. One group (n=6) was then randomized to receive a single bolus of 50 IU/kg PCC (Co-fact©, Sanquin, the Netherlands) while the other group (n=6) was given a similar volume of saline. Results: The prothrombin time (PT) was significantly prolonged by Rivaroxaban (15.8 sec ± 1.3 versus 12.3 ± 0.7 at baseline; p<0.001). Immediately after the infusion of PCC, the PT normalised almost completely (12.8 ± 1.0; p<0.001), which was sustained for 24 hours. Saline did not reverse the PT prolongation (16.2 ± 0.8; p= 0.4). Furthermore, Rivaroxaban inhibited the endogenous thrombin potential (ETP) (51% ± 22, baseline 92 ± 22; p= 0.002), with normalisation after administration of PCC (114 ± 26; p<0.001), but not after saline (41 ± 6; p= 0.2). Conclusions: This study provides the first data that Prothrombin Complex Concentrate reverses the anticoagulant effect of Rivaroxaban in humans and may serve as an antidote for the new oral factor Xa inhibitors (Figure Presented) .
Original languageEnglish
JournalBlood
Volume116
Issue number21
Publication statusPublished - 19-Nov-2010

Keywords

  • prothrombin complex
  • anticoagulant agent
  • rivaroxaban
  • sodium chloride
  • blood clotting factor 10a inhibitor
  • antidote
  • placebo
  • thrombin
  • human
  • normal human
  • society
  • hematology
  • controlled study
  • animal experiment
  • Europe
  • emergency surgery
  • bleeding
  • pharmacokinetics
  • orthopedic surgery
  • venous thromboembolism
  • Canada
  • male
  • infusion
  • prothrombin time
  • Netherlands
  • prevention

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