Key result
PCC immediately normalizes rivaroxaban-induced prothrombin time prolongation versus saline, shortening PT to ~13 seconds.
Why the study?
Immediate reversal of rivaroxaban anticoagulation is required in major bleeding or emergency surgery, but no specific antidote is currently available.
Does Prothrombin Complex Concentrate reverse the anticoagulant effect of rivaroxaban in healthy male subjects?
RCT (n=12)
double-blind
randomized
Does Prothrombin Complex Concentrate reverse the anticoagulant effect of rivaroxaban in healthy male subjects?
Prothrombin Complex Concentrate effectively reverses the anticoagulant effect of rivaroxaban in healthy human subjects, providing the first evidence for its potential use as an antidote for oral factor Xa inhibitors.
Answers are grounded in this paper and cite their sources.
May support PCC for urgent rivaroxaban reversal; leaves open need for larger trials on dosing and outcomes.
Abstract 1094 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. Disclosures: Eerenberg: Sanquin Netherlands: Research Funding, make available of Prothrombin Complex Concentrate for this study. Kamphuisen:Sanquin Netherlands: Research Funding, make available of Prothrombin Complex Concentrate for this study. Levi:Sanquin Netherlands: Research Funding, make available of Prothrombin Complex Concentrate for this study.
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Eerenberg et al. (2010) conducted an RCT in Healthy volunteers (n=12). Prothrombin Complex Concentrate vs. Saline was evaluated on Prothrombin time (PT) immediately after infusion (p=< 0.001). Prothrombin Complex Concentrate immediately normalized prothrombin time prolonged by rivaroxaban in healthy male subjects (12.8 sec vs 16.2 sec for saline; p<0.001).
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