In vivo reversal of the anticoagulant effect of rivaroxaban with four-factor prothrombin complex concentrate

Stefano Barco, Y. Whitney Cheung, Michiel Coppens, Barbara A. Hutten, Joost C M Meijers, Saskia Middeldorp

Research output: Contribution to journalArticle

Abstract

Four-factor prothrombin complex concentrate (PCC) 50 iu/kg is able to swiftly restore haemostatic parameters in healthy subjects on rivaroxaban. We hypothesized that lower dosages of PCC may be sufficient to restore normal haemostasis. In this double-blind, crossover, placebo-controlled study, we compared the effects of PCC 37·5 iu/kg, PCC 25 iu/kg, and placebo on thrombin generation (endogenous thrombin potential, ETP) and prothrombin time in six healthy subjects receiving twice-daily rivaroxaban 15 mg for 2·5 days. Fifteen min after infusion of PCC 37·5 iu/kg, ETP increased from 47 ± 16% to 64 ± 22% (P = 0·03; pre-rivaroxaban ETP: 92 ± 14%) and remained higher than after placebo over 24 h (P = 0·001). PCC 25 iu/kg did not modify ETP within 15 min (53 ± 11% to 59 ± 12%; P = 0·14) and was not different from placebo over 24 h (P = 0·31). ETP reached pre-rivaroxaban levels within 6 h after PCC 37·5 iu/kg infusion and within 12-24 h after PCC 25 iu/kg infusion. Both dosages restored rivaroxaban-induced prothrombin time prolongation after 15 min (P <0·001). Placebo did not have an effect on coagulation parameters. 37·5 iu/kg of PCC leads to partial restoration of thrombin generation, whereas 25 iu/kg does not. PCC 37·5 iu/kg may be insufficient for immediate full reversal of peak therapeutic rivaroxaban levels.

Original languageEnglish
Pages (from-to)255-261
Number of pages7
JournalBritish Journal of Haematology
Volume172
Issue number2
DOIs
Publication statusPublished - Jan 1 2016

Keywords

  • Anticoagulant reversal
  • Prothrombin complex concentrate
  • Prothrombin time
  • Rivaroxaban
  • Thrombin generation

ASJC Scopus subject areas

  • Hematology

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    Barco, S., Whitney Cheung, Y., Coppens, M., Hutten, B. A., Meijers, J. C. M., & Middeldorp, S. (2016). In vivo reversal of the anticoagulant effect of rivaroxaban with four-factor prothrombin complex concentrate. British Journal of Haematology, 172(2), 255-261. https://doi.org/10.1111/bjh.13821