In Focus
Comparison of three‐factor and four‐factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers

https://doi.org/10.1111/jth.12599Get rights and content
Under an Elsevier user license
open archive

Summary

Background

Four‐factor prothrombin complex concentrates (PCCs), which contain factor II, FVII, FIX, and FX, have shown the potential to reverse the anticoagulant effect of rivaroxaban in healthy volunteers. The purpose of this study was to determine whether a three‐factor PCC, which contains little FVII, has a similar effect.

Methods and results

We performed an open‐label, single‐center, parallel‐group study comparing the effect of a three‐factor PCC (Profilnine SD) with that of a four‐factor PCC (Beriplex P/N) on the pharmacodynamics of rivaroxaban in 35 healthy volunteers. After receiving 4 days of rivaroxaban 20 mg twice daily to obtain supratherapeutic steady‐state concentrations, volunteers were randomized to receive a single 50 IU kg−1 bolus dose of four‐factor PCC, three‐factor PCC or saline 4 h after the morning dose of rivaroxaban on day 5, and the effects of these interventions on prothrombin time and thrombin generation were determined. Within 30 min, four‐factor PCC reduced mean prothrombin time by 2.5–3.5 s, whereas three‐factor PCC produced only a 0.6–1.0‐s reduction. In contrast, three‐factor PCC reversed rivaroxaban‐induced changes in thrombin generation more than four‐factor PCC.

Conclusions

This study demonstrates the potential of both three‐factor and four‐factor PCCs to at least partially reverse the anticoagulant effects of rivaroxaban in healthy adults. The discrepant effects of the PCC preparations may reflect differences in the procoagulant components present in each.

Keywords

anticoagulants
hemorrhage
pharmacology
prothrombin complex concentrates
rivaroxaban

Cited by (0)

See also Makris M. Prothrombin complex concentrate for non‐vitamin K oral anticoagulant reversal: good enough for now? J Thromb Haemost 2014; DOI: 10.1111/jth.12667

Manuscript handled by: S. Kitchen

Final decision: F. R. Rosendaal, 30 April 2014

Clinical Trial Registration: www.ClinicalTrials.gov NCT01656330