Elsevier

Thrombosis Research

Volume 133, Issue 4, April 2014, Pages 671-681
Thrombosis Research

Regular Article
Reversal of rivaroxaban-induced anticoagulation with prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant activated factor VII in vitro☆☆

https://doi.org/10.1016/j.thromres.2014.01.017Get rights and content
Under a Creative Commons license
open access

Abstract

Introduction

Anticoagulation therapies carry a risk of bleeding; reversal agents may be beneficial in cases of severe bleeding even for anticoagulants with a relatively short half-life, such as the oral factor Xa inhibitor rivaroxaban.

Materials and Methods

We investigated the in vitro reversal effect of prothrombin complex concentrate (PCC; 0.2-1.0 U/mL), activated PCC (aPCC; 0.2–1.0 U/mL) and recombinant activated factor VII (rFVIIa; 5–50 μg/mL) on rivaroxaban-induced (200–1000 ng/mL) changes in prothrombin time (PT) and thrombin generation (TG) in plasma, and in thromboelastometry (clotting time [CT]) in whole blood from healthy subjects.

Results

All three agents were partially effective in reversing rivaroxaban-induced anticoagulation but showed different profiles. rFVIIa and aPCC were more effective than PCC in reversing prolongations of PT, CT and TG lag time; rFVIIa was more effective than aPCC. However, the reversal effect reached a plateau with a maximal effect of approximately 50%. Inhibition of maximum thrombin concentration was slightly reversed by these agents; aPCC was the most effective. In contrast, inhibition of endogenous thrombin potential (ETP) was strongly reversed by aPCC, with significant increases over baseline at low rivaroxaban concentrations. Compared with aPCC, PCC showed a similar but less effective reversal profile. rFVIIa reversed ETP inhibition by approximately 50%.

Conclusions

The extent of reversal by aPCC, PCC and rFVIIa was dependent on the parameter measured in rivaroxaban-anticoagulated plasma or blood. ETP measurements may have predictive power for assessing the reversal potential of PCC or aPCC and may be used to indicate an increased prothrombotic risk.

Abbreviations

ACCP
American College of Chest Physicians
ANOVA
analysis of variance
aPCC
activated prothrombin complex concentrate
CAT
calibrated automated thrombogram
Cmax
maximum concentration (of thrombin)
CT
clotting time
DMSO
dimethyl sulphoxide
ETP
endogenous thrombin potential
INR
international normalised ratio
LMWH
low molecular weight heparin
PCC
prothrombin complex concentrate
PPP
platelet-poor plasma
PT
prothrombin time
rFVIIa
recombinant activated factor VII
SEM
standard error of the mean
TEM
thromboelastometry
TF
tissue factor
TG
thrombin generation
UFH
unfractionated heparin
VKA
vitamin K antagonist

Keywords

Recombinant activated factor VII
Antidote
Prothrombin complex concentrate
Activated prothrombin complex concentrate
Rivaroxaban

Cited by (0)

☆☆

Presented at: ICT 2012 (22nd International Congress on Thrombosis), Nice, France, October 6–9 2012.