Abstract
BackgroundAn increasing number of patients are treated with direct-acting oral anticoagulants (DOACs), but the optimal way to reverse the anticoagulant effect is not known. Specific antidotes are not available and prothrombin complex concentrate (PCC), activated PCC (aPCC) and recombinant factor VIIa (rFVIIa) are variously used as reversal agents in case of a major bleeding. We aimed to determine the most effective haemostatic agent and dose to reverse the effect of rivaroxaban in blood samples from patients taking rivaroxaban for therapeutic reasons.MethodsBlood samples from rivaroxaban-treated patients (n = 50) were spiked with PCC, aPCC and rFVIIa at concentrations imitating 80%, 100% and 125% of suggested therapeutic doses. The reversal effect was assessed by thromboelastometry in whole blood and a thrombin generation assay (TGA) in platelet-poor plasma. Samples from healthy subjects (n = 40) were included as controls.ResultsIn thromboelastometry measurements, aPCC and rFVIIa had a superior effect to PCC in reversing the rivaroxaban-induced lenghtening of clotting time (CT). aPCC was the only haemostatic agent that shortened the CT down to below the control level. Compared to healthy controls, patients on rivaroxaban also had a prolonged lag time and decreased peak concentration, velocity index and endogenous thrombin potential (ETP) in platelet-poor plasma. aPCC reversed these parameters more effectively than rFVIIa and PCC. There were no differences in efficacy between 80%, 100% and 125% doses of aPCC.ConclusionsaPCC seems to reverse the anticoagulant effect of rivaroxaban more effectively than rFVIIa and PCC by evaluation with thromboelastometry and TGA in vitro.
Highlights
An increasing number of patients are treated with direct-acting oral anticoagulants (DOACs), but the optimal way to reverse the anticoagulant effect is not known
It has been shown that different prothrombin complex concentrate (PCC) incompletely reverse the anticoagulation effect of rivaroxaban on the thrombin generation assay (TGA) parameter endogenous thrombin potential (ETP) [21], and there is increasing evidence suggesting that activated PCC (aPCC) and recombinant factor VIIa (rFVIIa) have a better effect [14, 17, 19]
Rivaroxaban concentrations were compared to thromboelastometry parameters in whole blood and to TGA parameters in Platelet-poor plasma (PPP)
Summary
An increasing number of patients are treated with direct-acting oral anticoagulants (DOACs), but the optimal way to reverse the anticoagulant effect is not known. Specific antidotes are not available and prothrombin complex concentrate (PCC), activated PCC (aPCC) and recombinant factor VIIa (rFVIIa) are variously used as reversal agents in case of a major bleeding. Haemophiliacs with inhibitors are treated with recombinant activated factor VII (rFVIIa) and/or activated PCC (aPCC) containing coagulation factors II, IX, and X, and FVIIa. Several studies have evaluated the reversing effect of these surrogate antidotes on haemostatic parameters in animals [12, 13] and by using blood from healthy subjects taking rivaroxaban or blood spiked with rivaroxaban ex vivo [14,15,16,17,18,19,20]. The reversing effect of those agents has not yet been studied on patients taking rivaroxaban for therapeutic reasons
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