Key result
In vitro, an 80% dose of activated prothrombin complex concentrate (40 IU/kg) reversed the anticoagulant effect of apixaban more effectively than corresponding doses of rFVIIa and PCC.
Why the study?
Does aPCC reverse the anticoagulant effect of apixaban more effectively than PCC or rFVIIa in vitro?
Does aPCC reverse the anticoagulant effect of apixaban more effectively than PCC or rFVIIa in vitro?
In an in vitro model using blood from apixaban-treated patients, aPCC was superior to PCC and rFVIIa in reversing the anticoagulant effects of apixaban.
This hypothesis-generating in vitro data should not yet change practice; leaves open whether.
Unlabelled Box •An antidote for apixaban is not yet available. •We tested the effect of different haemostatic agents to reverse the apixaban effect in vitro. •Activated prothrombin complex concentrate (aPCC) was superior to prothrombin complex concentrate and recombinant activated factor VII. •Even low doses of aPCC reversed the apixaban effect completely in vitro. We acknowledge statistical assistance from Richard Lee. The anti‐Xa assays were performed at the Department of Medical Biochemistry at Oslo University Hospital.Funding: The study was financially supported by an unrestricted research grant from Bayer, Germany. Bayer Background The number of patients under treatment with FXa inhibitors is increasing, but there is no concensus on how to reverse their anticoagulant effect in case of a life‐threatening bleeding. A specific antidote is not yet commercially available. Prothrombin complex concentrate (PCC), activated PCC (aPCC) and recombinant factor VIIa (rFVIIa) are suggested available reversal agents. Objectives To find the most effective reversal agent to apixaban and to determine the optimal dose. Patients/Methods PCC, aPCC, and rFVIIa at concentrations imitating 80%, 100%, and 125% of suggested therapeutic doses were added to blood drawn from apixaban‐treated patients (n=30). aPCC was also tested in a 50% dose. Samples from healthy subjects (n=40) were used as controls. Thromboelastometry in whole blood (WB) and thrombin generation in platelet‐poor plasma (PPP) were measured to assess the reversal effect. Results aPCC shortened clotting time (CT) in WB, and increased the peak thrombin concentration and velocity index in PPP to a greater extent than PCC and rFVIIa. No significant differences were seen between rFVIIa and aPCC on thrombin generation lag time, or between PCC and aPCC on endogenous thrombin potential (ETP). The 50% dose of aPCC had a slightly inferior effect, but was comparable to the other reversal agents. Conclusions In this in vitro study the 80% dose of aPCC (40 IU/kg) reversed the anticoagulant effect of apixaban more effectively than the corresponding dose of rFVIIa and PCC both in WB (CT) and PPP (peak, ETP).
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Schultz et al. (2017) studied Apixaban-treated patients (n=70). Activated prothrombin complex concentrate (aPCC) vs. Prothrombin complex concentrate (PCC) and recombinant factor VIIa (rFVIIa) was evaluated on Reversal effect assessed by thromboelastometry in whole blood (clotting time) and thrombin generation in platelet-poor plasma. In vitro, an 80% dose of activated prothrombin complex concentrate (40 IU/kg) reversed the anticoagulant effect of apixaban more effectively than corresponding doses of rFVIIa and PCC.
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