Abstract Number: PB2446
Meeting: ISTH 2020 Congress
Background: Direct acting oral anticoagulants (DOACs) including Factor Xa inhibitors, are safe and effective alternatives to warfarin and the prescribing rate is increasing. There have been concerns about how to reverse their effect in case of serious bleeds or need for emergency surgery. The antidote andexanet alfa was introduced in 2018, but is still not available in all parts of the world. There are few clinical studies evaluating the reversing effect of activated prothrombin complex concentrate (aPCC) and the optimal dose is not known. Because of the feared thrombogenicity of aPCC, administration of a low dose is desireable.
Aims: To find the lowest concentration of aPCC sufficient to reverse the effect of rivaroxaban and apixaban.
Methods: Whole blood from healthy volunteers was spiked with apixaban or rivaroxaban to mimic peak concentration, and then aPCC in different concentrations ranging from 0.08-0.77 IU/mL (corresponding to doses of 5-50 IU/kg) was added. For rivaroxaban an additional dose of 1.54 IU/ml was tested. One aliquot was left untreated (baseline). We used thromboelastometry with minimal tissue factor activation and thrombin generation assay to assess the reversal effect of the different concentrations of aPCC.
Results: Apixaban and rivaroxaban increased thromboelastometry clotting time (CT) and reduced thrombin generation. aPCC improved these parameters in a concentration-dependent manner. For apixaban, aPCC at a dose of 0.15 IU/mL shortened CT to baseline level and for rivaroxaban the dose shortening CT to baseline-level was 0.46 IU/mL. The thrombin generation parameter peak thrombin concentration was not fully restored by aPCC at any dose, but both time to peak and endogenous thrombin potential (ETP) were back at baseline level at a dose of 0.46 IU/mL for both apixaban and rivaroxaban (Figure 1).
Conclusions: aPCC seems to reverse the effect of apixaban and rivaroxban at doses of 0.46 IU/mL or below.
To cite this abstract in AMA style:Schultz NH, Fareed J, Holme PA. Investigation of the Optimal Dose of aPCC in Reversing the Effect of Factor Xa Inhibitors Rivaroxaban and Apixaban- an in vitro Study [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/investigation-of-the-optimal-dose-of-apcc-in-reversing-the-effect-of-factor-xa-inhibitors-rivaroxaban-and-apixaban-an-in-vitro-study/. Accessed February 20, 2024.
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