Abstract Number: VPB1019
Meeting: ISTH 2022 Congress
Theme: Coagulation and Natural Anticoagulants » Critical Care and Perioperative
Background: In patients with factor-Xa inhibitors associated bleeding, hemostatic restoration can be achieved by andexanet alfa (andexanet) or off-label use of prothrombin complex concentrate (PCC). Although thrombin generation (TG) is a golden method to monitor the effects of reversal agents, conflicting results have been reported. Only limited data is available on head-to-head comparison.
Aims: Assessing the reversal potential of andexanet and PCC in rivaroxaban-anticoagulated blood by TG and ex vivo flow chamber assays.
Methods: After ethical approval, blood samples of 6 donors were collected and spiked ex vivo with rivaroxaban (150 and 300 ng/ml). PCC (Cofact®; 25 and 50 U/kg) and andexanet (800 mg) were added at clinically recommended doses. TG was assessed with 5 pM tissue factor (TF) and 4 μM phospholipids. flow chamber experiments were performed to measure the impact on platelet aggregation and thrombus formation under high shear rate (1000 s-1) over TF and collagen (Quantification by ImageJ).
Results: Rivaroxaban prolonged the lag time and decreased endogenous thrombin potential and peak height dose-dependently. Independent of rivaroxaban concentration, andexanet normalized or overcompensated all TG parameters. PCC showed no significant improvement on TG. In flow chamber experiment, rivaroxaban (150 and 300 ng/ml) reduced platelet adhesion to 26% and 13%, and thrombus formation to 2.5% and 0.95% of baseline, respectively. Andexanet independent of anti-FXa level, restored 90% and 100% of fibrin formation after 5 and 6 min running blood flow. However, after 6 min blood flow, this efficacy for PCC (25 U/kg) was 36% and 19%, and for PCC (50 U/kg) was 72% and 61% in 150 and 300 ng/ml rivaroxaban, respectively.
Conclusion(s): Results of TG assay do not consistently predict the effectiveness of hemostatic agents in vitro. Flow chamber experiment by simulating the physiological conditions shows the efficacies of andexanet and PCC in normalization of hemostasis alterations caused by rivaroxaban.
To cite this abstract in AMA style:
Rayatdoost F, Deventer K, Schöchl H, Grottke O. Assessing the reversal efficacy of prothrombin complex concentrate (PCC) and andexanet alfa in rivaroxaban-anticoagulated blood: Ex vivo study [abstract]. https://abstracts.isth.org/abstract/assessing-the-reversal-efficacy-of-prothrombin-complex-concentrate-pcc-and-andexanet-alfa-in-rivaroxaban-anticoagulated-blood-ex-vivo-study/. Accessed March 22, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/assessing-the-reversal-efficacy-of-prothrombin-complex-concentrate-pcc-and-andexanet-alfa-in-rivaroxaban-anticoagulated-blood-ex-vivo-study/