Abstract Number: PB0256
Meeting: ISTH 2020 Congress
Background: Coagulation factor XI (FXI) contributes to the development of thrombosis but plays only a minor role in hemostasis and is therefore an attractive target for antithrombotic therapy. Inhibition of FXIa offers the potential to reduce the risk of thrombosis without increasing the risk of bleeding. Osocimab is a fully human antibody which binds specifically to activated FXI and shows anticoagulant efficacy in vitro and in vivo. A neutralization of the anticoagulant effect might be desirable in emergency situations.
Aims: To evaluate the in vitro reversal effect of prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant activated FVII on osocimab-induced anticoagulation.
Methods: Neutralization of osocimab (0.1-1.5µM)-induced anticoagulation with prothrombin complex concentrate (Beriplex®, 0.04-5.0 U/ml), activated prothrombin complex concentrate (FEIBA®, 0.004-2.0 U/ml) and recombinant activated FVII (NovoSeven®, 0.1-1500nM) was assessed in activated partial thromboplastin time (aPTT), thrombin generation assay (TGA) in human plasma and in thromboelastometry clotting time (CT) in human whole blood in vitro.
Results: The three agents, prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant activated FVII, showed different profiles to reverse the osocimab-induced anticoagulant effects in vitro. FEIBA and rFVIIa fully reversed prolongations of aPTT and thrombeoelastometry CT, whereas PCC did not show any effect. FEIBA had a superior effect to NovoSeven and PCC in reversing the osocimab-induced changes of the thrombin generation parameters.
Conclusions: The extent of neutralization by PCC, aPCC and rVIIa was dependent on the parameter measured in osocimab-anticoagulated human plasma or blood. aPCC and rVIIa effectively neutralized most of the evaluated parameters.
To cite this abstract in AMA style:Buchmueller A, Wilmen A, Laux V. Neutralization of Osocimab-Induced Anticoagulation with Prothrombin Complex Concentrate, Activated Prothrombin Complex Concentrate and Recombinant Activated FVII in vitro [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/neutralization-of-osocimab-induced-anticoagulation-with-prothrombin-complex-concentrate-activated-prothrombin-complex-concentrate-and-recombinant-activated-fvii-in-vitro/. Accessed May 6, 2021.
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