Abstract Number: PB0451
Meeting: ISTH 2021 Congress
Background: Hemophilia is characterized by a compromised hemostatic response with delayed development of a clot and the formation of clots that are vulnerable to fibrinolysis. Emicizumab is a bispecific antibody that mimics activity of activated FVIII and increases haemostatic capacity to the level of moderate-to-mild haemophilia A. It is indicated for prophylaxis in hemophilia A patients with and without inhibitors. Despite its impressive clinical performance, breakthrough-bleeding events may still occur and management of these bleeds is challenging especially in patients with inhibitors due to increased thrombotic risk when adding bypassing therapy.
Aims: We proposed to study, in factor VIII knockout mice(FVIII-KO), whether hemostasis is improved with the addition of tranexamic acid (TxAc) to emicizumab.
Methods: FVIII-KO mice received prophylaxis with emicizumab or emicizumab+TxAc before trauma. E Emicizumab 1.5mg/kg and TxAc 0.25mg/25g was given via IV injection. A second retro-orbital IV injection containing human FIX and FX (both 100U/kg) was given 24 hours later and 5 minutes before the tail amputation or knee trauma. After knee trauma, joint bleeding was assessed using magnetic resonance imaging, histological analysis of the knee to compare the hemostastic efficacy of the two prophylactic strategies. Thrombin generation(TG) was measured and clots obtained with TG experiment were analyzed by scanning electron microscopy(SEM).
Results: In FVIII-KO mice, blood loss after tail clip was lower after prophylaxis with emicizumab+TxAc compared to emicizumab, with no statistical significance(P>0.05). However, MRI results and histological analysis of knee joints showed that the addition of TXA significantly decreased joint bleeding (3 mice had joint bleed and one mice died in the group treated with emicizumab(n=6), while 1 mice only had bleeding in the group receiving emicizumab+TxAc). SEM analysis to explore the effect of TxAc on fibrin clot quality is currently ongoing.
Conclusions: Our results suggest a potential benefit of TxAc when used in combination with emicizumab in prophylactic settings.
To cite this abstract in AMA style:Dargaud Y, Enjolras N, Janbain M, Bolbos R, Brevet M, Bordet J-. Hemostatic Effect of Tranexamic Acid Combined with Emicizumab in Prophylactic Setting in Severe Hemophilia A: A Preclinical Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/hemostatic-effect-of-tranexamic-acid-combined-with-emicizumab-in-prophylactic-setting-in-severe-hemophilia-a-a-preclinical-study/. Accessed March 4, 2024.
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