Anticoagulation With an Inhibitor of Factors XIa and XIIa During Cardiopulmonary Bypass

[en] Background: Exposure of blood to polyanionic artificial surfaces, for example, during cardiopulmonary bypass (CPB), induces a highly procoagulant condition requiring strong anticoagulation. Unfractionated heparin (UFH) is currently used during CPB but can lead to serious bleeding complications or development of a hypercoagulable state culminating in life-threatening thrombosis, highlighting the need for safer antithrombotics. Ixodes ricinus contact phase inhibitor (Ir-CPI) is a protein expressed by I. ricinus ticks, which specifically inhibits both factors XIIa and XIa, 2 factors contributing to thrombotic disease while playing a limited role in hemostasis. Objectives: This study assessed the antithrombotic activity of Ir-CPI in animal contact phase-initiated thrombosis models, including CPB. The safety of Ir-CPI also was evaluated. Methods: The authors evaluated the antithrombotic activity of Ir-CPI by using in vitro catheter-induced clotting assays and rabbit experimental models of catheter occlusion and arteriovenous shunt. During CPB with cardiac surgery in sheep, the clinical applicability of Ir-CPI was investigated and its efficacy compared to that of UFH using an uncoated system suitable for adult therapy. Taking advantage of the similar hemostatic properties of pigs and humans, the authors performed pig liver bleeding assays to evaluate the safety of Ir-CPI. Results: Ir-CPI prevented clotting in catheter and arteriovenous shunt rabbit models. During CPB, Ir-CPI was as efficient as UFH in preventing clot formation within the extracorporeal circuit and maintained physiological parameters during and post-surgery. Unlike UFH, Ir-CPI did not promote bleeding. Conclusions: Preclinical animal models used in this study showed that Ir-CPI is an effective and safe antithrombotic agent that provides a clinically relevant approach to thrombosis prevention in bypass systems, including highly thrombogenic CPB. © 2019 The Authors

Disciplines :

Cardiovascular & respiratory systems

Author, co-author :

Pireaux, V.; Bioxodes S.A., Marche-en-Famenne, Belgium

Tassignon, J.; Bioxodes S.A., Marche-en-Famenne, Belgium

Demoulin, S.; Bioxodes S.A., Marche-en-Famenne, Belgium

Derochette, S.; Bioxodes S.A., Marche-en-Famenne, Belgium

Borenstein, N.; IMM Recherche, Institut Mutualiste Montsouris, Paris, France

Ente, A.; IMM Recherche, Institut Mutualiste Montsouris, Paris, France

Fiette, L.; IMM Recherche, Institut Mutualiste Montsouris, Paris, France

Douxfils, J.; QUALIblood S.A., Namur, Belgium

Lancellotti, Patrizio ; Université de Liège - ULiège > Département des sciences cliniques > Cardiologie - Pathologie spéciale et réhabilitation

Guyaux, M.; Bioxodes S.A., Marche-en-Famenne, Belgium

Godfroid, E.; Bioxodes S.A., Marche-en-Famenne, Belgium

Language :

English

Title :

Anticoagulation With an Inhibitor of Factors XIa and XIIa During Cardiopulmonary Bypass

Publication date :

2019

Journal title :

Journal of the American College of Cardiology

ISSN :

0735-1097

eISSN :

1558-3597

Publisher :

Elsevier USA

Volume :

Issue :

Pages :

2178-2189

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 08 June 2020

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