Journal article
Cardiovascular disease: A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk
M Larsson, V Rayzman, MW Nolte, KF Nickel, J Björkqvist, A Jämsä, MP Hardy, M Fries, S Schmidbauer, P Hedenqvist, M Broomé, I Pragst, G Dickneite, MJ Wilson, AD Nash, C Panousis, T Renné
Science Translational Medicine | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2014
Abstract
Currently used anticoagulants prevent thrombosis but increase bleeding. We show an anticoagulation therapy without bleeding risk based on a plasma protease factor XII function-neutralizing antibody. We screened for antibodies against activated factor XII (FXIIa) using phage display and demonstrated that recombinant fully human antibody 3F7 binds into the FXIIa enzymatic pocket. 3F7 interfered with FXIIa-mediated coagulation, abolished thrombus formation under flow, and blocked experimental thrombosis in mice and rabbits. We adapted an extracorporeal membrane oxygenation (ECMO) cardiopulmonary bypass system used for infant therapy to analyze clinical applicability of 3F7 in rabbits. 3F7 provi..
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Awarded by European Commission
Funding Acknowledgements
Funding: This work was supported in part by grants from The Crown Princess Lovisas Foundation for Sick Children to M. L., Vetenskapsradet grant (2011-6373) to P. H., and Hjart Lungfonden (20110500), Stockholms lans landsting (ALF, 2110471), Cancerfonden (100615), Vetenskapsradet (K2013-65X-21462-04-5), German Research Society (SFB 841 TP B8), and European Research Council grant (ERC-StG-2012-311575_F-12) to T.R.