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 provided thromboprotection as efficiently as heparin, and both drugs prevented fibrin deposition and thrombosis within the extracorporeal circuit. Unlike heparin, 3F7 treatment did not impair the hemostatic capacity and did not increase bleeding from wounds. These data establish that targeting of FXIIa is a safe mode of thromboprotection in bypass systems, and provide a clinically relevant anticoagulation strategy that is not complicated by excess bleeding.

Published in

Science Translational Medicine
2014, Volume: 6, number: 222
Publisher: AMER ASSOC ADVANCEMENT SCIENCE

SLU Authors

• Hedenqvist, Patricia

  • Department of Clinical Sciences, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Cardiac and Cardiovascular Systems
Cell and Molecular Biology


Publication identifier

DOI: https://doi.org/10.1126/scitranslmed.3006804

Permanent link to this page (URI)

https://res.slu.se/id/publ/67863