A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk

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A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk. / Larsson, Magnus; Rayzman, Veronika; Nolte, Marc W; Nickel, Katrin F; Björkqvist, Jenny; Jämsä, Anne; Hardy, Matthew P; Fries, Marion; Schmidbauer, Stefan; Hedenqvist, Patricia; Broomé, Michael; Pragst, Ingo; Dickneite, Gerhard; Wilson, Michael J; Nash, Andrew D; Panousis, Con; Renné, Thomas.

in: SCI TRANSL MED, Jahrgang 6, Nr. 222, 05.02.2014, S. 222ra17.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

Harvard

Larsson, M, Rayzman, V, Nolte, MW, Nickel, KF, Björkqvist, J, Jämsä, A, Hardy, MP, Fries, M, Schmidbauer, S, Hedenqvist, P, Broomé, M, Pragst, I, Dickneite, G, Wilson, MJ, Nash, AD, Panousis, C & Renné, T 2014, 'A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk', SCI TRANSL MED, Jg. 6, Nr. 222, S. 222ra17. https://doi.org/10.1126/scitranslmed.3006804

APA

Larsson, M., Rayzman, V., Nolte, M. W., Nickel, K. F., Björkqvist, J., Jämsä, A., Hardy, M. P., Fries, M., Schmidbauer, S., Hedenqvist, P., Broomé, M., Pragst, I., Dickneite, G., Wilson, M. J., Nash, A. D., Panousis, C., & Renné, T. (2014). A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk. SCI TRANSL MED, 6(222), 222ra17. https://doi.org/10.1126/scitranslmed.3006804

Vancouver

Bibtex

@article{60820c49ea4f4bb8ba44bec07cd78b7a,
title = "A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk",
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.",
author = "Magnus Larsson and Veronika Rayzman and Nolte, {Marc W} and Nickel, {Katrin F} and Jenny Bj{\"o}rkqvist and Anne J{\"a}ms{\"a} and Hardy, {Matthew P} and Marion Fries and Stefan Schmidbauer and Patricia Hedenqvist and Michael Broom{\'e} and Ingo Pragst and Gerhard Dickneite and Wilson, {Michael J} and Nash, {Andrew D} and Con Panousis and Thomas Renn{\'e}",
year = "2014",
month = feb,
day = "5",
doi = "10.1126/scitranslmed.3006804",
language = "English",
volume = "6",
pages = "222ra17",
journal = "SCI TRANSL MED",
issn = "1946-6234",
publisher = "AMER ASSOC ADVANCEMENT SCIENCE",
number = "222",

}

RIS

TY - JOUR

T1 - A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk

AU - Larsson, Magnus

AU - Rayzman, Veronika

AU - Nolte, Marc W

AU - Nickel, Katrin F

AU - Björkqvist, Jenny

AU - Jämsä, Anne

AU - Hardy, Matthew P

AU - Fries, Marion

AU - Schmidbauer, Stefan

AU - Hedenqvist, Patricia

AU - Broomé, Michael

AU - Pragst, Ingo

AU - Dickneite, Gerhard

AU - Wilson, Michael J

AU - Nash, Andrew D

AU - Panousis, Con

AU - Renné, Thomas

PY - 2014/2/5

Y1 - 2014/2/5

N2 - 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.

AB - 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.

U2 - 10.1126/scitranslmed.3006804

DO - 10.1126/scitranslmed.3006804

M3 - SCORING: Journal article

C2 - 24500405

VL - 6

SP - 222ra17

JO - SCI TRANSL MED

JF - SCI TRANSL MED

SN - 1946-6234

IS - 222

ER -