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Intrinsic coagulation pathway-mediated thrombin generation in mouse whole blood

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Intrinsic coagulation pathway-mediated thrombin generation in mouse whole blood. / Konrath, Sandra; Mailer, Reiner K; Beerens, Manu; Englert, Hanna; Frye, Maike; Kuta, Piotr; Preston, Roger J S; Maas, Coen; Butler, Lynn M; Roest, Mark; de Laat, Bas; Renné, Thomas.

In: FRONT CARDIOVASC MED, Vol. 9, 1008410, 2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Konrath, S, Mailer, RK, Beerens, M, Englert, H, Frye, M, Kuta, P, Preston, RJS, Maas, C, Butler, LM, Roest, M, de Laat, B & Renné, T 2022, 'Intrinsic coagulation pathway-mediated thrombin generation in mouse whole blood', FRONT CARDIOVASC MED, vol. 9, 1008410. https://doi.org/10.3389/fcvm.2022.1008410

APA

Konrath, S., Mailer, R. K., Beerens, M., Englert, H., Frye, M., Kuta, P., Preston, R. J. S., Maas, C., Butler, L. M., Roest, M., de Laat, B., & Renné, T. (2022). Intrinsic coagulation pathway-mediated thrombin generation in mouse whole blood. FRONT CARDIOVASC MED, 9, [1008410]. https://doi.org/10.3389/fcvm.2022.1008410

Vancouver

Konrath S, Mailer RK, Beerens M, Englert H, Frye M, Kuta P et al. Intrinsic coagulation pathway-mediated thrombin generation in mouse whole blood. FRONT CARDIOVASC MED. 2022;9. 1008410. https://doi.org/10.3389/fcvm.2022.1008410

Bibtex

@article{f1c0d027e72b47e9ad61ae53361b7584,
title = "Intrinsic coagulation pathway-mediated thrombin generation in mouse whole blood",
abstract = "Calibrated Automated Thrombography (CAT) is a versatile and sensitive method for analyzing coagulation reactions culminating in thrombin generation (TG). Here, we present a CAT method for analyzing TG in murine whole blood by adapting the CAT assay used for measuring TG in human plasma. The diagnostically used artificial and physiologic factor XII (FXII) contact activators kaolin, ellagic acid and polyphosphate (polyP) stimulated TG in murine blood in a dose-dependent manner resulting in a gradual increase in endogenous thrombin potential and peak thrombin, with shortened lag times and times to peak. The activated FXII inhibitor rHA-Infestin-4 and direct oral anticoagulants (DOACs) interfered with TG triggered by kaolin, ellagic acid and polyP and TG was completely attenuated in blood of FXII- (F12 -/-) and FXI-deficient (F11 -/-) mice. Moreover, reconstitution of blood from F12 -/- mice with human FXII restored impaired contact-stimulated TG. HEK293 cell-purified polyP also initiated FXII-driven TG in mouse whole blood and addition of the selective inhibitor PPX_Δ12 ablated natural polyP-stimulated TG. In conclusion, the data provide a method for analysis of contact activation-mediated TG in murine whole blood. As the FXII-driven intrinsic pathway of coagulation has emerged as novel target for antithrombotic agents that are validated in mouse thrombosis and bleeding models, our novel assay could expedite therapeutic drug development.",
author = "Sandra Konrath and Mailer, {Reiner K} and Manu Beerens and Hanna Englert and Maike Frye and Piotr Kuta and Preston, {Roger J S} and Coen Maas and Butler, {Lynn M} and Mark Roest and {de Laat}, Bas and Thomas Renn{\'e}",
note = "Copyright {\textcopyright} 2022 Konrath, Mailer, Beerens, Englert, Frye, Kuta, Preston, Maas, Butler, Roest, de Laat and Renn{\'e}.",
year = "2022",
doi = "10.3389/fcvm.2022.1008410",
language = "English",
volume = "9",
journal = "FRONT CARDIOVASC MED",
issn = "2297-055X",
publisher = "Frontiers Media S. A.",

}

RIS

TY - JOUR

T1 - Intrinsic coagulation pathway-mediated thrombin generation in mouse whole blood

AU - Konrath, Sandra

AU - Mailer, Reiner K

AU - Beerens, Manu

AU - Englert, Hanna

AU - Frye, Maike

AU - Kuta, Piotr

AU - Preston, Roger J S

AU - Maas, Coen

AU - Butler, Lynn M

AU - Roest, Mark

AU - de Laat, Bas

AU - Renné, Thomas

N1 - Copyright © 2022 Konrath, Mailer, Beerens, Englert, Frye, Kuta, Preston, Maas, Butler, Roest, de Laat and Renné.

PY - 2022

Y1 - 2022

N2 - Calibrated Automated Thrombography (CAT) is a versatile and sensitive method for analyzing coagulation reactions culminating in thrombin generation (TG). Here, we present a CAT method for analyzing TG in murine whole blood by adapting the CAT assay used for measuring TG in human plasma. The diagnostically used artificial and physiologic factor XII (FXII) contact activators kaolin, ellagic acid and polyphosphate (polyP) stimulated TG in murine blood in a dose-dependent manner resulting in a gradual increase in endogenous thrombin potential and peak thrombin, with shortened lag times and times to peak. The activated FXII inhibitor rHA-Infestin-4 and direct oral anticoagulants (DOACs) interfered with TG triggered by kaolin, ellagic acid and polyP and TG was completely attenuated in blood of FXII- (F12 -/-) and FXI-deficient (F11 -/-) mice. Moreover, reconstitution of blood from F12 -/- mice with human FXII restored impaired contact-stimulated TG. HEK293 cell-purified polyP also initiated FXII-driven TG in mouse whole blood and addition of the selective inhibitor PPX_Δ12 ablated natural polyP-stimulated TG. In conclusion, the data provide a method for analysis of contact activation-mediated TG in murine whole blood. As the FXII-driven intrinsic pathway of coagulation has emerged as novel target for antithrombotic agents that are validated in mouse thrombosis and bleeding models, our novel assay could expedite therapeutic drug development.

AB - Calibrated Automated Thrombography (CAT) is a versatile and sensitive method for analyzing coagulation reactions culminating in thrombin generation (TG). Here, we present a CAT method for analyzing TG in murine whole blood by adapting the CAT assay used for measuring TG in human plasma. The diagnostically used artificial and physiologic factor XII (FXII) contact activators kaolin, ellagic acid and polyphosphate (polyP) stimulated TG in murine blood in a dose-dependent manner resulting in a gradual increase in endogenous thrombin potential and peak thrombin, with shortened lag times and times to peak. The activated FXII inhibitor rHA-Infestin-4 and direct oral anticoagulants (DOACs) interfered with TG triggered by kaolin, ellagic acid and polyP and TG was completely attenuated in blood of FXII- (F12 -/-) and FXI-deficient (F11 -/-) mice. Moreover, reconstitution of blood from F12 -/- mice with human FXII restored impaired contact-stimulated TG. HEK293 cell-purified polyP also initiated FXII-driven TG in mouse whole blood and addition of the selective inhibitor PPX_Δ12 ablated natural polyP-stimulated TG. In conclusion, the data provide a method for analysis of contact activation-mediated TG in murine whole blood. As the FXII-driven intrinsic pathway of coagulation has emerged as novel target for antithrombotic agents that are validated in mouse thrombosis and bleeding models, our novel assay could expedite therapeutic drug development.

U2 - 10.3389/fcvm.2022.1008410

DO - 10.3389/fcvm.2022.1008410

M3 - SCORING: Journal article

C2 - 36518684

VL - 9

JO - FRONT CARDIOVASC MED

JF - FRONT CARDIOVASC MED

SN - 2297-055X

M1 - 1008410

ER -