@article{8cd8484f780b450ea2fa0c130e58721e,
title = "Thrombin generation by calibrated automated thrombography in goat plasma: Optimization of an assay",
abstract = "The goat model of atrial fibrillation (AF) allows investigation of the effect of AF on coagulation. However, assays for goat plasma are not available from commercial sources. Calibrated automated thrombography (CAT) provides a global view of the coagulation profile by assessing in vitro thrombin generation (TG). We describe the customization of the CAT assay in goat platelet-poor plasma (PPP) and in factor Xa (FXa)-inhibitor-anticoagulated PPP. TG was initiated in the presence of phospholipids and either (a) PPP reagent, reagent low, or reagent high; (b) goat brain protein extraction (GBP); or (c) Russell's viper venom-factor X activator (RVV-X). Contact activation was assessed by adding corn trypsin inhibitor. Different concentrations of prothrombin complex concentrate (PCC) were used to determine the sensitivity of both the GBP and RVV-X method. To obtain FXa-inhibitor anticoagulated plasma, rivaroxaban was added to plasma. TG settings with human reagents were not suitable for goat plasma. TG triggered with GBP increased peak height and ETP values. Similarly, the RVV-X method produced comparable TG curves and was more sensitive to PCC titration. Finally, both methods were able to detect the decrease in clotting potential induced by FXa inhibition. This is the first study that reports the customization of the CAT assay for goats. The GBP and RVV-X methods were comparable in triggering TG in goat plasma. The RVV-X method seemed to better discriminate changes in TG curves due to increases in clotting potential as well as to FXa inhibition by rivaroxaban in goat plasma.",
keywords = "goat, plasma, rivaroxaban, thrombin generation, thrombography, ATRIAL-FIBRILLATION, TISSUE FACTOR, HYPERCOAGULABILITY, MECHANISMS, STATE, RISK",
author = "Elisa D'Alessandro and Billy Scaf and {van Oerle}, Rene and {van Nieuwenhoven}, {Frans A} and {van Hunnik}, Arne and Sander Verheule and Ulrich Schotten and {Ten Cate}, Hugo and Spronk, {Henri M H}",
note = "Funding Information: H.t.C. received consultancy fees from Bayer, Pfizer, Leo, and Portola/Alexion and received research grants from Bayer, unrelated to the present work. H.t.C. is a consultant for Alveron and shareholder of CoagulationProfile, a spin‐off company of Maastricht University. U.S. received consultancy fees or honoraria from Universit{\`a} della Svizzera Italiana (USI, Switzerland), Roche Diagnostics (Switzerland), EP Solutions Inc. (Switzerland), Johnson & Johnson Medical Limited (United Kingdom), and Bayer Healthcare (Germany). U.S. received research grants from Roche and EP Solutions. Bayer Healthcare (Germany) supported pharmacokinetic study of this investigation. U.S. is cofounder and shareholder of YourRhythmics BV, a spin‐off company of University Maastricht. Funding Information: This work was supported by grants of the Netherlands Heart Foundation (CVON2014-09, RACE V Reappraisal of Atrial Fibrillation: Interaction between hyperCoagulability, Electrical remodeling, and Vascular Destabilisation in the Progression of AF), and the European Union (ITN Network Personalize AF: Personalized Therapies for Atrial Fibrillation: a translational network, grant number 860974; CATCH ME: Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly, grant number 633196; MAESTRIA: Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation, grant number 965286; REPAIR: Restoring cardiac mechanical function by polymeric artificial muscular tissue, grant number 952166). Funding Information: This work was supported by grants of the Netherlands Heart Foundation (CVON2014‐09, RACE V Reappraisal of Atrial Fibrillation: Interaction between hyperCoagulability, Electrical remodeling, and Vascular Destabilisation in the Progression of AF), and the European Union (ITN Network Personalize AF: Personalized Therapies for Atrial Fibrillation: a translational network, grant number 860974; CATCH ME: Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly, grant number 633196; MAESTRIA: Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation, grant number 965286; REPAIR: Restoring cardiac mechanical function by polymeric artificial muscular tissue, grant number 952166). Publisher Copyright: {\textcopyright} 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).",
year = "2021",
month = dec,
doi = "10.1002/rth2.12620",
language = "English",
volume = "5",
journal = "Research and practice in thrombosis and haemostasis",
issn = "2475-0379",
publisher = "Wiley",
number = "8",
}