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Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation

Aim: Feedback activation of factor XI (FXI) by thrombin is believed to play a critical role in the amplification phase of thrombin generation and to contribute to thrombosis development and hemostasis. However, the activation of FXI by thrombin has been shown in vitro to require a cofactor. In this...

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Autores principales: Rühl, Heiko, Friemann, Anne M., Reda, Sara, Schwarz, Nadine, Winterhagen, Franziska I., Berens, Christina, Müller, Jens, Oldenburg, Johannes, Pötzsch, Bernd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Japan Atherosclerosis Society 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8737067/
https://www.ncbi.nlm.nih.gov/pubmed/33298665
http://dx.doi.org/10.5551/jat.59873
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author Rühl, Heiko
Friemann, Anne M.
Reda, Sara
Schwarz, Nadine
Winterhagen, Franziska I.
Berens, Christina
Müller, Jens
Oldenburg, Johannes
Pötzsch, Bernd
author_facet Rühl, Heiko
Friemann, Anne M.
Reda, Sara
Schwarz, Nadine
Winterhagen, Franziska I.
Berens, Christina
Müller, Jens
Oldenburg, Johannes
Pötzsch, Bernd
author_sort Rühl, Heiko
collection PubMed
description Aim: Feedback activation of factor XI (FXI) by thrombin is believed to play a critical role in the amplification phase of thrombin generation and to contribute to thrombosis development and hemostasis. However, the activation of FXI by thrombin has been shown in vitro to require a cofactor. In this study, the role of thrombin in activated FXI (FXIa) formation in vivo is investigated. Methods: The study population comprised probands in whom coagulation activation was triggered by low-dose (15 µg/kg) recombinant activated factor VII (rFVIIa, n =89), of whom 34 with (VTE+) and 45 without a history of venous thromboembolism (VTE−), and patients undergoing major orthopedic surgeries ( n =45). FXIa was quantified via an enzyme capture assay using a monoclonal FXI-specific antibody. Thrombin formation was monitored using an oligonucleotide-based enzyme capture assay and the thrombin activation markers prothrombin fragment 1+2 (F1+2) and thrombin–antithrombin complex (TAT). Results: In the rFVIIa cohort, FXIa and thrombin remained below their lower limit of quantification of 3.48 and 1.06 pmol/L, respectively. By contrast, during the surgeries, median FXIa levels increased from 3.69 pmol/L pre-operatively to 9.41 pmol/L mid-operatively ( P =4·10 (−4) ) and remained significantly elevated 24 h thereafter, with 9.38 pmol/L ( P =0.001). Peak levels of F1+2 were comparable in the VTE+, VTE−, and surgery cohort (235, 268, and 253 pmol/L), whereas peak TAT levels were higher in the surgery cohort (53.1, 33.9, and 147.6 pmol/L). Conclusions: Under in vivo conditions, the activation of FXI requires specific local features that are present at the wounded site including potential cofactors of thrombin.
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spelling pubmed-87370672022-01-25 Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation Rühl, Heiko Friemann, Anne M. Reda, Sara Schwarz, Nadine Winterhagen, Franziska I. Berens, Christina Müller, Jens Oldenburg, Johannes Pötzsch, Bernd J Atheroscler Thromb Original Article Aim: Feedback activation of factor XI (FXI) by thrombin is believed to play a critical role in the amplification phase of thrombin generation and to contribute to thrombosis development and hemostasis. However, the activation of FXI by thrombin has been shown in vitro to require a cofactor. In this study, the role of thrombin in activated FXI (FXIa) formation in vivo is investigated. Methods: The study population comprised probands in whom coagulation activation was triggered by low-dose (15 µg/kg) recombinant activated factor VII (rFVIIa, n =89), of whom 34 with (VTE+) and 45 without a history of venous thromboembolism (VTE−), and patients undergoing major orthopedic surgeries ( n =45). FXIa was quantified via an enzyme capture assay using a monoclonal FXI-specific antibody. Thrombin formation was monitored using an oligonucleotide-based enzyme capture assay and the thrombin activation markers prothrombin fragment 1+2 (F1+2) and thrombin–antithrombin complex (TAT). Results: In the rFVIIa cohort, FXIa and thrombin remained below their lower limit of quantification of 3.48 and 1.06 pmol/L, respectively. By contrast, during the surgeries, median FXIa levels increased from 3.69 pmol/L pre-operatively to 9.41 pmol/L mid-operatively ( P =4·10 (−4) ) and remained significantly elevated 24 h thereafter, with 9.38 pmol/L ( P =0.001). Peak levels of F1+2 were comparable in the VTE+, VTE−, and surgery cohort (235, 268, and 253 pmol/L), whereas peak TAT levels were higher in the surgery cohort (53.1, 33.9, and 147.6 pmol/L). Conclusions: Under in vivo conditions, the activation of FXI requires specific local features that are present at the wounded site including potential cofactors of thrombin. Japan Atherosclerosis Society 2022-01-01 2020-12-09 /pmc/articles/PMC8737067/ /pubmed/33298665 http://dx.doi.org/10.5551/jat.59873 Text en 2022 Japan Atherosclerosis Society https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.http://creativecommons.org/licenses/by-nc-sa/4.0/ (https://creativecommons.org/licenses/by-nc-sa/4.0/)
spellingShingle Original Article
Rühl, Heiko
Friemann, Anne M.
Reda, Sara
Schwarz, Nadine
Winterhagen, Franziska I.
Berens, Christina
Müller, Jens
Oldenburg, Johannes
Pötzsch, Bernd
Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation
title Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation
title_full Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation
title_fullStr Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation
title_full_unstemmed Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation
title_short Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation
title_sort activated factor xi is increased in plasma in response to surgical trauma but not to recombinant activated fvii-induced thrombin formation
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8737067/
https://www.ncbi.nlm.nih.gov/pubmed/33298665
http://dx.doi.org/10.5551/jat.59873
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