High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism
Background - C1-inhibitor (C1INH) is a broad-acting serine protease inhibitor with anticoagulant activity. The impact of C1INH plasma levels within the normal physiological range on risk of venous thromboembolism (VTE) is unknown. We assessed the association of plasma C1INH levels and VTE risk and e...
Published in: | Journal of Thrombosis and Haemostasis |
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Online Access: | https://hdl.handle.net/10037/30166 https://doi.org/10.1016/j.jtha.2023.03.024 |
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ftunivtroemsoe:oai:munin.uit.no:10037/30166 2023-09-05T13:23:47+02:00 High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism Grover, Steven P. Snir, Omri Hindberg, Kristian Dalsbø Englebert, Tatianna M. Brækkan, Sigrid Kufaas Morelli, Vania Maris Jensen, Søren Beck Wolberg, Alisa S. Mollnes, Tom Eirik Ueland, Thor Mackman, Nigel Hansen, John Bjarne 2023-03-31 https://hdl.handle.net/10037/30166 https://doi.org/10.1016/j.jtha.2023.03.024 eng eng Elsevier Journal of Thrombosis and Haemostasis Grover, Snir, Hindberg, Englebert, Brækkan, Morelli, Jensen, Wolberg, Mollnes, Ueland, Mackman, Hansen. High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism. Journal of Thrombosis and Haemostasis. 2023 FRIDAID 2149579 doi:10.1016/j.jtha.2023.03.024 1538-7933 1538-7836 https://hdl.handle.net/10037/30166 Attribution 4.0 International (CC BY 4.0) openAccess Copyright 2023 The Author(s) https://creativecommons.org/licenses/by/4.0 Journal article Tidsskriftartikkel Peer reviewed publishedVersion 2023 ftunivtroemsoe https://doi.org/10.1016/j.jtha.2023.03.024 2023-08-23T23:07:11Z Background - C1-inhibitor (C1INH) is a broad-acting serine protease inhibitor with anticoagulant activity. The impact of C1INH plasma levels within the normal physiological range on risk of venous thromboembolism (VTE) is unknown. We assessed the association of plasma C1INH levels and VTE risk and evaluated the impact of C1INH on thrombin and plasmin generation in ex vivo assays. Methods - A nested case-control study with 405 patients with VTE and 829 age- and sex-matched controls was derived from the Tromsø Study. Odds ratios (ORs) with 95% confidence intervals (95% CI) for VTE were estimated across plasma C1INH quartiles. Genetic regulation of C1INH was explored using quantitative trait loci analysis of whole exome sequencing data. The effect of plasma C1INH levels on coagulation was evaluated ex vivo by calibrated automated thrombography. Results - Individuals with C1INH levels in the highest quartile had a lower risk of VTE (OR 0.68, 95% CI: 0.49-0.96) compared with those with C1INH in the lowest quartile. In subgroup analysis, the corresponding ORs were 0.60 (95% CI: 0.39-0.89) for deep vein thrombosis and 0.85 (95% CI: 0.52-1.38) for pulmonary embolism, respectively. No significant genetic determinants of plasma C1INH levels were identified. Addition of exogenous C1INH to normal human plasma reduced thrombin generation triggered by an activator of the intrinsic coagulation pathway, but not when triggered by an activator of the extrinsic coagulation pathway. Conclusions - High plasma levels of C1INH were associated with lower risk of VTE, and C1INH inhibited thrombin generation initiated by the intrinsic coagulation pathway ex vivo. Article in Journal/Newspaper Tromsø University of Tromsø: Munin Open Research Archive Tromsø Journal of Thrombosis and Haemostasis 21 7 1849 1860 |
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Open Polar |
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University of Tromsø: Munin Open Research Archive |
op_collection_id |
ftunivtroemsoe |
language |
English |
description |
Background - C1-inhibitor (C1INH) is a broad-acting serine protease inhibitor with anticoagulant activity. The impact of C1INH plasma levels within the normal physiological range on risk of venous thromboembolism (VTE) is unknown. We assessed the association of plasma C1INH levels and VTE risk and evaluated the impact of C1INH on thrombin and plasmin generation in ex vivo assays. Methods - A nested case-control study with 405 patients with VTE and 829 age- and sex-matched controls was derived from the Tromsø Study. Odds ratios (ORs) with 95% confidence intervals (95% CI) for VTE were estimated across plasma C1INH quartiles. Genetic regulation of C1INH was explored using quantitative trait loci analysis of whole exome sequencing data. The effect of plasma C1INH levels on coagulation was evaluated ex vivo by calibrated automated thrombography. Results - Individuals with C1INH levels in the highest quartile had a lower risk of VTE (OR 0.68, 95% CI: 0.49-0.96) compared with those with C1INH in the lowest quartile. In subgroup analysis, the corresponding ORs were 0.60 (95% CI: 0.39-0.89) for deep vein thrombosis and 0.85 (95% CI: 0.52-1.38) for pulmonary embolism, respectively. No significant genetic determinants of plasma C1INH levels were identified. Addition of exogenous C1INH to normal human plasma reduced thrombin generation triggered by an activator of the intrinsic coagulation pathway, but not when triggered by an activator of the extrinsic coagulation pathway. Conclusions - High plasma levels of C1INH were associated with lower risk of VTE, and C1INH inhibited thrombin generation initiated by the intrinsic coagulation pathway ex vivo. |
format |
Article in Journal/Newspaper |
author |
Grover, Steven P. Snir, Omri Hindberg, Kristian Dalsbø Englebert, Tatianna M. Brækkan, Sigrid Kufaas Morelli, Vania Maris Jensen, Søren Beck Wolberg, Alisa S. Mollnes, Tom Eirik Ueland, Thor Mackman, Nigel Hansen, John Bjarne |
spellingShingle |
Grover, Steven P. Snir, Omri Hindberg, Kristian Dalsbø Englebert, Tatianna M. Brækkan, Sigrid Kufaas Morelli, Vania Maris Jensen, Søren Beck Wolberg, Alisa S. Mollnes, Tom Eirik Ueland, Thor Mackman, Nigel Hansen, John Bjarne High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism |
author_facet |
Grover, Steven P. Snir, Omri Hindberg, Kristian Dalsbø Englebert, Tatianna M. Brækkan, Sigrid Kufaas Morelli, Vania Maris Jensen, Søren Beck Wolberg, Alisa S. Mollnes, Tom Eirik Ueland, Thor Mackman, Nigel Hansen, John Bjarne |
author_sort |
Grover, Steven P. |
title |
High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism |
title_short |
High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism |
title_full |
High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism |
title_fullStr |
High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism |
title_full_unstemmed |
High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism |
title_sort |
high plasma levels of c1-inhibitor are associated with lower risk of future venous thromboembolism |
publisher |
Elsevier |
publishDate |
2023 |
url |
https://hdl.handle.net/10037/30166 https://doi.org/10.1016/j.jtha.2023.03.024 |
geographic |
Tromsø |
geographic_facet |
Tromsø |
genre |
Tromsø |
genre_facet |
Tromsø |
op_relation |
Journal of Thrombosis and Haemostasis Grover, Snir, Hindberg, Englebert, Brækkan, Morelli, Jensen, Wolberg, Mollnes, Ueland, Mackman, Hansen. High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism. Journal of Thrombosis and Haemostasis. 2023 FRIDAID 2149579 doi:10.1016/j.jtha.2023.03.024 1538-7933 1538-7836 https://hdl.handle.net/10037/30166 |
op_rights |
Attribution 4.0 International (CC BY 4.0) openAccess Copyright 2023 The Author(s) https://creativecommons.org/licenses/by/4.0 |
op_doi |
https://doi.org/10.1016/j.jtha.2023.03.024 |
container_title |
Journal of Thrombosis and Haemostasis |
container_volume |
21 |
container_issue |
7 |
container_start_page |
1849 |
op_container_end_page |
1860 |
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1776204362611163136 |