High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism
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https://hdl.handle.net/10037/30166Date
2023-03-31Type
Journal articleTidsskriftartikkel
Peer reviewed
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 BjarneAbstract
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.