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High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism.
Grover, Steven P; Snir, Omri; Hindberg, Kristian; Englebert, Tatianna M; Braekkan, Sigrid K; Morelli, Vânia M; Jensen, Søren B; Wolberg, Alisa S; Mollnes, Tom Eirik; Ueland, Thor; Mackman, Nigel; Hansen, John-Bjarne.
Afiliação
  • Grover SP; Division of Hematology, Department of Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill, North Carolina, USA. Electronic address: https://twitter.com/StevenPGrover.
  • Snir O; Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
  • Hindberg K; Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway. Electronic address: https://twitter.com/KristianHindbe1.
  • Englebert TM; Division of Hematology, Department of Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill, North Carolina, USA. Electronic address: https://twitter.com/OlsonTatianna.
  • Braekkan SK; Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway. Electronic address: Sigrid.brakkan@uit.no.
  • Morelli VM; Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
  • Jensen SB; Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
  • Wolberg AS; Department of Pathology and Laboratory Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill, North Carolina, USA. Electronic address: https://twitter.com/aswolberg.
  • Mollnes TE; Research Laboratory, Nordland Hospital, Bodø, Norway; Department of Immunology, Oslo University Hospital and University of Oslo, Norway; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.
  • Ueland T; Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: https://twitt
  • Mackman N; Division of Hematology, Department of Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill, North Carolina, USA. Electronic address: https://twitter.com/NMackman.
  • Hansen JB; Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
J Thromb Haemost ; 21(7): 1849-1860, 2023 07.
Article em En | MEDLINE | ID: mdl-37003465
ABSTRACT

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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Serpinas / Tromboembolia Venosa Tipo de estudo: Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Thromb Haemost Assunto da revista: HEMATOLOGIA Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Serpinas / Tromboembolia Venosa Tipo de estudo: Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Thromb Haemost Assunto da revista: HEMATOLOGIA Ano de publicação: 2023 Tipo de documento: Article