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Multiplex protein s...
Multiplex protein screening of biomarkers associated with major bleeding in patients with atrial fibrillation treated with oral anticoagulation.
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- Siegbahn, Agneta, 1947- (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Science for Life Laboratory, SciLifeLab,Klinisk kemi,UCR
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- Lindbäck, Johan (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR)
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- Hijazi, Ziad (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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- Åberg, Mikael (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab
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Alexander, John H (author)
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Eikelboom, John W (author)
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Lopes, Renato D (author)
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- Pol, Tymon (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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- Oldgren, Jonas, 1964- (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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Granger, Christopher B (author)
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Yusuf, Salim (author)
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- Wallentin, Lars, 1943- (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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(creator_code:org_t)
- John Wiley & Sons, 2021
- 2021
- English.
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In: Journal of Thrombosis and Haemostasis. - : John Wiley & Sons. - 1538-7933 .- 1538-7836. ; 19:11, s. 2726-2737
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Abstract
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- BACKGROUND: Oral anticoagulants (OAC) in patients with atrial fibrillation (AF) prevent thromboembolic events, but are associated with significant risk of bleeding.OBJECTIVES: To explore associations between a wide range of biomarkers and bleeding risk in patients with AF on OAC.METHOD: Biomarkers were analyzed in a random sample of 4200 patients, 204 cases with major bleedings, from ARISTOTLE. The replication cohort included 344 cases with major bleeding and 1024 random controls from RE-LY. Plasma samples obtained at randomization were analyzed by the Olink Proximity Extension Assay cardiovascular and inflammation panels and conventional immunoassays. The associations between biomarker levels and major bleeding over 1 to 3 years of follow-up were evaluated by random survival forest/Boruta analyses and Cox regression analyses to assess linear associations and hazard ratios for identified biomarkers.RESULTS: Out of 268 proteins, nine biomarkers were independently associated with bleeding in both cohorts. In the replication cohort the linear hazard ratios (95% confidence intervals) per interquartile range were for these biomarkers: TNF-R1 1.748 (1.456, 2.098), GDF-15 1.653 (1.377, 1.985), EphB4 1.575 (1.320, 1.880), suPAR 1.548 (1.294, 1.851), OPN 1.476 (1.240, 1.757), OPG 1.397 (1.156, 1.688), TNF-R2 1.360 (1.144,1.616), cTnT-hs 1.232 (1.067, 1.423), and TRAIL-R2 1.202 (1.069, 1.351).CONCLUSIONS: In patients with AF on OAC, GDF-15, cTnT-hs, and seven novel biomarkers were independently associated with major bleedings and reflect pathophysiologic processes of inflammation, apoptosis, oxidative stress, vascular calcification, coagulation, and fibrinolysis. Investigations of the utility of these markers to refine risk stratification and guide the management of patients at high risk of bleeding are warranted.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- anticoagulants
- atrial fibrillation
- biomarkers
- hemorrhages
- proteomics
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Siegbahn, Agneta ...
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Lindbäck, Johan
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Hijazi, Ziad
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Åberg, Mikael
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Alexander, John ...
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Eikelboom, John ...
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show more...
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Lopes, Renato D
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Pol, Tymon
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Oldgren, Jonas, ...
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Granger, Christo ...
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Yusuf, Salim
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Wallentin, Lars, ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
- Articles in the publication
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Journal of Throm ...
- By the university
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Uppsala University