| Title: | Alpha-1 antitrypsin deficiency associated with increased risk of venous thromboembolism: a nationwide cohort study in Denmark |
| Journal: | Research and Practice in Thrombosis and Haemostasis |
| Published: | 1 Jul 2026 |
| DOI: | https://doi.org/10.1016/j.rpth.2026.106827 |
Publication 20474
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Abstract
Background Mechanistic investigations suggest that alpha-1 antitrypsin may influence hemostatic processes; however, whether alpha-1 antitrypsin deficiency is associated with elevated risk of venous thromboembolism is unclear. Objectives We tested whether alpha-1 antitrypsin deficiency is associated with venous thromboembolisms in two large independent cohorts. Methods In a nationwide nested cohort of 3,046 individuals with alpha-1 antitrypsin deficiency and 29,742 controls without alpha-1 antitrypsin deficiency matched on sex, age and municipality, we recorded admissions and deaths due to pulmonary embolism, and admissions due to deep vein thrombosis and venous thromboembolism during a median follow-up time of up to 61 years. 16,768 individuals being heterozygous for alpha-1 antitrypsin deficiency and 415,208 controls from the United Kingdom (UK) Biobank were used as a confirmatory cohort. Results Compared to controls, individuals with alpha-1 antitrypsin deficiency had increased risks of pulmonary embolism (adjusted hazard ratio: 3.28, 95% CI: 2.73-3.94), pulmonary embolism-specific mortality (2.83, 95% CI: 1.65-4.84), deep vein thrombosis (1.85, 95% CI: 1.53-2.25), and venous thromboembolism (2.43, 2.12-2.80). Individuals with versus without alpha-1 antitrypsin deficiency also had an increased use of the direct oral anticoagulants apixaban (1.83, 95% CI: 1.30-2.56) and rivaroxaban (1.49, 95% CI: 1.11-1.99). The association between heterozygosity of alpha-1 antitrypsin deficiency and pulmonary embolism, deep vein thrombosis, and venous thromboembolism was confirmed in the UK Biobank. Moreover, hospitalization rates for these conditions were higher in individuals heterozygous for alpha-1 antitrypsin deficiency compared to controls. Conclusion Alpha-1 antitrypsin deficiency was associated with increased risks of pulmonary embolism, deep vein thrombosis, and venous thromboembolism in two independent populations.</p>
6 Authors
- Sine Voss David
- Malin Fromme
- Katharina Remih
- Børge Grønne Nordestgaard
- Pavel Strnad
- Morten Dahl
1 Application
| Application ID | Title |
|---|---|
| 148742 | Multiomic signature of digestive disorders |
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