Alpha-1 antitrypsin deficiency associated with increased risk of venous thromboembolism: a nationwide cohort study in Denmark.

BACKGROUND

Mechanistic investigations suggest that alpha-1 antitrypsin may influence hemostatic processes; however, whether alpha-1 antitrypsin deficiency is associated with an elevated risk of venous thromboembolism is unclear.

OBJECTIVES

We tested whether alpha-1 antitrypsin deficiency is associated with venous thromboembolisms in 2 large independent cohorts.

METHODS

In a nationwide nested cohort of 3046 individuals with alpha-1 antitrypsin deficiency and 29,742 controls without it matched for 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. Sixteen thousand seven hundred sixty-eight individuals being heterozygous for alpha-1 antitrypsin deficiency and 415,208 controls from the UK Biobank were used as a confirmatory cohort.

RESULTS

Compared with 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; 95% CI, 2.12-2.80). Individuals with vs 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 the 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 with those in controls.

CONCLUSION

Alpha-1 antitrypsin deficiency was associated with increased risks of pulmonary embolism, deep vein thrombosis, and venous thromboembolism in 2 independent populations.