Severe alpha-1-antitrypsin deficiency increases the risk of venous thromboembolism

Background: Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, is associated with increased risk of liver disease and chronic obstructive pulmonary disease (COPD), but the risk of venous thromboembolism (VTE) is unknown. Our aim was to evaluate the risk of VTE in individuals with severe AATD compared with control subjects from the general population. Methods: Individuals with severe AATD (n = 1577) were recruited from the Swedish national AATD register. Control subjects (n = 5969) were selected from the OLIN (Obstructive Lung Disease in Northern Sweden) studies, that include a random general population sample. Longitudinal data on VTE and diagnoses were obtained from the Swedish National Patient Registry. Associations were analyzed using multivariable Cox regression. Results: At inclusion, 46% of the AATD individuals and 53% of the controls were never-smokers. COPD was present in 46% of the AATD individuals compared with 4% of the controls. During a median follow-up of 18 years, 116 (7%) of the AATD individuals and 89 (1%) of the control subjects developed VTE, unadjusted hazard ratio 6.5 (95% confidence interval 4.9–8.6). Risk factors for incident VTE were male gender, age, COPD, cancer, and liver disease. Adjusting for these factors, the AATD individuals had a significantly higher risk of incident VTE, adjusted hazard ratio 4.2 (95% confidence interval 2.9–6.2) as compared with the controls. Conclusion: Subjects with severe AATD have considerably increased risk of developing VTE compared with the general population, even after accounting for risk factors. This calls for optimized risk factor management and clinical follow-up of this patient group.