The association between hereditary angioedema (HAE) and venous thromboembolism (VTE) may be more prominent than initially thought, according to a study recently published in the Journal of Thrombosis and Haemostasis.

“In summary, the present study indicates that patients with HAE have a significantly increased risk of composite VTE but not composite [arterial thromboembolism (ATE)],” the authors wrote.

This research letter evaluated the association between HAE and thromboembolic events in both arteries and veins. Positive relationships between HAE and autoimmune and cardiovascular diseases are already evident in past literature reviews.

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Patients with HAE showcased a higher risk of developing VTE, with odds ratios of 4.20 and 3.57 in previous and current publications, respectively. The documented VTE included thrombophlebitis and portal vein thrombosis, while deep vein thrombosis and pulmonary embolism demonstrated a similar pattern. 

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HAE was further associated with a subset of ATE, with an odds ratio of 6.74 in previous research, although this analysis obtained a weaker association with an odds ratio of 1.3 for arterial thrombosis and embolism excluding coronary, cerebral, and carotid vessels. Interestingly, no increased risk could be determined for myocardial or cerebral ischemia.

The impaired activity of C1-inhibitor (C1INH) could be the mechanism behind the association between HAE and VTE, specifically due to its capacity as an inhibitor of plasma kallikrein and the intrinsic coagulation pathway. 

Moreover, although individuals with HAE in remission exhibit higher levels of coagulation biomarkers such as thrombin-antithrombin complex, prothrombin fragment 1+2, and D-dimer, levels of these components evidently increase in acute attacks. Elevated D-dimer levels are also usually present in diseases with VTE, reinforcing the relationship between both pathologies. 

Furthermore, C1INH replacement therapeutic strategies are a known effective method to prevent acute HAE attacks while also inducing a clear decrease in prothrombin fragment 1+2 and D-dimer levels. 

“More strikingly, HAE patients receiving C1INH replacement therapy administered acutely or as intermittent prophylaxis had a significantly reduced incidence of VTE compared to HAE patients not receiving therapy,” the authors wrote.


Grover SP, Sundler Björkman L, Egesten A, Moll S, Mackman N. Hereditary angioedema is associated with an increased risk of venous thromboembolism. J Thromb Haemost. Published online September 2, 2022. doi:10.1111/jth.15870