Hereditary Angioedema and Venous Thromboembolism: Where There's Smoke, There's Fire

C1-inhibitor deficiency-associated hereditary angioedema (C1INH-HAE) is a rare congenital swelling disorder caused by mutations in the SERPING1 gene. Despite evidence of a systemic procoagulant state in C1INH-HAE, dogma held that this disorder was not associated with thrombotic pathologies. Recent population scale epidemiological evidence has directly challenged this, with C1INH-HAE being associated with a significantly increased risk of venous thromboembolism (VTE). This review considers the growing body of evidence supporting associations between HAE and both a systemic procoagulant state and an increased risk of VTE. In the setting of C1INH-HAE, the relationship between the observed procoagulant and thrombotic phenotypes is a prime example of "where there's smoke, there's fire." This review also discusses the impact of C1INH-HAE disease modifying therapies on coagulation and VTE. Further, the utility of preclinical mouse models of C1-inhibitor deficiency is considered.