A new study has found that higher levels of C1-inhibitor (C1INH), a deficiency of which can lead to hereditary angioedema (HAE), are associated with a reduced risk of future venous thromboembolism (VTE). The study, published in the Journal of Thrombosis and Haemostasis, also found that inhibition of C1INH inhibited ex vivo thrombin generation.

“It was recently reported that C1INH deficiency, resulting in hereditary angioedema, is associated with an increased risk of VTE,” the authors wrote. “We assessed the association of plasma C1INH levels and VTE risk, and evaluated the impact of C1INH on thrombin and plasmin generation in ex vivo assays.”

The research team conducted a nested case-control study on 405 patients with VTE and 829 age- and sex-matched controls, all from the general population. Risk estimates for VTE were estimated as a function of plasma C1INH quartiles. In addition, the authors investigated genetic regulation of C1INH levels and the impact of additional C1INH on the generation of thrombin and plasma in ex vivo assays.

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The results showed that the individuals in the highest quartile of C1INH levels had a 36% lower risk of VTE compared with those in the lowest quartile after adjusting for body mass index, C-reactive protein levels, and cancer. The authors found no specific genetic determinant of C1INH levels in the studied cohort.

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When exogenous C1INH was added to plasma in the assays, thrombin generation via the intrinsic coagulation pathway was reduced, but not via the extrinsic coagulation pathway.

The authors speculate that plasma C1INH levels could represent a reliable biomarker for future VTE risk. Clinical assays measuring C1INH antigen and activity have been developed for the diagnosis of HAE and could prove useful in this context. Furthermore, human purified and recombinant C1INH preparations that are currently employed as treatments for patients with HAE might have anticoagulant potential in the context of VTE.


Grover SP, Snir O, Hindberg K, et al. High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism. J Thromb Haemost. Published online March 31, 2023. doi:10.1016/j.jtha.2023.03.024