Elevated D-dimers in attacks of hereditary angioedema are not associated with increased thrombotic risk

BACKGROUND: Recommended management of attacks of hereditary angioedema (HAE) due to C1 esterase inhibitor (C1-INH) deficiency (C1-INH-HAE) includes therapy with exogenous C1INH. Thrombotic/thromboembolic events (TEE) have been reported with plasma-derived C1INH, but so far none with recombinant human C1INH (rhC1INH). This phase III, randomized, placebo (saline)-controlled study evaluated the safety of rhC1INH 50 IU/kg for the treatment of acute attacks in 74 patients with C1-INH-HAE.

METHODS: Monitoring for TEE and assessment of risk of deep vein thrombosis (DVT) by the Wells prediction rule were performed, and levels of fibrin degradation products (plasma D-dimers) were assessed before study drug administration (baseline), 2 h, and 7 days posttreatment.

RESULTS: Plasma D-dimer levels were elevated in 80% of the patients (median [25th-75th percentiles]: 2149 [480-5105] mug/l; normal <250 mug/l) and were higher in patients with submucosal (abdominal, oropharyngeal-laryngeal) attacks (3095 [890-10000] mug/l; n = 29) compared with subcutaneous (peripheral, facial) attacks (960 [450-4060] mug/l; n = 35). Median plasma D-dimer levels were comparable across treatment groups at baseline (1874 [475-4568] mug/l rhC1INH; 2259 [586-7533] mug/l saline) and 2 h postinfusion (2389 [760-4974] mug/l rhC1INH; 2550 [310-8410] mug/l saline); median plasma D-dimer levels were decreased by Day 7 in both groups (425 [232-3240] mug/l rhC1INH; 418 [246-2318] mug/l saline). No increased risk of DVT was identified, nor any TEE reported in rhC1INH treated or controls.

CONCLUSION: Elevated plasma D-dimer levels were associated with acute C1-INH-HAE attacks, particularly with submucosal involvement. However, rhC1INH therapy was not associated with thrombotic events.Copyright © 2015 The Authors. Allergy Published by John Wiley & Sons Ltd.

Available from: http://onlinelibrary.wiley.com/doi/10.1111/all.12587/full