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

BackgroundRecommended 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 50IU/kg for the treatment of acute attacks in 74 patients with C1-INH-HAE. MethodsMonitoring 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), 2h, and 7days posttreatment. ResultsPlasma D-dimer levels were elevated in 80% of the patients (median [25th-75th percentiles]: 2149 [480-5105]g/l; normal 250g/l) and were higher in patients with submucosal (abdominal, oropharyngeal-laryngeal) attacks (3095 [890-10000]g/l; n=29) compared with subcutaneous (peripheral, facial) attacks (960 [450-4060]g/l; n=35). Median plasma D-dimer levels were comparable across treatment groups at baseline (1874 [475-4568]g/l rhC1INH; 2259 [586-7533]g/l saline) and 2h postinfusion (2389 [760-4974]g/l rhC1INH; 2550 [310-8410]g/l saline); median plasma D-dimer levels were decreased by Day 7 in both groups (425 [232-3240]g/l rhC1INH; 418 [246-2318]g/l saline). No increased risk of DVT was identified, nor any TEE reported in rhC1INH treated or controls. ConclusionElevated 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.