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Elevated D ‐dimers in attacks of hereditary angioedema are not associated with increased thrombotic risk
Author(s) -
Reshef A.,
Zanichelli A.,
Longhurst H.,
Relan A.,
Hack C. E.
Publication year - 2015
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12587
Subject(s) - medicine , hereditary angioedema , d dimer , gastroenterology , saline , angioedema , thrombosis , placebo , immunology , pathology , alternative medicine
Background Recommended management of attacks of hereditary angioedema ( HAE ) due to C 1 esterase inhibitor ( C 1‐ INH ) deficiency (C1‐ INH ‐ HAE ) includes therapy with exogenous C 1 INH . Thrombotic/thromboembolic events ( TEE ) have been reported with plasma‐derived C 1 INH , but so far none with recombinant human C1 INH (rhC1 INH ). This phase III , randomized, placebo (saline)‐controlled study evaluated the safety of rhC1 INH 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] μg/l; normal ≤250 μg/l) and were higher in patients with submucosal (abdominal, oropharyngeal–laryngeal) attacks (3095 [890–10000] μg/l; n = 29) compared with subcutaneous (peripheral, facial) attacks (960 [450–4060] μg/l; n = 35). Median plasma D‐dimer levels were comparable across treatment groups at baseline (1874 [475–4568] μg/l rhC1 INH ; 2259 [586–7533] μg/l saline) and 2 h postinfusion (2389 [760–4974] μg/l rhC1 INH ; 2550 [310–8410] μg/l saline); median plasma D‐dimer levels were decreased by Day 7 in both groups (425 [232–3240] μg/l rhC1 INH ; 418 [246–2318] μg/l saline). No increased risk of DVT was identified, nor any TEE reported in rhC1 INH treated or controls. Conclusion Elevated plasma D‐dimer levels were associated with acute C1‐ INH ‐ HAE attacks, particularly with submucosal involvement. However, rhC1 INH therapy was not associated with thrombotic events.