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

Abstract

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] 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 rhC1INH; 2259 [586-7533] μg/l saline) and 2 h postinfusion (2389 [760-4974] μg/l rhC1INH; 2550 [310-8410] μg/l saline); median plasma D-dimer levels were decreased by Day 7 in both groups (425 [232-3240] μg/l rhC1INH; 418 [246-2318] μg/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.

• Authors: A Reshef, A Zanichelli, H Longhurst, A Relan, C E Hack
• Journal: Allergy (Allergy) Vol. 70 Issue 5 Pg. 506-13 (May 2015) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 25640891 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. Allergy Published by John Wiley & Sons Ltd.

Chemical References

• Complement C1 Inactivator Proteins
• Complement C1 Inhibitor Protein
• Fibrin Fibrinogen Degradation Products
• Recombinant Proteins
• SERPING1 protein, human
• fibrin fragment D

Topics

• Adolescent
• Adult
• Aged
• Complement C1 Inactivator Proteins (deficiency, therapeutic use)
• Complement C1 Inhibitor Protein
• Double-Blind Method
• Female
• Fibrin Fibrinogen Degradation Products (analysis)
• Hereditary Angioedema Types I and II (blood, complications)
• Humans
• Male
• Middle Aged
• Recombinant Proteins (therapeutic use)
• Thromboembolism (blood, etiology)
• Venous Thrombosis (blood, etiology)
• Young Adult