title: 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.
  
  
  CONCLUSIONS
  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: Sheba Medical Center, University of Tel Aviv, Tel-Hashomer, Israel.
authors: A
authors: A
authors: Reshef
authors: A
authors: A
authors: Zanichelli
authors: H
authors: H
authors: Longhurst
authors: A
authors: A
authors: Relan
authors: C E
authors: CE
authors: Hack
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003174:Complement C1 Inactivator Proteins / Q000172:deficiency / Q000627:therapeutic use; D050718:Complement C1 Inhibitor Protein; D004311:Double-Blind Method; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D056829:Hereditary Angioedema Types I and II / Q000097:blood* / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D013923:Thromboembolism / Q000097:blood* / Q000209:etiology; D020246:Venous Thrombosis / Q000097:blood* / Q000209:etiology; D055815:Young Adult
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D005338:Fibrin Fibrinogen Degradation Products; D011994:Recombinant Proteins; C469952:SERPING1 protein, human; C036309:fibrin fragment D
keywords: C1 esterase inhibitor; D-dimer; fibrinolysis; hereditary angioedema; thromboembolism
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