title: Recombinant C1-inhibitor: effects on coagulation and fibrinolysis in patients with hereditary angioedema.
abstract: BACKGROUND
  Recombinant human C1-inhibitor (rhC1INH; Ruconest®) has been developed for treatment of acute angioedema attacks in patients with hereditary angioedema (HAE) due to heterozygous deficiency of C1INH. Previous reports suggest that administration of plasma-derived C1INH products may be associated with an increased risk for thromboembolic complications.
  
  
  OBJECTIVE
  Our aim is to evaluate the effects of rhC1INH on coagulation and fibrinolysis in symptomatic HAE patients.
  
  
  METHODS
  Levels of various coagulation and fibrinolytic parameters were determined in pre- and post-exposure plasma samples from HAE patients included in a randomized clinical trial. Patients were treated with either saline, or 50 or 100 U/kg rhC1INH for an acute angioedema attack.
  
  
  RESULTS
  Prior to rhC1INH treatment, the majority of patients had low to normal activated partial thromboplastin times (aPTT) and increased levels of prothrombin fragment 1+2, thrombin-antithrombin complexes, D-dimers and plasmin-antiplasmin complexes, all of which indicate activation of both coagulation and fibrinolysis. Infusion of rhC1INH at doses up to 100 U/kg did not affect these parameters except for a dose-dependent prolongation of aPTT, confirming that rhC1INH is an inhibitor of the contact system, and that F1+2 levels decreased.
  
  
  CONCLUSIONS
  Coagulation and fibrinolytic systems are activated in HAE patients suffering from an acute angioedema attack. Treatment with rhC1INH at 50 or 100 U/kg had no effect on parameters reflecting activation of these systems except for a significant effect on aPTT, which likely reflects a pharmacodynamic effect of rhC1INH, and a reduction on plasma levels of the prothrombin activation fragment F1+2. We conclude that these results argue against a prothrombotic effect of treatment with this rhC1INH product in HAE patients.
authors.affiliation: Pharming Technologies BV, Leiden, the Netherlands.
authors.forename: Anurag
authors.initials: A
authors.lastname: Relan
authors.forename: Kamran
authors.initials: K
authors.lastname: Bakhtiari
authors.forename: Edwin S
authors.initials: ES
authors.lastname: van Amersfoort
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: C Erik
authors.initials: CE
authors.lastname: Hack
mesh_terms: D000293:Adolescent; D000328:Adult; D054179:Angioedemas, Hereditary / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D001777:Blood Coagulation / Q000187:drug effects*; D050718:Complement C1 Inhibitor Protein / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013923:Thromboembolism / Q000139:chemically induced*
chemical_list: D050718:Complement C1 Inhibitor Protein; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; C571093:conestat alfa