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Erschienen in:
01.02.2012 | Original Research Article
Recombinant C1-Inhibitor
Effects on Coagulation and Fibrinolysis in Patients with Hereditary Angioedema
Erschienen in: BioDrugs | Ausgabe 1/2012
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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.
Objectives
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 postexposure 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.
Conclusion
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.