• Jerrold H Levy, Fania Szlam, and Steven Gelone.
• aDuke University School of Medicine, Durham, North Carolina bEmory University School of Medicine, Atlanta, Georgia cViroPharma Incorporated (now part of the Shire Group of Companies), Exton, Pennsylvania, ... more USA. less
• Blood Coagul. Fibrinolysis. 2014 Dec 1; 25 (8): 883-9.

AbstractHereditary angioedema (HAE) is a rare, autosomal dominant disease in which C1 esterase inhibitor (C1 INH) is deficient or dysfunctional. Package inserts for nanofiltered C1 esterase inhibitor (C1 INH-nf) products contain warnings about thrombotic events. The objective of this study was to evaluate the effect of C1 INH-nf on hemostatic activation, clot formation, and thrombin generation. Ten healthy volunteers provided blood samples for thromboelastometry using the ROTEM system. Platelet-poor samples were prepared for thrombin generation studies. C1 INH-nf was added to samples at final concentrations of 0.14, 0.7, 1.4, 2.8, and 7.0 U/ml. Recombinant factor VIIa and prothrombin complex concentrate were used as procoagulant controls, and antithrombin and desirudin were used as anticoagulant controls. C1 INH-nf had no procoagulant effect on hemostasis based on thromboelastometry, regardless of the final concentration or activating reagent used (P > 0.05 for all comparisons of C1 INH-nf versus negative control). C1 INH-nf 2.8 and 7.0 U/ml concentrations had a statistically significant anticoagulant effect on maximum clot firmness (P < 0.05 for all comparisons of C1 INH-nf versus negative control), with a magnitude similar to that observed with desirudin. C1 INH-nf had no effect on thrombin generation lag time, peak thrombin generation, or thrombin generation rate, regardless of the final concentration or activating reagent used (P < 0.05 for all comparisons of C1 INH-nf versus negative controls). We found no evidence of a procoagulant effect of C1 INH-nf when studied ex vivo at concentrations up to 10-fold higher than those achieved with clinical dosing in patients with HAE.

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