title: Effects of a plasma-derived C1 esterase inhibitor on hemostatic activation, clot formation, and thrombin generation.
abstract: Hereditary 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.
authors.affiliation: 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, USA.
authors.forename: Jerrold H
authors.initials: JH
authors.lastname: Levy
authors.forename: Fania
authors.initials: F
authors.lastname: Szlam
authors.forename: Steven
authors.initials: S
authors.lastname: Gelone
mesh_terms: D000925:Anticoagulants / Q000737:chemistry; D000991:Antithrombins / Q000737:chemistry; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000737:chemistry; D003029:Coagulants / Q000737:chemistry; D003174:Complement C1 Inactivator Proteins / Q000737:chemistry*; D050718:Complement C1 Inhibitor Protein / Q000737:chemistry*; D015942:Factor VIIa / Q000737:chemistry; D006629:Hirudins / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D010949:Plasma / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013916:Thrombelastography; D013918:Thrombin Time
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001779:Blood Coagulation Factors; D003029:Coagulants; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D006629:Hirudins; D011994:Recombinant Proteins; C025667:prothrombin complex concentrates; C103587:recombinant FVIIa; D015942:Factor VIIa; C060225:desirudin