Elevated thrombin generation and factor VIII activity during angioedema attack in patients with hereditary C1 inhibitor deficiency

Abstract

The ethics committee of Jagiellonian University in Kraków approved the study and patients signed a written informed consent form. The study was carried out in accordance with the Declaration of Helsinki and its amendments. Laboratory investigations Blood samples (vol/vol, 9:1 of 3.2% trisodium citrate) were spun at 2000 g for 10 minutes, and the supernatants were aliquoted and stored at a temperature of-80ºC. Plasma levels of the C1INH antigen (aC1INH) were measured using nephelometry (Siemens Healthcare Diagnostics GmbH, Marburg, Germany). The functional activity of C1INH was determined using the functional chromogenic assay Berichrom C1INH (Siemens Healthcare Diagnostics). All patients had reduced serum C1INH levels (mean, 0.07 g/l; reference range, 0.21-0.39 g/l) and functional activity of C1INH (mean functional activity of C1INH, 26.0%; reference range, 70%-130%). Plasma levels of factor VIII (FVIII; based on activated partial thromboplastin time) were evaluated using the Behring Coagulation System (Siemens Healthcare Diagnostics). ELI-SA test kits were used to measure thrombin-antithrombin complexes (TAT; Enzygnost TAT micro, Siemens Healthcare Diagnostics). Fibrin clot analysis Plasma fibrin clot permeability was determined as described previously. 7 The permeation coefficient (K s), which indicates the average size of pores formed in the fibrin network (with low values indicating a tightly packed fibrin structure), was calculated from the equation: K s = Q × L × η/t × A × Δp, where Q is the flow rate in time, L is the length of a fibrin gel, η is the viscosity of liquid (in poise), t is percolating time, A is the cross-sectional area (in cm 2), and Δp is a differential pressure (in dyne/cm 2).