CONTEXT: C1 inhibitor (C1-INH) is an alpha2-globulin that blocks esterolytic activity of the first component of the classic complement cascade. The alpha-granules of normal human platelets also contain C1-INH, which is expressed on the platelet surface during platelet secretion in healthy patients, but it is clearly reduced in patients with hereditary angioedema (HAE).
OBJECTIVE: To evaluate the effects of in vivo C1-INH concentrate infusion on platelet responsiveness and coagulation system activity in patients with HAE. DESIGN: Assessment of the platelet activity and plasma levels of C1-INH, activated factor XII (XIIa), and prothrombin fragment F1.2 (F1.2) before and after infusion of 15 U/kg of C1-INH concentrate.
PATIENTS: In 6 patients (4 men and 2 women), HAE was diagnosed according to the accepted clinical and laboratory criteria.
MEASUREMENTS: Platelet aggregation (final concentrations: adenosine diphosphate, 0.5, 1.25, and 2.5 microM; collagen, 5 microg/mL), C1-INH antigen (radial immunodiffusion), C1-INH activity (chromogenic substrates), and XIIa and F1.2 (enzyme-linked immunosorbent assay).
RESULTS: After C1-INH infusion, we observed a prompt increase of C1-INH level and a slow return toward its plasma preinfusion values within 4 to 7 days, a significant decrease of both adenosine diphosphate- and collagen-induced platelet aggregation versus preinfusion values (maximum after 1-2 days; P <.001), and a rapid decrease of high basal values of XIIa and F1.2 in 30 and 120 minutes, respectively.
CONCLUSIONS: These data show a role of C1-INH in the control of platelet activity and that its deficiency increases platelet aggregability and plasma levels of XIIa and F1.2 in patients with HAE.