Activation of Hageman Factor by Factor XIA-HMW Kininogen

Abstract

Plasma deficient in prekallikrein possesses an abnormality in the kinetics of surface dependent initiation of coagulation and fibrinolysis. This defect appears to be secondary to a diminished rate of Hageman factor activation, however the abnormality is progressively diminished as the time of incubation of the plasma with appropriate surfaces is increased. Since factor XI and prekallikrein circulate bound to HMW kininogen and HMW kininogen is known to augment the activation of factor XI and prekallikrein by activated Hageman factor, the ability of factor XIA to activate Hageman factor was examined. One ug Hageman factor was bound to supercel alone, or in the presence of 1.5 ug HMW kininogen and 0.1 to 1.0 ug factor XIA for varying time periods (0–60 min). The pellet was washed X 3 and bound activated Hageman factor was assayed by its ability to convert prekallikrein to kallikrein. The kallikrein generated was quantified by release of p-nitroaniline from α-benzoyl phe-val-arg-p-nitroanilide. Factor XIA alone was a weak activator of Hageman factor and the quantity of kallikrein generated was augmented when HMW kininogen was included in the incubation mixture. With limited HMW kininogen the Hageman factor activity appeared proportional to the factor XIA added. The same result was obtained with factor XIA isolated from prekallikrein deficient plasma. The data suggest that factor XIA plus HMW kininogen may represent one of the additional feedback mechanisms by which Hageman factor may be activated and thereby contribute to the gradual activation observed in prekallikrein deficient plasma.