The Kinin System of Human Plasma V. The Probable Derivation of Prekallikrein Activator from Activated Hageman Factor (XIIa)

Partial Purification of Plasma Thromboplastin Antecedent (Factor XI) and its Activation by Trypsin

“…The clotpromoting activity of the Hageman factor preparation evolved upon contact with glass decayed during its incubation with trypsin, a result consistent with that reported by Soltay, Movat, and Ozge-Anwar (24). These data suggest that clot-promoting activity was evolved from PTA by trypsin enzymatically and that this PTA activation was not via Hageman factor activation.…”

“…These results also exclude the possibility that the preparation of trypsin used for PTA activation could have been contaminated with Hageman factor which might activate PTA. Several groups of investigators have reported that a low molecular weight (30.-000-40,000 D) anionic substance (prealbumin or prekallikrein activator) can be derived from Hageman factor through treatment with plasmin or trypsin (24,27,28). This substance activates prekallikrein but has only about 1/50th the clot-promoting activity compared with the parent Hageman factor.…”

Purification of High Molecular Weight Kininogen and the Role of This Agent in Blood Coagulation

“…HF-fragments (approximate mol wt 30,000) are derived from HF (mol wt 80,000) by the action of proteolytic enzymes such as plasmin, kallikrein, or trypsin (25)(26)(27). These fragments are very potent activators of prekallikrein, but only weakly clot-promoting (28).…”

Fletcher factor deficiency. A diminished rate of Hageman factor activation caused by absence of prekallikrein with abnormalities of coagulation, fibrinolysis, chemotactic activity, and kinin generation.

“…The ability of intact activated Hageman factor to reconstitute the coagulation, fibrinolytic, and chemotactic defects of Fletcher factor-deficient plasma suggests that prekallikrein affects these functions by accelerating the conversion of unactivated Hageman factor to activated Hageman factor (20). However, activated Hageman factor or its fragments convert prekallikrein to kallikrein (9,14,21,22 (8). Since prekallikrein corrected both the coagulation and fibrinolytic defects of Fletcher factor-deficient plasma, it appeared likely that prekallikrein was acting at Hageman factor, the only protein known to be common to both pathways.…”