Trypsin is as procoagulant as factor XIIa

To help shed light on the roles of the contact pathway of blood clotting, we quantified the relative procoagulant activities of each of the serine proteases of the clotting cascade. We added varying concentrations of the activated forms of different clotting proteases to normal human plasma and recorded the time to clot formation. We also compared these clotting activities to that of the nonspecific serine protease, trypsin. The activated proteases of the final common pathway of blood clotting exhibited relatively strong clotting activity and achieved 100-second clotting times at pM to very low nM concentrations. In contrast, factor XIIa and plasma kallikrein exhibited weak clotting activity such that it required nearly 100 nM factor XIIa to achieve a 100-second clotting time, and for plasma kallikrein this was not achieved even with 100 nM enzyme. Trypsin was slightly more procoagulant than factor XIIa. We conclude that the enzymes that trigger the contact pathway of blood clotting have remarkably weak procoagulant activity. The implications for the roles of factor XII and trypsin in thrombotic disorders and pancreatitis are discussed.