HRG blocks FXII autoactivation to FXIIa, FXI activation to FXIa by FXIIa, and prekallikrein activation to plasma kallikrein by FXIIa on polyPs. All of these functions reduce thrombin formation. Alternatively, HRG, by binding to lysines on plasminogen, reduce plasmin formation such that if it were the only activity, it would contribute to thrombosis risk.