biostudies-literatureTucker EINHLBI NIH HHSNIH HHS689-699https://www.ebi.ac.uk/biostudies/studies/S-EPMC7046603biostudies-literatureUnknown135(9)Although thrombin is a key enzyme in the coagulation cascade and is required for both normal hemostasis and pathologic thrombogenesis, it also participates in its own negative feedback via activation of protein C, which downregulates thrombin generation by enzymatically inactivating factors Va and VIIIa. Our group and others have previously shown that thrombin's procoagulant and anticoagulant activities can be effectively disassociated to varying extents through site-directed mutagenesis. The thrombin mutant W215A/E217A (WE thrombin) has been one of the best characterized constructs with selective activity toward protein C. Although animal studies have demonstrated that WE thrombin acts as an anticoagulant through activated protein C (APC) generation, the observed limited systemic anticoagBloodThe protein C activator AB002 rapidly interrupts thrombus development in baboons.PMC7046603R01 HL049413R01 HL147821R01 HL139554R29 HL049413R44 HL095315P51 OD011092R44 HL117589Lorentz CUWood DCMcCarty OJTPelc LAGruber AMarkway BDWallisch MHinds MTShatzel JJDi Cera ETucker EIVerbout NGfalseThe protein C activator AB002 rapidly interrupts thrombus development in baboons.Although thrombin is a key enzyme in the coagulation cascade and is required for both normal hemostasis and pathologic thrombogenesis, it also participates in its own negative feedback via activation of protein C, which downregulates thrombin generation by enzymatically inactivating factors Va and VIIIa. Our group and others have previously shown that thrombin's procoagulant and anticoagulant activities can be effectively disassociated to varying extents through site-directed mutagenesis. The thrombin mutant W215A/E217A (WE thrombin) has been one of the best characterized constructs with selective activity toward protein C. Although animal studies have demonstrated that WE thrombin acts as an anticoagulant through activated protein C (APC) generation, the observed limited systemic anticoag2020-01-01T00:00:00Z2020 Feb2026-04-29T12:58:05.634Z2026-04-07T15:15:20.206ZS-EPMC70466033197700010.1182/blood.2019002771