Effect of ISIS 2302 on fibrinogen clotting in a purified thrombin time assay. Purified recombinant wild-type thrombin (•), thrombin R70E (exosite I mutant) (○), or thrombin R89E (exosite II mutant) (▪) was added to clotting buffer (see Materials and Methods) containing increasing amounts of ISIS 2302 (200 μL). The assay was initiated by addition of 50 μL of 2 mg/mL human fibrinogen and the time to clot formation determined. Clotting times are expressed as the mean of triplicate determinations with error bars representing ±2 SD.