TTT by RBC-targeted fusion ATA pro-drugs. Targeted ATAs, including fibrinolytics such as PAs (tPA and uPA) and anticoagulants such as TM, bind to RBCs in the bloodstream and circulate for a prolonged time without damaging the cell carrier or causing other adverse effects typical of soluble drugs. Using RBC-targeted fusion constructs avoids the need for ex vivo loading and transfusion, thereby increasing clinical utility. Altering the mode of enzymatic activation from plasmin to thrombin enhances safety and localization. (A) scFv/uPA-T containing a variant of uPA sensitive to activation by thrombin exerts maximal fibrinolytic activity at sites of active clotting where the concentration of thrombin is greatest. (B) scFv/TM facilitates local conversion by thrombin of protein C into APC, which in turn inactivates activated coagulation factors Va and VIIIa and inhibits prothrombotic and proinflammatory signaling via protease activated receptors (PARs) on platelets and ECs, respectively.