Strategies for ATA targeting. The action of clot-targeted scFv/ATA has been studied in animal models of arterial and venous thrombosis. ATA fusions or antibody conjugates injected in the vasculature shortly after thrombotic occlusion (T3) circulate for a limited period of time. Affinity to clot components enhances the fraction of injected ATA accumulating at the thrombotic site. (A-B) Fibrin-targeted ATAs bind to fibrin accessible at the clot surface and to additional fibrin depositing at the site of thrombosis in the course of clot growth and remodeling (light gray area surrounded by dash line). (C) ATAs bind to activated platelets accessible from the clot surface and in the remodeling clot, or to resting platelets (which may prolong circulation and provide continuous platelet-mediated delivery into secondary or remodeling clots). (A) Clot-associated anticoagulants (eg, hirudin) inhibit additional formation of thrombin, thus limiting thrombus growth, (B-C) whereas PAs facilitate dissolution of clots and foster reperfusion.