Protein anticoagulants targeting factor VIIa-tissue factor complex: a comprehensive review.

Anticoagulants are pivotal for the treatment of debilitating thromboembolic and associated disorders. Current anticoagulants such as heparin and warfarin are non-specific and have a narrow therapeutic window. These limitations have provided the impetus to develop new anticoagulant therapies/strategies that target specific factors in the blood coagulation cascade, ideally those located upstream in the clotting process. Factor VIIa (FVIIa) presents an attractive target as it, in complex with tissue factor (TF), acts as the prima ballerina for the formation of blood clot. A comprehensive review delineating the structure-activity relationship of protein/peptide anticoagulants targeting FVIIa or TF-FVIIa complex is absent in the literature. In this article, we have addressed this deficit by appraising the peptide/protein anticoagulants that target FVIIa/TF-FVIIa complex. Further, the current status of these anticoagulants, with regard to their performance in different clinical trials has also been presented. Lastly, the unexplored domains of these unique proteins have also been highlighted, which will facilitate further translational research in this paradigm, to improve strategies to counter and treat thromboembolic disorders.