Beyond coagulation: Coagulation protease factor VIIa in cytoprotective response

Blood coagulation, the tightly regulated biological process prevents bleeding upon injury to the blood vessels. Vessel injury exposes the sub-endothelial tissue factor (TF) to the blood stream, thereby leading to the binding of coagulation protease, factor VII/activated VII with TF, and thus initiating the extrinsic pathway of blood coagulation. Apart from coagulation, FVIIa also promotes intracellular signaling via the activation of a unique class of G-protein-coupled receptor (GPCR) family protein, protease-activated receptor 1 (PAR1), thereby promoting anti-inflammation and endothelial barrier protection. Blood coagulation and inflammation are intrinsically connected, the activation of one process often leads to the activation of the other. The present review highlights the mechanisms by which FVIIa contributes to cytoprotective responses, either by direct action or through the release of extracellular vesicles (EVs) from vascular endothelium. FVIIa, due to its well-known ability to promote coagulation, is also used as a hemostatic agent in the treatment of several hyper bleeding disorders like hemophilia, thrombocytopenia etc. In addition to its hemostatic role, the topics discussed in the present review open a new therapeutic off-label effect of FVIIa, i.e., providing anti-inflammatory and vascular protective responses in several bleeding disorders and beyond.