Non-haemostatic functions of Factor Xa: Are there pleiotropic effects of the direct oral anti-Xa anticoagulants?

S. Papadaki, A.D. Tselepis



Activated Factor Xa (FXa) is a serine protease that has a key role in the coagulation cascade by converting prothrombin to thrombin, contributing to the following clot formation. Because of its role to the coagulation cascade, FXa is an important target for anticoagulant therapy emphasizing in drugs that directly inhibit its action. Apart from the role it plays in thrombosis, new evidence suggests the involvement of FXa in cellular mechanisms that mediate physiological and pathophysiological conditions, including inflammation and atherosclerosis. These non-haemostatic functions of FXa are predominantly mediated via the activation of Protease-Activated Receptors (PARs). Specifically, FXa exerts direct effects on a wide variety of cell types via activation of its two main receptors, PAR-1 and PAR-2, acting as a mediator of cellular responses that are associated with various inflammatory diseases. This review examines the non-haemostatic functions of FXa that are mediated via PARs activation, and its contribution to the pathophysiology of thromboembolic disorders. Furthermore, pleiotropic effects of rivaroxaban, a direct oral anticoagulant that targets FXa, related to atherosclerosis, inflammation and platelet activation are examined.

Keywords: Factor Xa, coagulation cascade, protease-activated receptors, anti-Xa anticoagulants