Desmolaris, a novel factor XIa anticoagulant from the salivary gland of the vampire bat (Desmodus rotundus) inhibits inflammation and thrombosis in vivo

摘要

Blood coagulation cascade is a physiological mechanism that is triggered to avoid blood loss.Coagulation is initiated by 2 pathways that work in concert through a number of reactions of limited pro-teolysis. The extrinsic pathway is initiated by factor (F) Vila/tissue factor with formation of FXa (extrinsic Xnase) that assembles in the prothrombinase complex, resulting in activation of prothrombin to thrombin. Alternatively, the contact pathway is initiated by negatively charged molecules that activate FXII, and FXIIa cleaves and activates prekallikrein (PK). FXIIa also activates FXI, and FXIa activates FIXa. The FIXa assembles in the intrinsic Xnase complex and activates FX to FXa, leading to thrombin generation. In addition, FXI is activated by thrombin in the surface of platelets or negatively charged molecules and has emerged as an important pathway for consolidation of the clotting cascade. FXIa also plays a particularly important role in thrombus formation in vivo.