Coagulation factor X (FXa) (FXa)

The interface between the prothrombinase complex and its substrate, prothrombin, is the site of the most critical step in the blood coagulation cascade: the generation of thrombin [PubMed: 10419577]. The prothrombinase complex is composed of the serine protease coagulation factor X (FXa), the non-enzymatic cofactor factor Va (FVa), calcium ions, and a procoagulant phospholipid surface [UniProt: P00742]. This assembly is essential because FXa alone is an inefficient activator of prothrombin; however, within the prothrombinase complex, the rate of prothrombin activation is increased by approximately 300,000-fold [StatPearls: Physiology, Coagulation Cascade, 2023]. The interface involves specific binding sites (exosites) on both FXa and FVa that orient prothrombin for precise proteolytic cleavage at two sites (Arg271 and Arg320) [NCBI: PMC3117141]. This interaction is the primary target for direct oral anticoagulants (DOACs) like rivaroxaban and apixaban, which bind to the active site of FXa and prevent it from processing prothrombin [FDA: Xarelto Label]. By targeting this specific step, these drugs effectively reduce the 'thrombin burst' required for stable clot formation, making them vital for treating conditions such as deep vein thrombosis, pulmonary embolism, and stroke prevention in atrial fibrillation [PubMed: 21309526].

Other names

Factor XStuart-Prower factorFXProthrombinase complex catalytic subunitThrombokinaseProthrombinase complex interface

Direct or indirect inhibition of the serine protease activity of Factor Xa, which prevents the assembly or function of the prothrombinase complex, thereby blocking the conversion of prothrombin to thrombin.