Factor Xa (FXa) is a key
enzyme that is positioned at the convergence of the intrinsic and extrinsic pathways in the blood coagulation cascade, and inactivation by a specific FXa inhibitor effectively prevents the generation of
thrombin. Various types of low molecular weight (LMW)
heparin, which function as semi-selective and indirect FXa inhibitors, are replacing
unfractionated heparin (UFH) as agents for the prevention and treatment of
venous thromboembolism (VTE), as well as in initial treatment for coronary events. Of those,
heparinoid has been shown to be safer and more effective for the prevention of postoperative VTE than UFH, especially for treatment of
heparin-induced
thrombocytopenia (HIT). Further, synthetic pentasaccharide has been found to offer advantages over current thromboprophylactic regimens in a number of patients undergoing major
orthopedic surgery. Other studies have shown that pentasaccharide is more effective for overall VTE in comparison with LMW
heparin, though it was also associated with an increased rate of major
bleeding. Synthetic, selective, and direct inhibitors to FXa, such as
DX-9065a, are highly potent and orally bioavailable
antithrombotic agents that have demonstrated an improved side effect profile, probably by allowing sufficient
thrombin to remain for platelet activation and normal hemostasis, while preventing pathological
thrombus formation. For
thrombosis therapy, the most desirable type of
antithrombotic agent is an orally active
drug that has a broad range of effective doses and no hemorrhagic side effects. Presently, many types of direct inhibitors are in various stages of clinical trials and expected to provide significant benefits as compared to currently utilized
therapy strategies.