Apixaban, an oral direct factor Xa inhibitor, inhibits human clot-bound factor Xa activity in vitro

• References

• 1 Eisenberg PR, Siegel JE, Abendschein DR. et al. Importance of factor Xa in determining the procoagulant activity of whole-blood clots. J Clin Invest 1993; 91: 1877-1883.
• 2 Hérault JP, Bernat A, Pflieger AM. et al. Comparative effects of two direct and indirect factor Xa inhibitors on free and clot-bound prothrombinase. J Pharmacol Exp Ther 1997; 283: 16-22.
• 3 Meddahi S, Bara L, Fessi H. et al. Determination of prothombinase activation after adding human purified prothrombin to human clot: comparison of hirudin, an activated factor II inhibitor, with DX9065a, an activated factor X inhibitor, on clot-associated thrombin and on prothrombin activation. Blood Coagul Fibrinolysis 2005; 16: 125-133.
• 4 Weitz JI, Hudoba M, Massel D. et al. Clot-bound thrombin is protected from inhibition by heparin-anti-thrombin III but is susceptible to inactivation by anti-thrombin III-independent inhibitors. J Clin Invest 1990; 86: 385-391.
• 5 Sinha U, Lin PH, Edwards ST. et al. Inhibition of purified factor Xa amidolytic activity may not be predictive of inhibition of in vivo thrombosis: implications for identification of therapeutically active inhibitors. Arterioscler Thromb Vasc Biol 2003; 23: 1098-1104.
• 6 Pinto DJ, Orwat MJ, Koch S. et al. Discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa. J Med Chem 2007; 50: 5339-5356.
• 7 Wong PC, Crain EJ, Xin B. et al. Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies. J Thromb Haemost 2008; 6: 820-829.
• 8 Wong PC, Watson CA, Crain EJ. Arterial antithrombotic and bleeding time effects of apixaban, a direct factor Xa inhibitor, in combination with antiplatelet therapy in rabbits. J Thromb Haemost 2008; 6: 1736-1741.
• 9 Lassen MR, Davidson BL, Gallus A. et al. The efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement. J Thromb Haemost 2007; 5: 2368-2375.
• 10 Büller H, Deitchman D, Prins M. et al. Efficacy and safety of the oral direct factor Xa inhibitor apixaban for symptomatic deep-vein thrombosis. The Botticelli DVT dose-ranging study. J Thromb Haemost 2008; 6: 1313-1318.
• 11 Mann KG. Biochemistry and physiology of blood coagulation. Thromb Haemost 1999; 82: 165-174.
• 12 Hogg PJ, Jackson CM. Fibrin monomer protects thrombin from inactivation by heparin-antithrombin III: implications for heparin efficacy. Proc Natl Acad Sci USA 1989; 86: 3619-3623.
• 13 McKenzie CR, Abendschein DR, Eisenberg PR. Sustained inhibition of whole-blood clot procoagulant activity by inhibition of thrombus-associated factor Xa. Arterioscler Thromb Vasc Biol 1996; 16: 1285-1291.
• 14 Kotzé HF, Lamprecht S, Badenhorst PN. et al. Transient interruption of arterial thrombosis by inhibition of factor Xa results in long-term antithrombotic effects in baboons. Thromb Haemost 1997; 77: 1137-1142.
• 15 Depasse F, Busson J, Mnich J. et al. Effect of BAY 59–7939 – a novel, oral, direct factor Xa inhibitor – on clot-bound factor Xa activity in vitro. J Thromb Haemost. 2005 3. (Suppl 1): Abstract P1104.
• 16 Wong PC, Crain EJ, Pinto DJ. et al. Dose-dependent antithrombotic effects of apixaban, an oral direct factor Xa inhibitor, in prevention and treatment of thrombosis in rabbit models of arteriovenous-shunt and venous thrombosis at doses that preserve hemostasis. Blood (ASH Annual Meeting Abstracts). 2007 110: Abstract 933.