Novel therapeutic agents in the management of hemorrhage and thrombosis

Abnormalities in the hemostatic system can lead to, on one end of the spectrum, hemorrhage, and on the opposite end, thrombosis. Over the past decade, important new agents for the management of hemorrhagic and thrombotic disorders have been developed and more are in development. The care of patients with bleeding disorders has been advanced by the development of techniques to manufacture recombinant factor products with reduced or absent exposure to human or animal proteins, prolonged half-life or with reduced immunogenicity. Though first developed for use in hemophiliacs with inhibitors, recombinant factor VIIa (rFVIIa) has now garnered experience in a variety of settings of inherited and acquired bleeding disorders. Thrombosis can occur in a variety of vascular beds and cause a spectrum of clinical sequelae. Depending on whether the thrombosis is venous or arterial, major therapeutic targets are platelets and procoagulant clotting factors. Novel targets on the platelet surface include the thrombin protease activated receptors (PAR) and the collagen receptor, glycoprotein VI (GPVI). In animal models, PAR1 and GPVI inhibition have both demonstrated a protective effect against arterial thromboembolism. For many years, the only agents available to inhibit procoagulant clotting factors were heparin and warfarin. The recent development of a pentasaccharide and other agents targeting factor Xa, factor IX, and thrombin offer useful alternatives for the management of arterial and venous thrombosis. These agents and others will be discussed in detail with respect to mechanism of action, clinical efficacy and safety.