Future prospects of prophylaxis for deep vein thrombosis.

The last decade has witnessed substantial progress in the prevention and treatment of venous thromboembolism. However, the risk of deep vein thrombosis remains high in trauma patients and those undergoing orthopaedic surgery despite use of the best available prophylaxis. Existing antithrombotics also carry a significant risk of bleeding and other adverse effects, including heparin-induced thrombocytopenia (HIT). More effective and safer anticoagulants are therefore needed. Current approaches for improving the benefit:risk ratio of antithrombotic therapy include the development of indirect thrombin inhibitors with a high anti-Xa:anti-IIa activity ratio, and the use of direct thrombin inhibitors. Novel indirect thrombin inhibitors under investigation include pentasaccharide and the heparinoid danaparoid. These agents may offer reduced bleeding risk compared with conventional therapies, but there is no evidence of greater antithrombotic efficacy. However, due to low cross-reactivity with anti-heparin-platelet factor 4 antibodies, danaparoid and pentasaccharide may prove valuable in the management of HIT. Theoretically, the antithrombotic effect of direct thrombin inhibitors may be greater than that of indirect inhibitors because direct inhibitors are not dependent on endogenous cofactors and are able to inhibit both free and clot-bound thrombin. Direct inhibitors of the active site of thrombin and recombinant variants of hirudin, originally derived from the medicinal leech, are currently under investigation. Early data on lepirudin and desirudin suggest that recombinant hirudins may have clinical applications in thromboprophylaxis for high-risk patients, acute cardiology indications and HIT.