Pharmacological prevention of venous thromboembolism in medical patients at risk.

Acutely ill general medical patients are at moderate-to-high risk of venous thromboembolism (VTE); approximately 10-30% may develop deep vein thrombosis or pulmonary embolism, the latter being a leading contributor to deaths in hospital. Medical conditions associated with a high risk of VTE include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, and infectious disease. Predisposing risk factors for VTE in medical patients include history of VTE, history of malignancy, complicating infections, increasing age, thrombophilia, prolonged immobility, and obesity. Unfractionated heparin (UFH), low-molecular weight heparin (LMWH), and fondaparinux sodium have been shown to be effective agents in the prevention of VTE in medical patients. In this setting, UFH has a higher rate of bleeding complications than LMWH. There is no evidence supporting the use of aspirin, warfarin, or mechanical methods to prevent VTE in medical patients. We recommend either LMWH or fondaparinux sodium as well tolerated and effective thromboprophylactic agents in medical patients.

New antithrombotics in the prevention of thromboembolic disease.

New anticoagulants are under development to improve on current ones that, although effective, have limitations in efficacy, safety and convenience. We have reviewed the use of these agents as thromboprophylactic drugs. These new agents have more specific modes of action and can be divided into three groups. Inhibitors of the initiation of coagulation work via inhibition of the factor VIIa/tissue factor complex. Inhibitors of propagation of coagulation include parenteral and oral factor Xa inhibitors, factor IXa inhibitors, inhibitors of factor Va and VIIIa, activated Protein C, soluble thrombomodulin and SNAC-Heparin. Finally, direct inhibitors of thrombin are under development both for parenteral and oral administration. Several new drugs, such as fondaparinux, hirudin, argatroban, bivalirudin and ximelagatran, have already been licensed for specific indications and are being investigated for more general usage. Other drugs reviewed are in much earlier stages of development.