Limitations of established antithrombotic strategies

The incidence of venous thromboembolism has declined in recent years, probably due to the successful use of prophylactic strategies. However, pulmonary embolism remains the most common preventable cause of hospital death in industrialized countries. A number of clinical studies have shown that when used appropriately current antithrombotic therapies, such as unfractionated heparin, oral anticoagulants and low-molecular-weight heparins, are effective in preventing thromboembolic events in the majority of patients. However, surveillance data indicate that in certain high-risk clinical settings a significant proportion of patients still develop deep vein thrombosis despite use of the most effective prophylaxis methods currently available. Currently available antithrombotic therapies are also associated with a risk of treatment-specific adverse effects and various practical limitations which restrict their clinical benefit and influence cost-effectiveness. Risk of bleeding, heparin-induced thrombocytopenia, and drug interactions are the most important safety concerns. The need for inconvenient and costly dose adjustment and laboratory monitoring, intravenous or subcutaneous administration, and restrictions on methods of anaesthesia are key practical drawbacks. This paper reviews clinical and practical aspects of existing therapeutic options and develops a profile for the ideal thromboprophylactic agent. The direction of current research into the development of improved prophylactic modalities designed to overcome existing limitations is briefly discussed.