5 Heparin and low-molecular-weight heparin in the treatment of venous thromboembolism

Venous thromboembolism (deep vein thrombosis and pulmonary embolism) continues to constitute a major clinical challenge. Effective and safe prophylactic measures against venous thromboembolism are now available for most high risk patients. In spite of this, pulmonary embolism is responsible for approximately 150 000 to 200 000 deaths per year in the United States alone. Over the past 20 years, based on a number of high quality (Level I) clinical trials, patterns of practice with respect to the treatment of venous thromboembolism have changed dramatically. The standard treatment of venous thromboembolism has been the use of unfractionated heparin by continuous intravenous infusion, with laboratory monitoring using the activated partial thromboplastin time (APTT), with warfarin starting on day 1 or 2 and continued for 3 months. Unfractionated heparin has withstood the test of time and has been shown to be safe and effective in preventing recurrent venous thromboembolism and death in numerous clinical trials. The response of individual patients to heparin is highly variable, requiring frequent laboratory monitoring. Heparin has a number of other troublesome side effects including bleeding, heparin-induced thrombocytopenia and osteoporosis. The low-molecular-weight heparins have a number of advantages over unfractionated heparin. In particular, their increased bioavailability and prolonged half-life permit once daily subcutaneous injections and their predictable antithrombotic response based on body weight permits treatment without laboratory monitoring. Low-molecular-weight heparin in therapeutic doses causes less bleeding than unfractionated heparin and evidence is accumulating that the incidence of heparin-induced thrombocytopenia and osteoporosis are decreased as well. In individual clinical trials and meta-analyses, low-molecular-weight heparin treatment results in decreased recurrent thromboembolism, major bleeding and death when compared with unfractionated heparin in the treatment of deep vein thrombosis and pulmonary embolism. These agents have also been shown to be both effective and safe for the out-of-hospital treatment of venous thrombosis. Therefore, in many countries, low-molecular-weight heparin has replaced unfractionated heparin for the treatment of venous thromboembolism.