Anticoagulation in the Prevention and Treatment of Pulmonary Embolism

Abstract

The anticoagulant agents commonly used in prevention and treatment of pulmonary embolism are unfractionated heparin, and more recently, low molecular weight heparins, and oral anticoagulants. Unfractionated heparin is the drug of choice for prophylaxis and short-term treatment of pulmonary embolism. Oral anticoagulants are used for prophylaxis in high risk patients and in long-term treatment of pulmonary embolism. Independent overview analysis of clinical trials in elective surgery showed a 60 to 70% reduction in the incidence of fatal pulmonary embolism in heparin-treated patients when they were compared with placebo-treated patients. Low dose heparin has also been shown to be effective in reducing venous thromboembolism after myocardial infarction and other serious medical disorders. In high risk patients prophylaxis with low molecular weight heparins or adjusted doses of unfractionated heparin is recommended. The objectives of treating patients with pulmonary embolism are to prevent death, to reduce morbidity from the acute event, and to prevent thromboembolic pulmonary hypertension. These objectives are achieved by the administration of heparin followed by oral anticoagulants. Heparin is generally administered for 7 to 10 days and is followed by oral anticoagulants. Although widely used and effective in the prevention and treatment of pulmonary embolism, unfractionated heparin has some pharmacological limitations. Heparin presents an aspecific "nonfunctional" binding to plasma proteins such as fibrinogen, factor VIII, vitronectin, and fibronectin. This aspecific binding limits the anticoagulant effect of unfractionated heparin and, is responsible for the heparin resistance observed in some patients with pulmonary embolism as well as of the high intersubject variability of the heparin-induced anticoagulant effect. Antithrombotic agents, such as low molecular weight heparins and pure thrombin inhibitors (hirudin and its analogues), do not specifically bind to plasma protein and they will probably improve the efficacy and practicality of the treatment of pulmonary embolism.