Low-Molecular-Weight Heparins in the Treatment of Venous Thromboembolism

For many decades, the conventional wisdom has been that patients with a diagnosis of acute venous thromboembolic disease confirmed by objective techniques should receive an initial continuous intravenous course of unfractionated heparin for at least 5 days to prevent early and late recurrences [1, 2]. Oral anticoagulant therapy can be started simultaneously and should be continued for at least 3 months [3]. Because the pharmacokinetic response of unfractionated heparin is unpredictable, daily laboratory monitoring and dose adjustments are required; therefore, hospital admission for treatment of acute thromboembolic disease is usually unavoidable [4].

This standard practice is now being challenged by the development of low-molecular-weight heparins, which are manufactured by depolymerization of unfractionated heparin. The concept behind the development of these refined compounds is that inhibition of activated coagulation factor X (Xa) is crucial for the antithrombotic activity of heparins. Unlike unfractionated heparin, which has equivalent activity against both factor Xa and thrombin, low-molecular-weight heparins have greater activity against factor Xa. Therefore, it is expected that low-molecular-weight heparins will be associated with anti-thrombotic activity at least equal to that of unfractionated heparin, whereas the risk for hemorrhage is smaller. However, the most important advantages of low-molecular-weight heparins are their superior pharmacokinetic properties. Compared with unfractionated heparin, they bind less to plasma proteins, blood cells, and the endothelium, resulting in nearly complete bioavailability, …