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  • Title: Heparin: from animal organ extract to designer drug.
    Author: Middeldorp S.
    Journal: Thromb Res; 2008; 122(6):753-62. PubMed ID: 17996279.
    Abstract:
    Anticoagulant therapy with heparin has been the cornerstone of treatment and prevention of thrombosis for many decades. The properties and indications of heparin, as well as the development of its derivates, the low-molecular-weight heparins, and ultimately the synthetically designed pentasaccharides, are reviewed from a clinical perspective. Unfractionated heparin is a heterogeneous mixture of polysaccharides and glycosaminoglycuronsulfate which for commercial preparations is generally extracted from bovine and sheep lungs and porcine intestinal mucosa. Low-molecular-weight heparins are fragments of unfractionated heparin produced by controlled enzymatic or chemical depolymerization processes with the main difference being in their relative inhibitory activity against factor Xa and thrombin. Pentasaccharides are synthetic drugs that accelerate the interaction between factor Xa and antithrombin but selectively inhibit factor Xa activity. Many clinical studies in the prevention and treatment of venous thromboembolism in several patient groups, as well as for arterial indications have been performed over the last decades. Low-molecular-weight heparins have proved to be more efficacious and safer than unfractionated heparin. Phase 3 trials have demonstrated similar or superior efficacy combined with superior safety for the short-acting pentasaccharide fondaparinux, as compared to low-molecular-weight heparin. Results of phase 3 trials of the long-acting pentasaccharide idraparinux which is being compared to vitamin K antagonists for long-term treatment are much awaited.
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