Mechanism of action and pharmacology of unfractionated heparin.

Mechanism of Action and Pharmacology of Unfractionated Heparin Heparin is a sulfated polysaccharide with a molecular weight range of 3000 to 30 000 Da (mean, 15 000 Da). It produces its major anticoagulant effect by inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism. Heparin binds to AT through a high-affinity pentasaccharide, which is present on about a third of heparin molecules. For inhibition of thrombin, heparin must bind to both the coagulation enzyme and AT, whereas binding to the enzyme is not required for inhibition of factor Xa. Molecules of heparin with fewer than 18 saccharides lack the chain length to bridge between thrombin and AT and therefore are unable to inhibit thrombin. In contrast, very small heparin fragments containing the pentasaccharide sequence inhibit factor Xa via AT. By inactivating thrombin, heparin not only prevents fibrin formation but also inhibits thrombin-induced activation of platelets and of factors V and VIII.