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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1094.)
© 2001 American Heart Association, Inc.

Editorial

Mechanism of Action and Pharmacology of Unfractionated Heparin

Jack Hirsh; Sonia S. Anand; Jonathan L. Halperin; Valentin Fuster

Correspondence to Jack Hirsh, MD, Hamilton Civic Hospitals Research Center, Henderson General Division, 711 Concessions St, Hamilton, Ontario L8V 1C3, Canada. E-mail Jhirsh@thrombosis.hhscr.org

Key Words: AHA Scientific Statement anticoagulants heparin

An updated statement by the American Heart Association (AHA) on the pharmacology and clinical use of heparin and low-molecular-weight heparin (LMWH) is published online at http://www.atvb.org and also appears in the June 19, 2001 issue of Circulation. The following is a summary of the AHA statement. We have not cited references; these can be accessed from the full text.

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.

The main limitation of heparin results from its propensity to bind to positively charged proteins and surfaces. Pharmacokinetic limitations are caused by AT-independent binding of heparin to plasma proteins, proteins released from platelets, and endothelial cells, resulting in a variable anticoagulant response and . . . [Full Text of this Article]

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