AT-independent binding to macrophages and endothelial cells also results in dose-dependent clearance. 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 the phenomenon of heparin resistance. The main limitation of heparin results from its propensity to bind to positively charged proteins and surfaces. By inactivating thrombin, heparin not only prevents fibrin formation but also inhibits thrombin-induced activation of platelets and of factors V and VIII. ![]() In contrast, very small heparin fragments containing the pentasaccharide sequence inhibit factor Xa via AT. ![]() 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. 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. Heparin binds to AT through a high-affinity pentasaccharide, which is present on about a third of heparin molecules. It produces its major anticoagulant effect by inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism. Heparin is a sulfated polysaccharide with a molecular weight range of 3000 to 30 000 Da (mean, 15 000 Da). Mechanism of Action and Pharmacology of Unfractionated Heparin Customer Service and Ordering Information. ![]()
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