Heparin and other rapidly acting anticoagulants

Unfractionated heparin, derived from porcine intestine, is the prototype of a rapidly acting anticoagulant. It has been used for over 60 years to arrest or prevent thrombus growth. Low-molecular-weight heparins, available in the last 20 years, are manufactured from unfractionated heparin and have superior dose-response relationships because of fewer nonspecific reactions with plasma proteins and cells. Fondaparinux is a recently approved five-saccharide synthetic molecule that carries the evolution of heparin further. It is a pure Xa inhibitor, with minimal nonspecific interactions. It does not appear to elicit the antibody that leads to heparin-induced thrombocytopenia (HIT). All of these agents are given either intravenously or subcutaneously. They act indirectly by activating the natural plasma inhibitor, antithrombin III. Direct thrombin inhibitors bind directly to thrombin's active site without interaction with the cofactor, antithrombin III. Lepirudin (Refludan; Berlex, Wayne, NJ) and argatroban (Argatroban; GlaxoSmithKline, Research Triangle Park, NC) are given intravenously and are usually used in HIT and thrombosis associated with HIT. Bivalirudin (Angiomax; The Medicines Company, Parsippany, NJ) is a parenteral direct thrombin used in place of heparin in percutaneous coronary interventions. Ximelagatran (Exanta; AstraZeneca, Wilmington, DE) is an oral direct thrombin inhibitor under development for both acute and chronic anticoagulation.