Anticoagulant therapy in general is designed to prevent either the generation or activity of thrombin; however, a cell-based model of coagulation provides a physiologic view of individual phases of the process, allowing more specific targets for attenuating the initiation, priming, or propagation of thrombus formation. Future categorization schemes will consider individual coagulation factors, individual sites on a given coagulation factor, and specific phases of coagulation to better identify an agent’s biochemical and physiologic activity. Unfractionated heparin (UFH) is a heterogeneous, negatively charged mucopolysaccharide consisting of approximately 18 to 50 saccharide units (molecular weight 5000–30,000 Da). Antithrombin (AT), required for the interaction (and subsequent neutralization) of UFH with thrombin and coagulation proteases including factors Xa, IXa, XIa, and XIIa, is bound by one third of administered drug (only molecules containing the critical pentasaccharide sequence can bind AT). Following IV administration, UFH binds to a variety of plasma proteins, endothelial cells, and macrophages, explaining, in part, the wide variability in anticoagulant effects for a given dose. It is cleared from the circulation through both a rapid saturable mechanism and a slower first-order mechanism. As a result, there is a dose-dependent half-life ranging from 60 minutes after a dose of 100 U/kg to 180 minutes for a dose of 400 U/kg (Beguin et al., 1988; Lam et al., 1976). Heparin-induced thrombocytopenia and hemorrhage are the most feared complications of UFH administration (see Chapter 29). Other adverse effects include osteopenia (with long-term administration). Low-molecular-weight heparin (LMWH) is prepared by the depolymerization of porcine UFH. A variety of processes are used, giving distinctive products whose molecular weights range from 4,000 to 6,500 Da (Hirsh and Levine, 1992). Like UFH, approximately one third of LMWH polysaccharide chains contain the pentasaccharide binding site for antithrombin. The LMWH–antithrombin complex (consisting of a predominance of shorter chain polysaccharides) has relatively weak antithrombin activity but retains the ability to inactivate factor Xa. The ratio of anti-Xa activity to anti-IIa (antithrombin) activity varies from 2:1 to 4:1. Similar to UFH, LMWH is not able to inhibit thrombin bound to fibrin (Weitz, 1997).