Unfractionated Heparin and Other Antithrombin Mediated Anticoagulants

Extract

Several anticoagulants work by enhancing the role of antithrombin (previously called antithrombin III). The group includes one of the oldest anticoagulants, unfractionated heparin (UFH), along with the more recent low-molecular-weight heparins (LMWH), heparinoids, i.e., Danaparoid® that has been removed from the market, and the synthetic drugs fondaparinux and idraparinux, currently in clinical trials. All of these agents work indirectly to inhibit the generation of thrombin and fibrin. They work by binding to antithrombin, creating a marked increase in the affinity of antithrombin for the serine protease active site of the coagulation factor(s) to inhibit their activity. While these drugs share this mechanism of action, the drugs differ in the coagulation factors most targeted for inactivation. Moreover, they differ in their pharmacologic properties leading to significant differences with regard to predictability and flexibility of dosing and administration, as well as toxicity profiles (Table 1).