Bivalirudin, a 20 amino acid polypeptide, is a synthetic analog of hirudin. Like the hirudins it is also a bivalent DTI. It has an amino-terminal D-Phe-Pro-Arg-Pro domain that is linked via four Gly residues to a dodecapeptide analog of the carboxy-terminal of hirudin. The amino-terminal domain binds to the active site and the carboxy-terminal domain binds to exosite 1 on thrombin. Different from the hirudins, once bound thrombin cleaves the Arg-Pro bond at the amino-terminal of bivalirudin and as a result restores the functions to the active site of the enzyme.  Even though the carboxy-terminal domain of bivalirudin is still bound to exosite 1 on thrombin, the affinity of the bond is decreased after the amino-terminal is released.  This allows substrates to substrates to compete with cleaved bivalirudin for access to exosite 1 on thrombin. The use of bivalirudin has mostly been studied in the setting of acute coronary syndrome. A few studies indicate that bivalirudin is non-inferior compared to heparin and that bivalirudin is associated with a lower rate of bleeding. Unlike the hirudins, bivalirudin is only partially (about 20%) excreted by the kidneys, other sites such as hepatic metabolism and proteolysis also contribute to its metabolism, making it safer to use in patients with renal impairment; however, dose adjustments are needed in severe renal impairment.