Consequently, an alternative anticoagulant should be considered in patients with HIT who have previously been treated with hirudin. Bivalirudin A 20-amino acid synthetic polypeptide, bivalirudin is an analog of hirudin.218 The amino terminal D-Phe- Pro-Arg-Pro sequence, which binds to the active site of thrombin, is connected via four Gly residues to a carboxy-terminal dodecapeptide that interacts with exosite 1 on thrombin.219 Like hirudin, bivalirudin forms a 1:1 stoichiometric complex with thrombin. However, once bound, thrombin cleaves the Pro-Arg bond within the amino terminal of bivalirudin, thereby allowing recovery of thrombin activity.220 Bivalirudin has a plasma half-life of 25 min after IV injection,221 and only 20% is excreted via the Bivalirudin is licensed as an alternative to hep- arin in patients undergoing percutaneous interven- tions for unstable angina or non-ST-elevation or ST-elevation myocardial infarction and in patients with HIT (with or without thrombosis) who require per- cutaneous coronary interventions.223 The currently recommended dose is a bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the duration of the procedure. Dose reduction should be considered in patients with moderate to severe renal impairment. The drug has also been explored as an alternative to heparin in patients undergoing cardiopulmonary bypass surgery. In contrast to hirudin, bivalirudin is not immunogenic. However, antibodies against hiru- din can cross-react with bivalirudin in vitro. The clinical consequences of this cross-reactivity are uncertain. Argatroban Argatroban is a small molecule competitive inhib- itor of thrombin (molecular weight, 500 kDa). It HIT from danaparoid to vitamin K antagonists. The long half-life of danaparoid is a disadvantage if patients require urgent surgery or invasive procedures. It also is problematic if patients have serious bleeding because there is no antidote for danaparoid. 