Indirect vs Direct Thrombin Inhibition Indirect inhibition by heparin requires the presence of antithrombin (AT), the actual inhibitor. Heparin (long yellow strand) binds to AT, causing a shape change that increases the ability of AT to inhibit thrombin. Direct inhibition with Angiomax® (bivalirudin) inhibits thrombin directly with high affinity and specificity. It requires no cofactor, and acts alone. Bivalirudin’s effectiveness is not affected by variability in the concentration of a co-factor like AT. Key Message: Angiomax inhibits thrombin directly; therefore, it does not promote coagulation. On the left panel, heparin is not labeled but is represented by the long strand. Several “antithrombin” agents have been developed to prevent coagulation for many clinical circumstances. Heparin is a ubiquitous agent in the hospital and outpatient settings that is an imprecise and inefficient anticlotting agent. Indirect inhibition by heparin requires the presence of antithrombin (AT), the actual inhibitor in the clotting cascade. The panel on the left shows heparin (see the long strand) binding to AT and causing a shape change that increases the ability of AT to inhibit thrombin. Angiomax inhibits thrombin directly with high affinity and specificity. The panel on the right shows Angiomax binding to thrombin. Angiomax provides rapid, effective thrombin inhibition to prevent thrombosis and platelet effects. Hirsh J et al. Chest. 2001;119(1 suppl):64S-94S. Weitz JI et al. Thromb Res. 2002;106:V275-V284. Gibson CM, 2006