Heparin Binds Plasma Proteins Angiomax Bivalirudin Binds Specifically

Heparin Binds Plasma Proteins: Angiomax® (Bivalirudin) Binds Specifically to Thrombin Heparin (long strand) binds to other plasma proteins (colored molecules) and platelets, reducing heparin’s availability to bind to AT. Heparin-binding proteins are elevated in acute coronary syndrome (ACS). Hirsh J et al. Chest. 2001; 119(1 suppl): 64 S-94 S. Angiomax (bright blue) binds only to thrombin (orange). Angiomax is not neutralized by other plasma proteins or platelets; it remains fully active near thrombus. Weitz JI et al. Thromb Res. 2002; 106: V 275 -V 284. Wittkowsky AK. Pharmacother. 2002; 22(6 Pt 2): 97 S-104 S.

Consequences of Nonspecific Binding Heparin is neutralized by platelet factor 4, (PF 4), which is present in high concentrations near vascular injury. Angiomax® (bivalirudin) does not bind to PF 4, and remains fully active. Thrombin continues activating platelets. There is no risk of HIT/TS or other thrombotic events associated with PF 4/heparin antibodies. PF 4/heparin complex antibodies activate platelets, causing thrombocytopenia as well as heparin-induced thrombocytopenia thrombosis syndrome (HIT/TS). Weitz JI et al. Thromb Res. 2002; 106: V 275 -V 284. Williams RT et al. Circulation. 2003; 107: 2307 -2312. Weitz JI et al. Thromb Res. 2002; 106: V 275 -V 284.

Heparin Increases Platelet Activation Heparin makes platelets more reactive to activation by other agonists, such as adenosine diphosphate (ADP). Heparin binds to the platelet GP IIb/IIIa receptor. Given the various ways heparin increases platelet activation, its use may actually increase the need for antiplatelet agents. Becker R et al. J Invasive Cardiol. 2003; (suppl): 1 -15. Sobel M et al. J Vasc Surg. 2001; 33: 587 -594. Xiao Z et al. Circulation. 1998; 97: 251 -256.

Heparin Has a Direct Effect on Platelets • Heparin increases platelet activation in unstable angina patients Maximum Aggregation (%) 20 P<0. 001 15 Pre-heparin Heparin 10 5 0 ADP (0. 3125 µM) TRAP (0. 625 µM) TRAP=thrombin receptor agonist peptide. Reproduced with permission of Xiao Z et al. Circulation. 1998; 97: 253.

Angiomax® (Bivalirudin) Significantly Decreases Platelet Reactivity Platelet reactivity in response to 1 μM ADP P=0. 01 P<0. 0001 Percentage 45 40 42% Fibrin binding 38% P-selectin expression 34% 35 34% 30 25 UFH Aggarwal A et al. J Thrombolysis. 2002; 13: 161 -165. Angiomax