1. Anti-Thrombotic Review
Mid-Year Sales Meeting
Bloomington, IN
July 13th – 17th

2. Objectives
Review of Hexabrix Anti-thrombotic & Anti-platelet Properties
Overview of Other Anti-Thrombotic Therapies used in the Cath Lab
Why is this important??

3. Anti-Thrombotic Review
So what happens?

4. Anti-Thrombotic Review
Blood Vessel
Endothelium
Subendothelium
INJURY
Collagen
VWF
Tissue Factor
Vaso-
constriction
Platelet Adhesion
& Secretion
Coagulation Cascade
Thrombin
Platelet aggregation
Fibrin
Haemostatic plug
Dr Isobel Ford

5. Anti-Thrombotic Review
So what role does Hexabrix play? 2 3 1 4

6. Anti-Thrombotic Review
So what role does Hexabrix play? 1
Hexabrix, does not activate resting platelets, unlike nonionic monomers.
Doesn’t direct platelets to change shape, release pro-coagulant mediators or to adhere to anything.
This prevents/delays formation of the platelet clot. 2
Hexabrix binds w/ Thrombin, preventing it from activating platelets; therefore preventing/delaying the formation of the platelet plug. 3
Hexabrix inhibits the generation of thrombin, reducing the amount of thrombin in the system; therefore
Hexabrix inhibits the formation of fibrin. 4
These two together prevents/delays the formation of the fibrin mesh.

7. Anti-Thrombotic Review
So, which studies support these properties?
(in vitro & animal) 1
Resting Platelet Activation
S Heptinstall et al. British Journal of Heamtology. 1998
N Chronos et al. Circulation. 1993
L Melton et al. Acad Rad.1995
JM Idee & C Corot. Fundam Clin Pharmacol. 1999 2
Inhibition of Thrombin and Fibrin
Li and Gabriel. Acad Rad. 1997
JJ Ing et al. Radiology
PM Kopko et al. Radiology. 1990
J Fareed et al. Radiology. 1990
C Corot et al. Blood Coag and Fibrinolysis. 1996
R Al Dieri et al. Journal of Thrombosis and Hemostasis. 2003
CP Markou et al. Thrombo and Heamost 3 4

8. Anti-Thrombotic Review
So, the anti-platelet properties support the better clinical profile of Hx. (Clinical)
Le Feuvre et al. Cathet Cardiovasc Interv. 2006
CL Grines et al. JACC

9. Anti-Thrombotic Review
What about all of the other therapies used in the Cath Lab?

10. Anti-Thrombotic Review
Four types of Anti-Thrombotics
Anti-Platelet
Anti-coagulant
Thrombolytic
Non-Medicinal

11. Anti-Thrombotic Review
Anti-Thrombotics
Anti-Platelet
Decrease Platelet Aggregation & Inhibit Thrombus Formation Effective in arterial circulation
Gp IIb/IIIa Inhibitors
Abciximab (ReoPro), Eptifibatide (Integrilin)
ADP Receptor Inhibitors
Clopidigrel (Plavix), Prasugrel (Effient)
Prostglandin Receptor Inhibitors
Prostacyclin, Treprostinil (Remodulin)
COX Inhibitors
Acetylsalicyclic Acid/Aspirin
No Platelet Activation
Ioxaglate (Hexabrix)

12. Anti-Thrombotic Review
Anti-Thrombotics
Anti-Coagulant
Prevent the growth of a clot hours for the effect to fully develop (Heaprin immediate)
Vitamin K Antagonists
(factor II, VII, IX, X)
Warfarin (Coumadin), Acenocoumarol (Sintrom)
Direct Thrombin Inhibitors
Bivalarudin (Angiomax), Ioxaglate (Hexabrix)
Factor Xa
Inhibitors
Direct
Fondaparinox (Arixtra)
Heparin
LMWH, Enoxaparin (Lovenox)

13. Anti-Thrombotic Review
Anti-Thrombotics
Thrombolytics
Reduce the size of the clot (dissolve) Administered together with Heparin for hours
Activates the enzyme plasminogen,
clearing the fibrin mesh,
making the clot soluble
and subject to further degradation
Streptokinase, Reteplase (Retavase)

14. Anti-Thrombotic Review
Anti-Thrombotics
Anti-Platelet
Anti-coagulant
Thrombolytic
Gp IIb/IIIa Inhibitors
Vitamin K Antagonists
(factor II, VII, IX, X)
Activates the enzyme plasminogen,
clearing the fibrin mesh,
making the clot soluble
and subject to further degradation
ADP Receptor Inhibitors
Direct Thrombin Inhibitors
Direct Thrombin Inhibitors
Prostglandin Receptor Inhibitors
Factor Xa
Inhibitors
Factor Xa
Inhibitors
COX Inhibitors
No Platelet Activation
No Platelet Activation
Heparin
Direct

15. Anti-Thrombotic & Anti-Coagulant Properties
If Hexabrix provides the same benefit as these other therapies….
What is the benefit of using Hexabrix too??

16. Anti-Thrombotic Review
Situations where these therapies don’t have time to take effect (ACS Patients)
Additive, synergistic effects with Reopro & Plavix
If you are already doing everything you can to prevent thrombotic complications, why not use a CM that provides & enhances protection?
Simple Choice
Significant Clinical Impact

17. Anti-Thrombotic Review
Can you go too far & increase bleeding risk?
Localized effect, not systemic
No lingering coagulation interference once CM clears the system
Marginal impact on activated clotting time