ThrombinIts Key Role in Thrombogenesis-Implications for Its Inhibition

This new multi-authored book reviews the current understanding of the role of thrombin in venous and arterial thrombosis and its inhibition in the clinical setting. Heparin, the most widely used antithrombotic, does not effectively regulate thrombin or its formation. Accumulating evidence suggests that other antithrombins are effective in some of the situations where heparin is not. Discussions include the current knowledge on antithrombotic prophylaxis and therapy, from the perspective of the role in thrombin in venous and arterial vascular disease, the limitations of the current anticoagulant therapies, and potential and limitations of newer antithrombins currently being tested in several experimental and clinical settings. Thrombin helps the clinician to better rationalize the use of specific antithrombins in the prevention and management of thrombotic disease and provides the basic scientist with a better understanding of the goals the clinician attempts to achieve with antithrombotic therapy.

Table of Contents:

Thrombin-Catalyzed Amplification and Inhibitory Reactions of Blood Coagulation, F.A. Ofosu, M.R. Buchanan, and S.J. Brister
Introduction
Acceleration of Blood Coagulation
Summary
The Structural Basis for Thrombin Inhibition by Hirudin and Serpins, M.T. Stubbs and W. Bode
Introduction
Thrombin Structure and Its Sites of Interaction
Interaction with Fibrinogen
Interaction with Hirudin
Interaction with Serpins
Summary
Development and Rationale for the Use of Low Molecular Weight Heparins in the Prevention and Treatment of Venous Thrombosis, J.R. Leclerc
Introduction
Unfractionated Heparin
Low Molecular Weight Heparins
Mechanism of Action
Advantages of Low Molecular Weight Heparin
Clinical Studies
Heparin Cofactor II and the Prevention and Treatment of Thrombosis, M.R. Buchanan, S.J. Brister, and F.A. Ofosu
Introduction
Why Target Thrombin for Inhibition?
The Basis for Antithrombotic Therapy
Inhibition of Surface-Bound Thrombin
Thrombin HCII Inhibition
Inhibition of Thrombin by Heparin Cofactor II: Effect on Thrombus Formation/Growth in the Experimental Setting
Conclusion
Future Directions
Development and Rationale for the Use of Direct Thrombin Inhibitors in the Prevention and Treatment of Arterial and Venous Thrombosis, J.S. Ginsberg
Introduction
Clinical Studies of Direct Thrombin Inhibitors
Development and Rationale for Use of Anti-Thrombins in Arterial Thrombosis, S.J. Brister, F.A. Ofosu, and M.R. Buchanan
Introduction
The Prothrombotic State
Regulation of the Prothrombotic State
Conclusion
Pediatric Thromboembolism: Epidemiology, Prevention and Treatment, M. Andrew and M. David
Introduction
The Relationship Between Age and the Occurrence of DVT/PE
Mechanisms Protecting Children from Thromboembolic Complications
The Epidemiology of DVT/PE in Children
Clinical Outcome
Conclusion
The Role of Thrombin Inhibition in Thrombolytic Therapy, M. Pr