Thrombin physiology and pathophysiology

Abstract

Objectives: To review the role of thrombin in physiology and clinical disease and to discuss the pharmacology of antithrombosis.

Data sources: Original research articles, scientific reviews, textbooks.

Human data synthesis: Thrombin and thrombin receptors are involved in a variety of physiologic and pathologic processes resulting in a great deal of interest in thrombin-related pharmacologic intervention.

Veterinary data synthesis: Although there is little clinical research data available on thrombin specifically in veterinary patients, some of the original research on protease activated receptors was performed at veterinary institutions and many of the human molecular biology studies have been done on animals including dogs.

Conclusion: Thrombin plays a significant role in coagulation, anticoagulation, and fibrinolysis. Antithrombotic treatment is focused on preventing thrombosis while maintaining hemostasis. Pharmaceutical agents are selected for the specific component of the coagulation pathway associated with a specific disease process, for a proven prophylactic benefit with procedures that carry a risk of thromboembolism, for rapidity of onset and ease of reversibility, for limited monitoring requirements, and for oral formulation and bioavailablity. Recent insight into other aspects of thrombin physiology presents an opportunity for pharmacologic intervention in a variety of other processes such as inflammation and sepsis, peripheral blood cell activation and chemotaxis, vascular endothelial and smooth muscle activity, cellular development and tissue repair, mitogenesis, neoplasia, and the function of nervous tissue following injury.