ABC of Antithrombotic Therapy

Many of the common problems in clinical practice today relate to thrombosis. The underlying final pathophysiological process in myocardial infarction and stroke is thrombus formation (thrombogenesis). Common cardiovascular disorders such as atrial fibrillation and heart failure are also associated with thrombogenesis. Thrombosis is also a clinical problem in various cancers and after surgery, especially orthopaedic. Pathophysiology Over 150 years ago Virchow recognised three prerequisites for thrombogenesis: abnormal blood flow, vessel wall abnormalities, and blood constituent abnormalities. This concept has been extended by modern knowledge of the endothelial function, flow characteristics, and blood constituents including haemorheological factors, clotting factors, and platelet physiology. As thrombus consists of platelets and fibrin (and often bystanding erythrocytes and white blood cells), optimum antithrombotic prophylactic therapy can and should be directed towards both.

Antiplatelet drugs Aspirin and agents acting on the cyclo-oxygenase pathway Aspirin irreversibly inhibits cyclo-oxygenase by acetylation of amino acids that are next to the active site. In platelets, this is the rate limiting step in synthesis of thromboxane A2, and inhibition occurs in the megakaryocyte so that all budding platelets are dysfunctional. Because platelets are unable to regenerate fresh cyclo-oxygenase in response, the effect of aspirin remains as long as the lifespan of the platelet (generally about 10 days).