25.03.1 Anti-Thrombosis Treatments

Thrombosis occurs when there is formation of an unwanted blood clot (thrombus) or movement of an existing clot to a location where it can block important blood vessels. When there is damage to a blood vessel, a number of co-ordinated processes occur, resulting in the formation of a fibrin-platelet thrombus plug that facilitates cessation of bleeding (haemostasis) at the site of injury. This process includes movement of platelets to the site of injury and their adhesion to, and covering of, the exposed collagen of the subendothelial tissues via binding to von Willebrand factor and glycoprotein Ib (GpIb). The platelets then become active and release a variety of chemoattractants including ADP, thromboxane A2, serotonin and platelet activating factor (PAF) which in turn mobilise other platelets to the site of injury where they begin to adhere and aggregate into the growing clot via GpIIb/IIIa platelet receptors. Fibrinogen, a soluble plasma protein, simultaneously binds to GpIIb/IIIa receptors on two separate platelets resulting in platelet crosslinking and further platelet aggregation. Activation of the clotting cascade ultimately results in thrombin production from its precursor prothrombin. Thrombin, in turn, converts fibrinogen in the growing thrombus to fibrin, consolidating and stabilising the platelet plug.

There are three drug treatments used to prevent formation of clots or to dissolve established thrombi. These are the anti-platelet drugs, the anticoagulents and the thrombolytics.