Thrombus models and mechanisms of action of anti-platelet drugs.

Thrombus formation is initiated by platelet aggregation, followed by activation of the blood coagulation system, so that anti-thrombotic drugs can be classified into anti-platelet drugs, anti-coagulation drugs and fibrinolytic drugs. A variety of thrombus models in animals have been reported. Microthrombus formation in arterioles in the microcirculation is useful for analyzing the nature of the thrombus and the process of thrombus formation. Platelet aggregation can be divided into two types: (a) reversible aggregation (Rev-Aggr), in which platelets do not release their granular contents and are able to return to the resting discoid shape and (b) irreversible aggregation (Irrev-Aggr), in which platelets release their granular contents. Irrev-Aggr is inhibited by aspirin and not by PGI2 at the maximum aggregation, whereas Rev-Aggr is not inhibited by aspirin and inhibited by PGI2 even at the maximum aggregation. Thrombi corresponding to either type of platelet aggregation can be produced in arterioles in the microcirculation. An ADP-induced thrombus, which is composed of Rev-Aggr of platelets and disaggregated automatically, is not inhibited by indomethacin, but inhibited by PGI2. In contrast, a stable thrombus, which is composed of Irrev-Aggr of platelets and keeps its initial shape for a longer period, is sensitive to indomethacin, but resistant to PGI2. Thus, anti-thrombotic drugs should be developed and used for targeting the individual processes of thrombus formation.