Evidence that colagen releases human platelet constituents by two different mechanisms

Collagen is believed to be involved in the initial events in haemostasis and has been shown by others to cause platelet aggregation and release, and also to initiate the intrinsic pathway of coagulation. The present experiments provide evidence whihc suggests how these many effects of collagen may be involved in haemostasis. It is shown here that collagen releases platelet constituents by two different pathways. Collagen causes platelets washed free of loosely adsorbed coagulation factors to release constituents. This activity, is therefore, independent of the intrinsic pathway of coagulation, and is not inhibited by heparin or hirudin. Collagen also releases platelet constituents by an alternative pathway which is inhibited by heparin and hirudin and is independent of factor XII, but is dependent on factor XI, subsequent factors in the intrinsic pathway of coagulation and calcium. These results suggest that collagen-induced release of platelet constituents is in part due to a direct effect on the platelet, and , in part, to an indirect effect involving coagulation factors and mediated by thrombin. The present results suggest that irreversible aggregation by collagen is also mediated by thrombin. The possible significance of this dual action of collagen in the haemostatic process is shown in Fig 7.