Enzymatic Basis for Platelet Aggregation and Release: The Significance of the ‘Platelet Atmosphere’ and the Relationship between Platelet Function and Blood Coagulation

S ummary . Blood coagulation and platelet reactions such as aggregation and release are both essential to haemostasis and, although relationships between these two processes have been demonstrated, they have been regarded as different phenomena. The results reported here show that the two are inseparable, and that platelet aggregation and release are dependent on the ‘plasmatic atmosphere’ of coagulation factors surrounding platelets. Test systems were developed for studying platelets in plasma (Han & Ardlie, 1973) and in artificial media. When coagulation factors were removed from platelets by washing, only slight reversible aggregation occurred upon the addition of ADP and fibrinogen. Trace amounts of thrombin restored aggregation and TAMe completely inhibited aggregation. Irreversible aggregation and the release reaction of platelets were shown to be dependent on the generation of thrombin by the interaction of clotting factors on the platelet surface. Polymerizing fibrin caused irreversible aggregation and, conversely, inhibitors of fibrin polymerization prevented irreversible aggregation. Irreversible aggregates were insoluble in 5 M urea and 1% monochloroacetic acid suggesting involvement of factor XIII in this aspect of aggregation. It is proposed that aggregation of platelets by ADP is mediated initially by thrombin‐fibrinogen complexes between adjacent adhering platelets. It is also proposed that the nature of the bond between platelets changes when the enzymatic phase of the thrombin—fibrinogen reaction is followed by the polymerization phase, and aggregation then becomes irreversible under the influence of factor XIII, activated by thrombin. Thrombin action also results in the release of platelet constituents. A scheme for haemostasis which emerges from this unification of platelet reactions and blood coagulation is presented in Fig 15, and possible ways in which various other platelet and plasma factors may be involved in haemostasis are briefly discussed.