Thrombin generation and secretion of platelet Factor 4 during blood clotting.

Abstract

We have studied the platelet release reaction and thrombin generation during the spontaneous clotting of whole blood in vitro. Both thrombin formation and secretion of platelet Factor 4 were detected at least 12 min before clotting (clotting time, 22--26 min). Initially, at low thrombin concentrations (2--5 ng/ml), there is a small increase in plasma platelet Factor 4 (less than 1% of the amount present in serum). This is followed by a gradual increase in both platelet Factor 4 and thrombin concentrations over a 12 to 20-min interval. Finally, 5 min 5 before clotting, there is a rapid increase in both thrombin generation and platelet secretion. Thus, we have shown that the release of platelet Factor 4 is a prolonged reactoin and the extent to which it occurs parallel thrombin generation. It is only when thrombin concentrations are high (45--90) ng/ml)--during the period of clot formation--that the major part of platelet Factor 4 secretion occurs. Release of platelet Factor 4, like fibrin formation, occurs in the last step of in vitro coagulation.