MECHANISM OF ACTION OF THROMBIN ON PLATELETS*

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Abstract
Thrombin added to platelet-rich plasma produced platelet aggregation prior to clotting of the plasma, provided free divalent cation was present. Addition of appropriate amounts of thrombin to citrated platelet-rich plasma containing small amounts of heparin produced platelet aggregation even though coagulation of the plasma never occurred. The number of morphologically intact platelets recovered after addition of thrombin to platelet-rich plasma was inversely related to the concentration of thrombin. A large number ( 70%) of morphologically intact and functionally active platelets were recovered after lysis of nonretracted clots formed in the absence of free divalent cation. A smaller number of intact platelets was recovered after lysis of retracted clots formed in the presence of free divalent cation. Platelets incubated with trypsin remained morphologically intact. Nontrypsinized platelets in normal serum were aggregated by thrombin. Trypsinized platelets in normal serum were not aggregated by thrombin. Trypsinized platelets supported retraction of clots formed from either plasma or purified fibrinogen. The histologic changes associated with clotting and retraction were similar with trypsinized and nontrypsinized platelets. Extracts of nontrypsinized platelets contained thrombin-clottable protein (platelet fibrinogen). Extracts of trypsinized platelets did not contain platelet fibrinogen. These results suggest that the substrate for the action of thrombin in the production of platelet aggregation and clot retraction is a protein clottable by thrombin similar to or identical with fibrinogen, and situated on the surface of the platelets.