The procoagulant effect of platelets on conversion of prothrombin to thrombin in nonanticoagulated plasma

The effects of normal platelets and dysfunctional platelets on the activities of prothrombin complex components (fluid-phase factor X, factor V, and prothrombin) and on prothrombin conversion products were studied in nonanticoagulated plasma by both functional and physical methods. Rapid centrifugation of small blood volumes at 24 degrees C yielded PRP and PPP before changes could be detected by functional and physical means. It was shown for the first time in native nonanticoagulated PRP that prothrombin and factor V consumption by functional assays depends on physiologically active platelets, since inhibition by PGE and theophylline or by dibutyryl cyclic AMP and acceleration by ADP was observed. These platelet-dependent phenomena occurred in two stages: (1) a decrease in factor V activity coinciding with platelet clumping and (2) a decrease in prothrombin activity simultaneous with clot appearance. Neither of these stages was clearly separated in recalcified citrated plasma. In studies of patients (Glanzmann's thrombasthenia, Hermansky-Pudlak syndrome, and Gray platelet syndrome) inhibition of the first stage and abnormalities in subsequent clotting events occurred only in Gray platelet syndrome patients, whose platelets carry a defect in alpha-granules. Finally, with [3H]prothrombin and SDS-PAGE, prothrombin conversion was found to be platelet-dependent and to proceed mainly through the factor Xa activation pathway.