The Importance of Activation of Antihemophilic Globulin and Proaccelerin by Traces of Thrombin in the Generation of Intrinsic Prothrombinase Activity

There are two major time-consuming steps in intrinsic clotting in vitro.The importance of the first step—the triggering of intrinsic clotting throughthe generation of activation product (AP) activity—has been appreciatedfor several years. This paper has been concerned with the delineation of thesecond important time-consuming step—the generation of a trace of thrombin,which by activating both anti-hemophilic globulin (AHG, factor VIII ) andproaccelerin (factor V ), shifts the intrinsic clotting process into high gear.Data have been presented which indicate that when plasma contains AP,activated AHG (AHG'), activated proaccelerin (accelerin ) and free plateletfactor 3-like activity, all of the remaining reactions required to generate powerful intrinsic prothrombinase activity take place within 7 to 12 seconds afterrecalcification. It may well be that AHG and proaccelerin must be activatedby minute traces of thrombin before they can participate effectively in thegeneration of intrinsic prothrombinase activity.

Submitted on May 14, 1962 Accepted on October 24, 1962