There are two major time-consuming steps in intrinsic clotting in vitro. The importance of the first step—the triggering of intrinsic clotting through the generation of activation product (AP) activity—has been appreciated for several years. This paper has been concerned with the delineation of the second important time-consuming step—the generation of a trace of thrombin, which by activating both anti-hemophilic globulin (AHG, factor VIII ) and proaccelerin (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 platelet factor 3-like activity, all of the remaining reactions required to generate powerful intrinsic prothrombinase activity take place within 7 to 12 seconds after recalcification. It may well be that AHG and proaccelerin must be activated by minute traces of thrombin before they can participate effectively in the generation of intrinsic prothrombinase activity.

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