The importance of activation of antihemophilic globulin and proaccelerin by traces of thrombin in the generation of intrinsic prothrombinase activity.

seconds.2 Therefore, although the PTT measures the over-all time of the intrinsic clotting reactions, in most circumstances it essentially measures the rate of generation of intrinsic prothrombinase. It is now generally accepted that contact with a negatively charged surface such as glass initiates clotting in vitro by activating Hageman factor ( HF, factor XII ) . Activated HF then reacts with plasma thromboplastin antecedent ( PTA, factor XI ), and possibly with a third factor,3 to form an intermediate Vilich has been called activation product ( AP ) .“ Recent evidence suggests that AP is activated PTA.5 Intrinsic coagulation proceeds rapidly once AP has formed. For example, Waaler has shown4 that the 150-second PTT of intact plasma ( plasma which has not been in contact with a negatively charged surface ) shortens to about 40 seconds in the presence of potent AP. Generation of AP removes the initial block to intrinsic clotting in vitro. The experiments reported herein were undertaken to investigate why traces of thrombin also shorten the PTT.1 Data will be presented which prove that minute quantities of thrombin enhance coagulability by activating both antihemophilic globulin ( AHG, factor VIII ) and proaccelerin ( factor V ) . It will be shown tilat these activations bypass a second, important time-consuming step in the generation of intrinsic prothrombinase.