In vitro studies on the way in which the activation of factor VIII is affected in mixtures of plasma with hemophilia A plasma.

Factor VIII exchange test experiments with hemophilia A plasmas were performed to find out how the results were affected by submitting plasmas and plasma mixtures to different incubation periods at 37 degrees C, heat precipitation, and ether extraction. The experiments led to the following results: 1. In plasma mixtures, frequently higher factor VIII activities are found than can be expected from the single activities of the used plasmas. Activity increases are factor-specific. 2. The component to be activated is in the hemophilic plasma; the activity-increasing agent is in the normal plasma. These results lead to the hypothesis that hemophilia A patients have sufficient quantities of inactive factor VIII, but it stays inactive for lack of the necessary activator. In normal plasma the activator is in balance or surplus to the inactive factor. By adding normal plasma, thus supplying free activator, the inactive factor VIII of hemophilia A plasma can, under suitable conditions, be developed into active factor VIII.