Prekallikrein activator (Hageman factor fragment) in human plasma fractions

The recent finding that hypotensive reactions to blood products can be attributed to the presence of a prekallikrein activator in the products, prompted us to measure the distribution of this substance among plasma fractions produced by the cold ethanol method. While the levels observed varied among different production lots, prekallikrein activator was found to be present in four lots of fibrinogen, four lots of immune serum globulin, one lot of immune serum globulin for intravenous use, and nine lots of antihemophilic factor. Nineteen lots of 25% albumin were tested and found to be free of detectable amounts of prekallikrein activator. In addition to 25% albumin and the fraction V rework fractions leading to it, only supernatant III from the fraction II + III reworks was found to be free of the prekallikrein activator. All other fractions contained significant amounts of activity. Chloroform treatment, used to move kallikrein inhibitors was found to destroy the prekallikrein activator in fractions with low protein levels. The prekallikrein activator in antihemophilic factor preparations was formed during contact with glass, and its behavior led to the conclusion that these concentrates contained Hageman factor (Factor XII).