Prekallikrein Activator in Human Albumin Prepared by Cold-Ethanol Precipitation Methods and by ION Exchange Chromatography

Hypotensive reactions associated with the administration of albumin-containing plasma fractions have been attributed by Alving et al. to the presence of Hageman-factor fragments or prekallikrein activator (PKA). Using a radiochemical assay which measures kallikrein activation, we have investigated the PKA content of plasma fractions prepared according to the cold-ethanol method 6 of Cohn et al., several modified cold-ethanol procedures, and the ion-exchange chromatography system of Curling et al. Cohn fraction IV-4 contains both PKA and a precursor from which PKA activity can be generated by kaolin treatment, while Cohn Fraction V is free of both of these entities. Modification of Cohn method 6 by combining the IV-1 and IV-4 precipitation steps results in less efficient removal of PKA, especially when strong acids and bases replace acetate buffers for pH control. Prekal1ikrein activator activity accompanies albumin throughout the ion-exchange purification procedure and is present in the final albumin product prepared by this method. These results explain why PKA occurs frequently in the derivative known as plasma protein fraction and rarely in albumin which has been made according to Cohn method 6.