Impact of Triton X-100 on alpha 2-antiplasmin (SERPINF2) activity in solvent/detergent-treated plasma

Large-pool solvent/detergent (SD) plasma for transfusion exhibits reduced alpha 2-antiplasmin (alpha 2-AP; SERPINF2) functional activity. The reason for the loss of a2-AP has not been described and could be due to the SD incubation itself and/or to the processing steps implemented to remove the solvent and the detergent. We have studied a2-AP activity during six down-scale preparations of plasma virally-inactivated by 1% (v/v) TnBP combined with two different non-ionic detergents, either 1% Triton X-100 or 1% Triton X-45, at 31 degrees C for 4 h. The SD-treated plasmas were then extracted with 7.5% (v/v) soybean oil, centrifuged at 3800 x g for 30 min, and subjected to hydrophobic interaction chromatography (HIC) to remove the SD agents. Control runs without TnBP and Triton were performed to evidence possible impacts of each process step on alpha 2-AP activity. TnBP, Triton X-100, and Triton X-45 were measured at all stages of the processes to evaluate potential interferences with the alpha 2-AP assay. Alpha 2-AP activity was about 10% that of starting plasma after 1% TnBP-1% Triton X-100 incubation and about 50% after oil extractions, centrifugation, and HIC. By contrast about 73% of the antiplasmin activity was found after the incubation with 1% TnBP and 1% Triton X-45, 88% after removal of the SD agents by oil extractions, 90% after centrifugation and 92% after HIC. The control runs performed without SD agents showed that the process steps did not affect the a2-AP activity. In conclusion, the agent altering a2-AP activity in SD-plasma is Triton X-100. The choice of detergents for the SD viral inactivation of therapeutic plasma fractions used in patients at risk of fibrinolysis should consider the impact on a2-AP activity. (C) 2007 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.