title: Impact of Triton X-100 on alpha 2-antiplasmin (SERPINF2) activity in solvent/detergent-treated plasma.
abstract: Large-pool solvent/detergent (SD) plasma for transfusion exhibits reduced alpha 2-antiplasmin (alpha2-AP; SERPINF2) functional activity. The reason for the loss of alpha2-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 alpha2-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 4h. 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 alpha2-AP activity. TnBP, Triton X-100, and Triton X-45 were measured at all stages of the processes to evaluate potential interferences with the alpha2-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 alpha2-AP activity. In conclusion, the agent altering alpha2-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 alpha2-AP activity.
authors.affiliation: Research Department, Human Plasma Product Services, 18 rue Saint Jacques, 59800 Lille, France. tburnou@attglobal.net
authors.forename: Thierry
authors.initials: T
authors.lastname: Burnouf
authors.forename: Hadi Alphonse
authors.initials: HA
authors.lastname: Goubran
authors.forename: Miryana
authors.initials: M
authors.lastname: Radosevich
authors.forename: Makram A
authors.initials: MA
authors.lastname: Sayed
authors.forename: George
authors.initials: G
authors.lastname: Gorgy
authors.forename: Magdy
authors.initials: M
authors.lastname: El-Ekiaby
mesh_terms: D001803:Blood Transfusion; D003902:Detergents / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D017830:Octoxynol / Q000494:pharmacology*; D010755:Organophosphates; D010949:Plasma / Q000187:drug effects; D012997:Solvents; D038301:Virus Inactivation / Q000187:drug effects; D000979:alpha-2-Antiplasmin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D003902:Detergents; D010755:Organophosphates; D012997:Solvents; D000979:alpha-2-Antiplasmin; D017830:Octoxynol; C009524:tributyl phosphate