title: Hemostatic properties and protein expression profile of therapeutic apheresis plasma treated with amotosalen and ultraviolet A for pathogen inactivation.
abstract: The INTERCEPT Blood System (IBS) using amotosalen-HCl and ultraviolet (UV)A inactivates a large spectrum of microbial pathogens and white blood cells in therapeutic plasma. Our aim was to evaluate to what extent IBS modifies the capacity of plasma to generate thrombin and induces qualitative or quantitative modifications of plasma proteins.
  
  
  
  Plasma units from four donors were collected by apheresis. Samples were taken before (control [CTRL]) and after IBS treatment and stored at -80°C until use. The activities of plasma coagulation factors and inhibitors and the thrombin generation potential were determined using assays measuring clotting times and the calibrated automated thrombogram (CAT), respectively. The proteomic profile of plasma proteins was examined using a two-dimensional differential in-gel electrophoresis (2D-DIGE) method.
  
  
  
  Nearly all of the procoagulant and antithrombotic factors tested retained at least 78% of their initial pre-IBS activity. Only FVII and FVIII displayed a lower level of conservation (67%), which nevertheless remained within the reference range for conventional plasma coagulation factors. The thrombin generation profile of plasma was conserved after IBS treatment. Among the 1331 protein spots revealed by 2D-DIGE analysis, only four were differentially expressed in IBS plasma compared to CTRL plasma and two were identified by mass spectrometric analysis as transthyretin and apolipoprotein A1.
  
  
  
  The IBS technique for plasma moderately decreases the activities of plasma coagulation factors and antithrombotic proteins, with no impact on the thrombin generation potential of plasma and very limited modifications of the proteomic profile.
authors.affiliation: UMR_S949, INSERM, Strasbourg, France.|EFS-Alsace-Lorraine-Champagne-Ardenne, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ohlmann
authors.affiliation: UMR_S949, INSERM, Strasbourg, France.|EFS-Alsace-Lorraine-Champagne-Ardenne, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Hechler
authors.affiliation: Plateforme Protéomique 3P5, Université Paris Descartes, Sorbonne Paris Cité|INSERM, U1016, Institut Cochin, Paris, France.|CNRS, UMR 8104, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chafey
authors.affiliation: UMR_S949, INSERM, Strasbourg, France.|EFS-Alsace-Lorraine-Champagne-Ardenne, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ravanat
authors.affiliation: EFS-Alsace-Lorraine-Champagne-Ardenne, Strasbourg, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Isola
authors.affiliation: Association ARMESA, Strasbourg, France.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Wiesel
authors.affiliation: Association ARMESA, Strasbourg, France. jean-pierre.cazenave@armesa.org.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cazenave
authors.affiliation: UMR_S949, INSERM, Strasbourg, France.|EFS-Alsace-Lorraine-Champagne-Ardenne, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Gachet
mesh_terms: D001779:Blood Coagulation Factors / Q000032:analysis; D001793:Blood Preservation / Q000379:methods*; D001798:Blood Proteins / Q000737:chemistry / Q000187:drug effects; D011564:Furocoumarins / Q000494:pharmacology*; D006801:Humans; D010949:Plasma / Q000737:chemistry*; D040901:Proteomics / Q000379:methods; D014466:Ultraviolet Rays
chemical_list: D001779:Blood Coagulation Factors; D001798:Blood Proteins; D011564:Furocoumarins; C118577:amotosalen