title: Thrombin generation, ProC(®)Global, prothrombin time and activated partial thromboplastin time in thawed plasma stored for seven days and after methylene blue/light pathogen inactivation.
abstract: BACKGROUND
  Methylene blue pathogen inactivation and storage of thawed plasma both lead to changes in the activity of several clotting factors. We investigated how this translates into a global loss of thrombin generation potential and alterations in the protein C pathway.
  
  
  METHODS
  Fifty apheresis plasma samples were thawed and each divided into three subunits. One subunit was stored for 7 days at 4 °C, one was stored for 7 days at 22 °C and one was stored at 4 °C after methylene blue/light treatment. Thrombin generation parameters, ProC(®)Global-NR, prothrombin time and activated partial thromboplastin time were assessed on days 0 and 7.
  
  
  RESULTS
  The velocity of thrombin generation increased significantly after methylene blue treatment (increased thrombin generation rate; time to peak decreased) and decreased after storage (decreased thrombin generation rate and peak thrombin; increased lag time and time to peak). The endogenous thrombin generation potential remained stable after methylene blue treatment and storage at 4 °C. Methylene blue treatment and 7 days of storage at 4 °C activated the protein C pathway, whereas storage at room temperature and storage after methylene blue treatment decreased the functional capacity of the protein C pathway. Prothrombin time and activated partial thromboplastin time showed only modest alterations.
  
  
  CONCLUSIONS
  The global clotting capacity of thawed plasma is maintained at 4 °C for 7 days and directly after methylene blue treatment of thawed plasma. Thrombin generation and ProC(®)Global are useful tools for investigating the impact of pathogen inactivation and storage on the clotting capacity of therapeutic plasma preparations.
authors.affiliation: Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thiele
authors.affiliation: Department of Internal Medicine A, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Hron
authors.affiliation: Department of Internal Medicine B, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kellner
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Wasner
authors.affiliation: Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Westphal
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
authors.affiliation: Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
authors.affiliation: Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Selleng
mesh_terms: D001780:Blood Coagulation Tests; D001793:Blood Preservation / Q000379:methods*; D015925:Cryopreservation / Q000379:methods; D006801:Humans; D008027:Light; D008751:Methylene Blue / Q000494:pharmacology*; D010314:Partial Thromboplastin Time; D010949:Plasma / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D011486:Protein C / Q000378:metabolism; D011517:Prothrombin Time; D013242:Sterilization / Q000379:methods*; D013917:Thrombin / Q000378:metabolism*
chemical_list: D011486:Protein C; D013917:Thrombin; D008751:Methylene Blue