Thomas Thiele1, Gregor Hron2, Sarah Kellner3, Christina Wasner4, Antje Westphal1, Theodore E Warkentin5, Andreas Greinacher1, Kathleen Selleng1. 1. Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany. 2. Department of Internal Medicine A, Ernst-Moritz-Arndt University, Greifswald, Germany. 3. Department of Internal Medicine B, Ernst-Moritz-Arndt University, Greifswald, Germany. 4. Institute for Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany. 5. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
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. MATERIALS AND 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. DISCUSSION: 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.
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. MATERIALS AND 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. DISCUSSION: 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: Nena Matijevic; Yao-Wei W Wang; Vadim Kostousov; Charles E Wade; K Vinod Vijayan; John B Holcomb Journal: Thromb Res Date: 2011-03-21 Impact factor: 3.944
Authors: C Buchta; M Felfernig; P Höcker; M Macher; G F Körmöczi; P Quehenberger; H Heinzl; P Knöbl Journal: Vox Sang Date: 2004-10 Impact factor: 2.144
Authors: Ute Gravemann; Manuela Kusch; Herbert Koenig; Harald Mohr; Thomas H Mueller Journal: Transfus Med Hemother Date: 2009-03-04 Impact factor: 3.747
Authors: H C Hemker; P Giesen; R AlDieri; V Regnault; E de Smed; R Wagenvoord; T Lecompte; S Béguin Journal: Pathophysiol Haemost Thromb Date: 2002 Sep-Dec