Philip J Norris1,2,3, Ken Schechtman4,5, Heather C Inglis1, Avril Adelman4, John W Heitman1, Ryan Vilardi6, Avani Shah1, Nareg H Roubinian1, Ali Danesh1, Anne M Guiltinan1, Sheila M Keating1, Jacques Lacroix7, Mitchell J Cohen6, Philip C Spinella8. 1. Vitalant Research Institute, University of California, San Francisco, California. 2. Department of Laboratory Medicine, University of California, San Francisco, California. 3. Department of Medicine, University of California, San Francisco, California. 4. Department of Biostatistics, Washington University School of Medicine, St. Louis, Missouri. 5. Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. 6. Department of Surgery, University of California, San Francisco, California. 7. Centre Hospitalier Universitaire (CHU) Sainte-Justine, Université de Montréal, Montreal, Canada. 8. Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
Abstract
BACKGROUND: Several retrospective studies have suggested that transfusion with red blood cells (RBCs) stored for longer periods is associated with increased mortality. The Age of Blood Evaluation (ABLE) study randomized subjects to receive fresh vs. standard issue RBC units and showed no difference in the primary or secondary endpoints of mortality or change in multi-organ dysfunction syndrome (MODS) score. METHODS: In this study a subset of 100 ABLE subjects were enrolled to measure coagulation and immune parameters. Samples were collected pre-transfusion and on days 2, 6, 28, and 180 post-transfusion. Levels of 16 coagulation parameters, regulatory and functional T cells, 25 cytokines, and 16 markers of extracellular vesicles (EVs) were determined. RESULTS: Changes from baseline in levels of protein C, factor V, and EVs expressing phosphatidyl serine and CTLA-4 (CD152) differed between recipients of fresh and standard storage age RBC units, with the vast majority of coagulation and EV markers and all cytokines tested showing no difference between study arms. Although most analytes showed no difference between subjects in the fresh and standard arms of the study, 6 coagulation parameters, 15 cytokines, and 7 EV parameters changed significantly in the period post-transfusion. DISCUSSION: Transfusion of fresh vs. standard issue RBC units does not result in substantial changes in coagulation or immune parameters, up to day 35 of RBC storage. Furthermore, significant changes in multiple coagulation and immune parameters are detectable post-transfusion, though causality cannot be determined based on the current study.
BACKGROUND: Several retrospective studies have suggested that transfusion with red blood cells (RBCs) stored for longer periods is associated with increased mortality. The Age of Blood Evaluation (ABLE) study randomized subjects to receive fresh vs. standard issue RBC units and showed no difference in the primary or secondary endpoints of mortality or change in multi-organ dysfunction syndrome (MODS) score. METHODS: In this study a subset of 100 ABLE subjects were enrolled to measure coagulation and immune parameters. Samples were collected pre-transfusion and on days 2, 6, 28, and 180 post-transfusion. Levels of 16 coagulation parameters, regulatory and functional T cells, 25 cytokines, and 16 markers of extracellular vesicles (EVs) were determined. RESULTS: Changes from baseline in levels of protein C, factor V, and EVs expressing phosphatidyl serine and CTLA-4 (CD152) differed between recipients of fresh and standard storage age RBC units, with the vast majority of coagulation and EV markers and all cytokines tested showing no difference between study arms. Although most analytes showed no difference between subjects in the fresh and standard arms of the study, 6 coagulation parameters, 15 cytokines, and 7 EV parameters changed significantly in the period post-transfusion. DISCUSSION: Transfusion of fresh vs. standard issue RBC units does not result in substantial changes in coagulation or immune parameters, up to day 35 of RBC storage. Furthermore, significant changes in multiple coagulation and immune parameters are detectable post-transfusion, though causality cannot be determined based on the current study.
Authors: Ali Danesh; Heather C Inglis; Rachael P Jackman; Shiquan Wu; Xutao Deng; Marcus O Muench; John W Heitman; Philip J Norris Journal: Blood Date: 2013-12-12 Impact factor: 22.113
Authors: Rachael P Jackman; Garth H Utter; Marcus O Muench; John W Heitman; Matthew M Munz; Robert W Jackman; Hope H Biswas; Ryan M Rivers; Leslie H Tobler; Michael P Busch; Philip J Norris Journal: Transfusion Date: 2012-03-27 Impact factor: 3.157
Authors: Dean A Fergusson; Paul Hébert; Debora L Hogan; Louise LeBel; Nicole Rouvinez-Bouali; John A Smyth; Koravangattu Sankaran; Alan Tinmouth; Morris A Blajchman; Lajos Kovacs; Christian Lachance; Shoo Lee; C Robin Walker; Brian Hutton; Robin Ducharme; Katelyn Balchin; Tim Ramsay; Jason C Ford; Ashok Kakadekar; Kuppuchipalayam Ramesh; Stan Shapiro Journal: JAMA Date: 2012-10-10 Impact factor: 56.272
Authors: Marion C Lanteri; John W Heitman; Rachel E Owen; Thomas Busch; Nelly Gefter; Nancy Kiely; Hany T Kamel; Leslie H Tobler; Michael P Busch; Philip J Norris Journal: J Infect Dis Date: 2008-05-01 Impact factor: 5.226
Authors: Wenzhong Xiao; Michael N Mindrinos; Junhee Seok; Joseph Cuschieri; Alex G Cuenca; Hong Gao; Douglas L Hayden; Laura Hennessy; Ernest E Moore; Joseph P Minei; Paul E Bankey; Jeffrey L Johnson; Jason Sperry; Avery B Nathens; Timothy R Billiar; Michael A West; Bernard H Brownstein; Philip H Mason; Henry V Baker; Celeste C Finnerty; Marc G Jeschke; M Cecilia López; Matthew B Klein; Richard L Gamelli; Nicole S Gibran; Brett Arnoldo; Weihong Xu; Yuping Zhang; Steven E Calvano; Grace P McDonald-Smith; David A Schoenfeld; John D Storey; J Perren Cobb; H Shaw Warren; Lyle L Moldawer; David N Herndon; Stephen F Lowry; Ronald V Maier; Ronald W Davis; Ronald G Tompkins Journal: J Exp Med Date: 2011-11-21 Impact factor: 14.307