Richard O Francis1, Sonia Mahajan2, Francesca Rapido1,3, Francesca La Carpia1, Mark Soffing2, Chaitanya Divgi2, Randy Yeh2, Akiva Mintz2, Lenhurst Leslie2, Irina Agrest2, Matthew S Karafin4, Yelena Ginzburg5, Beth H Shaz6, Steven L Spitalnik1, Joseph Schwartz1, Tiffany Thomas1, Xiaoyun Fu7, Pascal Amireault8,9, Pierre Buffet8,10, James C Zimring7, Angelo D'Alessandro11, Eldad A Hod1. 1. Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York. 2. Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York. 3. Pôle Neuroscience Tête et Cou, Département d'Anesthésie -Réanimation Hôpital Gui de Chauliac- Centre Hospitalier Universitaire, Montpellier, France. 4. Versiti Medical Sciences Institute, Milwaukee, Wisconsin. 5. Division of Hematology Oncology, Icahn School of Medicine at Mount Sinai, New York, New York. 6. New York Blood Center, New York, New York. 7. BloodWorks Northwest, Seattle, Washington. 8. Biologie Intégrée du Globule Rouge UMR_S1134, INSERM, Univ. Paris Diderot, Sorbonne Paris Cité, Univ. de la Réunion, Univ. des Antilles, Institut National de la Transfusion Sanguine, Laboratory of Excellence GR-Ex, Paris, France. 9. Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications U1163/CNRS ERL 8254, INSERM, CNRS, Univ Paris Descartes, Sorbonne Paris Cité, Paris, France. 10. Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 11. University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado.
Abstract
BACKGROUND: The chromium-51-labeled posttransfusion recovery (PTR) study has been the gold-standard test for assessing red blood cell (RBC) quality. Despite guiding RBC storage development for decades, it has several potential sources for error. METHODS: Four healthy adult volunteers each donated an autologous, leukoreduced RBC unit, aliquots were radiolabeled with technetium-99m after 1 and 6 weeks of storage, and then infused. Subjects were imaged by single-photon-emission computed tomography immediately and 4 hours after infusion. Additionally, from subjects described in a previously published study, adenosine triphosphate levels in transfusates infused into 52 healthy volunteers randomized to a single autologous, leukoreduced, RBC transfusion after 1, 2, 3, 4, 5, or 6 weeks of storage were correlated with PTR and laboratory parameters of hemolysis. RESULTS: Evidence from one subject imaged after infusion of technetium-99m-labeled RBCs suggests that, in some individuals, RBCs may be temporarily sequestered in the liver and spleen immediately following transfusion and then subsequently released back into circulation; this could be one source of error leading to PTR results that may not accurately predict the true quantity of RBCs cleared by intra- and/or extravascular hemolysis. Indeed, adenosine triphosphate levels in the transfusates correlated more robustly with measures of extravascular hemolysis in vivo (e.g., serum iron, indirect bilirubin, non-transferrin-bound iron) than with PTR results or measures of intravascular hemolysis (e.g., plasma free hemoglobin). CONCLUSIONS: Sources of measurement error are inherent in the chromium-51 PTR method. Transfusion of an entire unlabeled RBC unit, followed by quantifying extravascular hemolysis markers, may more accurately measure true posttransfusion RBC recovery.
BACKGROUND: The chromium-51-labeled posttransfusion recovery (PTR) study has been the gold-standard test for assessing red blood cell (RBC) quality. Despite guiding RBC storage development for decades, it has several potential sources for error. METHODS: Four healthy adult volunteers each donated an autologous, leukoreduced RBC unit, aliquots were radiolabeled with technetium-99m after 1 and 6 weeks of storage, and then infused. Subjects were imaged by single-photon-emission computed tomography immediately and 4 hours after infusion. Additionally, from subjects described in a previously published study, adenosine triphosphate levels in transfusates infused into 52 healthy volunteers randomized to a single autologous, leukoreduced, RBC transfusion after 1, 2, 3, 4, 5, or 6 weeks of storage were correlated with PTR and laboratory parameters of hemolysis. RESULTS: Evidence from one subject imaged after infusion of technetium-99m-labeled RBCs suggests that, in some individuals, RBCs may be temporarily sequestered in the liver and spleen immediately following transfusion and then subsequently released back into circulation; this could be one source of error leading to PTR results that may not accurately predict the true quantity of RBCs cleared by intra- and/or extravascular hemolysis. Indeed, adenosine triphosphate levels in the transfusates correlated more robustly with measures of extravascular hemolysis in vivo (e.g., serum iron, indirect bilirubin, non-transferrin-bound iron) than with PTR results or measures of intravascular hemolysis (e.g., plasma free hemoglobin). CONCLUSIONS: Sources of measurement error are inherent in the chromium-51 PTR method. Transfusion of an entire unlabeled RBC unit, followed by quantifying extravascular hemolysis markers, may more accurately measure true posttransfusion RBC recovery.
Authors: Nareg H Roubinian; Colleen Plimier; Jennifer P Woo; Catherine Lee; Roberta Bruhn; Vincent X Liu; Gabriel J Escobar; Steven H Kleinman; Darrell J Triulzi; Edward L Murphy; Michael P Busch Journal: Blood Date: 2019-07-26 Impact factor: 22.113
Authors: Angelo D'Alessandro; Xiaoyun Fu; Julie A Reisz; Tamir Kanias; Grier P Page; Mars Stone; Steve Kleinman; James C Zimring; Michael Busch Journal: Transfusion Date: 2020-05-11 Impact factor: 3.157
Authors: Richard O Francis; Angelo D'Alessandro; Andrew Eisenberger; Mark Soffing; Randy Yeh; Esther Coronel; Arif Sheikh; Francesca Rapido; Francesca La Carpia; Julie A Reisz; Sarah Gehrke; Travis Nemkov; Tiffany Thomas; Joseph Schwartz; Chaitanya Divgi; Debra Kessler; Beth H Shaz; Yelena Ginzburg; James C Zimring; Steven L Spitalnik; Eldad A Hod Journal: J Clin Invest Date: 2020-05-01 Impact factor: 14.808
Authors: Zachary C Bitan; Alice Zhou; Donald J McMahon; Debra Kessler; Beth H Shaz; Elise Caccappolo; Joseph Schwartz; Richard O Francis; Gary M Brittenham; Steven L Spitalnik; Eldad A Hod Journal: Blood Transfus Date: 2019-07 Impact factor: 3.443
Authors: Lorenzo Bertolone; Micaela Kalani Roy; Ariel M Hay; Evan J Morrison; Davide Stefanoni; Xiaoyun Fu; Tamir Kanias; Steve Kleinman; Larry J Dumont; Mars Stone; Travis Nemkov; Michael P Busch; James C Zimring; Angelo D'Alessandro Journal: Transfusion Date: 2020-04-27 Impact factor: 3.157