BACKGROUND: Exchange transfusion is a mainstay in the treatment of sickle cell anemia. Transfusion recipients with sickle cell disease (SCD) can be transfused over 10 units per therapy, an intervention that replaces circulating sickle red blood cells (RBCs) with donor RBCs. Storage of RBCs makes the intervention logistically feasible. The average storage duration for units transfused at the Duke University Medical Center is approximately 2 weeks, a time window that should anticipate the accumulation of irreversible storage lesion to the RBCs. However, no metabolomics study has been performed to date to investigate the impact of exchange transfusion on recipients' plasma and RBC phenotypes. STUDY DESIGN AND METHODS: Plasma and RBCs were collected from patients with sickle cell anemia before transfusion and within 5 hours after exchange transfusion with up to 11 units, prior to metabolomics analyses. RESULTS: Exchange transfusion significantly decreased plasma levels of markers of systemic hypoxemia like lactate, succinate, sphingosine 1-phosphate, and 2-hydroxyglutarate. These metabolites accumulated in transfused RBCs, suggesting that RBCs may act as scavenger/reservoirs. Transfused RBCs displayed higher glycolysis, total adenylate pools, and 2,3-diphosphoglycerate, consistent with increased capacity to deliver oxygen. Plasma levels of acyl-carnitines and amino acids decreased, while fatty acids and potentially harmful phthalates increased upon exchange transfusion. CONCLUSION: Metabolic phenotypes confirm the benefits of the transfusion therapy in transfusion recipients with SCD and the reversibility of some of the metabolic storage lesion upon transfusion in vivo in 2-week-old RBCs. However, results also suggest that potentially harmful plasticizers are transfused.
BACKGROUND: Exchange transfusion is a mainstay in the treatment of sickle cell anemia. Transfusion recipients with sickle cell disease (SCD) can be transfused over 10 units per therapy, an intervention that replaces circulating sickle red blood cells (RBCs) with donor RBCs. Storage of RBCs makes the intervention logistically feasible. The average storage duration for units transfused at the Duke University Medical Center is approximately 2 weeks, a time window that should anticipate the accumulation of irreversible storage lesion to the RBCs. However, no metabolomics study has been performed to date to investigate the impact of exchange transfusion on recipients' plasma and RBC phenotypes. STUDY DESIGN AND METHODS: Plasma and RBCs were collected from patients with sickle cell anemia before transfusion and within 5 hours after exchange transfusion with up to 11 units, prior to metabolomics analyses. RESULTS: Exchange transfusion significantly decreased plasma levels of markers of systemic hypoxemia like lactate, succinate, sphingosine 1-phosphate, and 2-hydroxyglutarate. These metabolites accumulated in transfused RBCs, suggesting that RBCs may act as scavenger/reservoirs. Transfused RBCs displayed higher glycolysis, total adenylate pools, and 2,3-diphosphoglycerate, consistent with increased capacity to deliver oxygen. Plasma levels of acyl-carnitines and amino acids decreased, while fatty acids and potentially harmful phthalates increased upon exchange transfusion. CONCLUSION: Metabolic phenotypes confirm the benefits of the transfusion therapy in transfusion recipients with SCD and the reversibility of some of the metabolic storage lesion upon transfusion in vivo in 2-week-old RBCs. However, results also suggest that potentially harmful plasticizers are transfused.
Authors: James T Yurkovich; Daniel C Zielinski; Laurence Yang; Giuseppe Paglia; Ottar Rolfsson; Ólafur E Sigurjónsson; Jared T Broddrick; Aarash Bordbar; Kristine Wichuk; Sigurður Brynjólfsson; Sirus Palsson; Sveinn Gudmundsson; Bernhard O Palsson Journal: J Biol Chem Date: 2017-10-13 Impact factor: 5.157
Authors: Sarah Gehrke; Amudan J Srinivasan; Rachel Culp-Hill; Julie A Reisz; Andrea Ansari; Alan Gray; Matthew Landrigan; Ian Welsby; Angelo D'Alessandro Journal: Transfusion Date: 2018-04-24 Impact factor: 3.157
Authors: Tamir Kanias; Derek Sinchar; David Osei-Hwedieh; Jeffrey J Baust; Andrew Jordan; James C Zimring; Hayley R Waterman; Karen S de Wolski; Jason P Acker; Mark T Gladwin Journal: Transfusion Date: 2016-08-09 Impact factor: 3.157
Authors: Andrew M Intlekofer; Raymond G Dematteo; Sriram Venneti; Lydia W S Finley; Chao Lu; Alexander R Judkins; Ariën S Rustenburg; Patrick B Grinaway; John D Chodera; Justin R Cross; Craig B Thompson Journal: Cell Metab Date: 2015-07-23 Impact factor: 31.373
Authors: Reed W Kamyszek; Matthew W Foster; Brooke A Evans; Keaton Stoner; Jessica Poisson; Amudan J Srinivasan; J Will Thompson; M Arthur Moseley; Micah J Mooberry; Ian J Welsby Journal: Blood Transfus Date: 2020-08-06 Impact factor: 3.443
Authors: Ian J Welsby; Philip J Norris; William J Mauermann; Mihai V Podgoreanu; Chelsea M Conn; Laurie Meade; Tamara Cannon; Sheila M Keating; Christopher C Silliman; Marguerite Kehler; Phillip J Schulte; Daryl J Kor Journal: Anesthesiology Date: 2021-03-01 Impact factor: 7.892
Authors: Tiffany Thomas; Francesca Cendali; Xiaoyun Fu; Fabia Gamboni; Evan J Morrison; Jonathan Beirne; Travis Nemkov; Marianna H Antonelou; Anastasios Kriebardis; Ian Welsby; Ariel Hay; Karolina H Dziewulska; Michael P Busch; Steven Kleinman; Paul W Buehler; Steven L Spitalnik; James C Zimring; Angelo D'Alessandro Journal: Transfusion Date: 2021-04-26 Impact factor: 3.337