{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:43:24Z","timestamp":1780447404677,"version":"3.54.1"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The storage of red blood cells (RBCs) is essential for transfusion but leads to storage lesions that compromise RBC quality and increase the risk of transfusion\u2010related adverse effects, including allergic transfusion reactions (ATRs). Understanding storage\u2010induced metabolic change is crucial for enhancing transfusion safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design and Methods<\/jats:title>\n                    <jats:p>We conducted targeted metabolomic profiling of RBC supernatants stored in PAGGS\u2010M over 42\u2009days, collecting 161 weekly samples from 23\u2009units. We analyzed 188 metabolites across six compound classes (hexoses, amino acids, biogenic amines, acylcarnitines, glycerophospholipids, and sphingolipids) along with 20 hematological parameters. Additionally, a mast cell degranulation assay evaluated the impact of these changes on ATR risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Over 100 of the 188 metabolites changed significantly during storage, indicating diverse pathway alterations. Key findings include the accumulation of acylcarnitines and depletion of methionine, with mast cell degranulation significantly increased in supernatants from 42\u2010day\u2010old pRBCs versus fresh units. Notably, methionine depletion coincided with a critical transition phase in storage\u2010associated metabolic aging. In addition, elevated levels of acylcarnitines correlated with increased markers of membrane damage, highlighting potential mechanisms underlying allergic transfusion reactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study highlights the impact of storage\u2010induced metabolic changes in exacerbating transfusion\u2010related complications. Therefore, optimization of additive solutions, such as stabilizing methionine levels during storage, may mitigate storage lesions and improve outcomes. Additionally, the storage\u2010time\u2010related increase in mast cell activation suggests a need for targeted interventions, particularly for patients vulnerable to ATRs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/trf.70070","type":"journal-article","created":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T09:05:32Z","timestamp":1768035932000},"page":"455-467","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Longitudinal metabolomics study of phosphate\u2010adenine\u2010guanosine\u2010glucose\u2010saline\u2010mannitol stored red blood cells"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0868-4059","authenticated-orcid":false,"given":"G\u00fcrkan","family":"Bal","sequence":"first","affiliation":[{"name":"Institute of Allergology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP Immunology and Allergology  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7167-4504","authenticated-orcid":false,"given":"Maia","family":"Dzamashvili","sequence":"additional","affiliation":[{"name":"Klinikum Oldenburg Universit\u00e4tsklinik f\u00fcr Innere Medizin \u2010 H\u00e4matologie und Onkologie  Oldenburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1523-6871","authenticated-orcid":false,"given":"Zhuoran","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Allergology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP Immunology and Allergology  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4500-7615","authenticated-orcid":false,"given":"Magda","family":"Babina","sequence":"additional","affiliation":[{"name":"Institute of Allergology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP Immunology and Allergology  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0009-4687","authenticated-orcid":false,"given":"Nidal","family":"Toman","sequence":"additional","affiliation":[{"name":"Department of Psychology Touro University Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulgabar","family":"Salama","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin Humboldt\u2010Universit\u00e4t zu Berlin and Berlin Institute of Health  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.01076"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2010.02926.x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4867"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.9.3521"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/voxs.12222"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708160104"},{"issue":"1","key":"e_1_2_12_8_1","first-page":"27","article-title":"Red blood cell storage lesion: causes and potential clinical consequences","volume":"17","author":"Yoshida T","year":"2019","journal-title":"Blood Transfus"},{"issue":"2","key":"e_1_2_12_9_1","first-page":"197","article-title":"Survival of the fittest? 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