157 - Quantifying Neonatal and Infant Cumulative-Longitudinal Exposure to RBC Storage Solution Constituents in a Multi-Institutional Cohort

Publication Number: 2151.157

Thomas C. Binns, Yale School of Medicine, New Haven, CT, United States; Cassandra D. Josephson, Johns Hopkins University School of Medicine, Treasure Island, FL, United States; Rebecca J. Birch, Westat, Rockville, MD, United States; Elaine A. Yu, Vitalant Research Institute, UCSF, San Francisco, CA, United States; John Manis, Boston Children's Hospital, Boston, MA, United States; Daniel W.. Bougie, Versiti, Milwaukee, WI, United States; Elizabeth A. K.. Rowley, Westat - Rockville, MD, Rockville, MD, United States; Ruchika Goel, Southern Illinois University School of Medicine, Springfield, IL, United States; Gisela Marrero-Rivera, UCSF, San Francisco, CA, CA, United States; Ravi M. Patel, Children's Healthcare of Atlanta and Emory University, Atlanta, GA, United States; Brian Custer, Vitalant Research Institute, San Francisco, CA, United States; Paul M. Ness, Johns Hopkins Medical Institutions, Round Pond, ME, United States; Jerome L.. Gottschall, Versiti. Inc., Fox Point, WI, United States; Naomi L.C.. Luban, Children's National Research Institute, Washington, DC, United States; Rowena C. Punzalan, Medical College of Wisconsin and Versiti Wisconsin, Milwaukee, WI, United States; Alexandra Jimenez, Weill Cornell Medicine, new york, NY, United States

Background: Donor red blood cells (RBCs) are stored in solutions varying in compositions of citrate, adenine, glucose, and mannitol. At standard transfusion (TX) doses (≤20 mL/kg), these constituents are considered low risk, but data on the risk of larger-volume or repeated TXs (>20 mL/kg) in neonates and infants are scarce. Evidence is limited to small, single-center studies. With CPDA-1 units scheduled for discontinuation by 2027 and increased reliance on additive solutions anticipated, real-world neonatal exposure data are needed.

Objective: To quantify neonatal and infant exposure to RBC storage solution constituents and evaluate cumulative exposures relative to published theoretical toxicity thresholds.

Design/Methods: We conducted a retrospective, multi-institutional study using the REDS-IV-P Vein-to-Vein database, examining RBC product and recipient data from April 2019 - March 2024. Patients were stratified by birthweight and followed up to 4 months of age. Those on ECMO, CPB, or CVVH were excluded in light of unreliable product modification information. We analyzed TX trends to identify cumulative exposures to storage solutions and their constituents and compared calculated dose rates with published toxicity thresholds.

Results: Among 5,013 infants with 14,669 TXs at 10 hospitals, >80% received RBCs from one storage solution (Fig. 1). Solution type distribution differed by site (p <.0001) and birthweight cohort (p <.0001). Very low birth-weight (VLBW, < 1500 g) infants were more likely to receive mannitol-containing AS-1 (68% of TXs) than other cohorts (24-38%, p<.0001). Among multiply-transfused infants (56%), median (IQR) time to next TX was 3.3 (0.7-9.3) days, while 29% received ≥1 TX within 24 h of another, increasing cumulative exposure risk. Exposures above theoretical toxicities were rare across all TXs for mannitol (0.05%, 6 of 12,000 daily-binned exposures) and adenine (0.10%, 14 of 14,669 aliquot exposures) but occurred more often for citrate (4.74%, 689 of 14,543 hourly-binned exposures) and glucose (7.70%, 1,120 of 14,543 hourly-binned exposures), particularly with large-volume TXs (>40 mL/kg; see Table 1 for percentages stratified by birthweight cohort and TX dose).

Conclusion(s): Although mannitol and adenine exposures above theoretical toxicity thresholds were uncommon, citrate and glucose exposures more often exceeded thresholds in neonates and infants receiving large-volume or closely spaced TXs. These findings underscore the need for awareness of these exposures given limited safety data and support ongoing studies examining their relationship to clinical outcomes.

Figure 1
RBC storage solution exposure by cohort.

Table 1
Percent of transfusion exposures (summed over the unit of time in each constituent's theoretical toxicity threshold rate, left column), stratified by birthweight cohort and transfusion dose, exceeding theoretical toxicity threshold rates (reported in Luban et al., Transfusion, 1991). Of note, these values differ from overall transfusion percentages shown in the text as they represent stratified data.