Highlights
- •Unbalanced crystalloids (e.g., NS) are commonly used in HSCT.
- •Crystalloids may be associated with hemolysis and immune dysfunction.
- •Markers of hemolysis significantly changed pre- to post-crystalloid infusion.
- •Crystalloid volume was associated with greater hemolysis and endothelial damage.
- •Alternatives like buffered solutions may be considered in the HSCT population.
Abstract
Endothelial cell activation and injury is common after hematopoietic stem cell transplant
(HSCT) and is associated with many post-transplant complications. An underexplored
mechanism of endothelial cell damage in this population is the infusion of normal
saline (NS, 0.9 % sodium chloride) and other crystalloids, as NS use is associated
with adverse outcomes in other patient populations. We hypothesized that the infusion
of unbalanced crystalloids during HSCT may lead to changes in biomarkers commonly
associated with red blood cell (RBC) hemolysis in patients before and after infusion,
and that markers of endothelial and end-organ damage during admission may be associated
with markers of hemolysis and total crystalloid use. Samples were collected from 97
patients. From pre-fluid infusion to post-fluid infusion, mean haptoglobin decreased
(11.7 ug/ml vs 8.4 ug/ml; p < 0.0001), hemopexin decreased (549 vs 512 μg/ml; p = 0.005),
and red cell distribution width (RDW) decreased (15.7 vs 15.6; p = 0.0009). During
admission (mean 19.4 days, SD 9.9), all markers of tissue and organ damage, including
mean creatinine, lactate dehydrogenase (LDH), blood urea nitrogen (BUN), total bilirubin,
AST, and ALT, increased from admission to peak levels (p < 0.0001). On linear regression,
fluid volume (ml/kg) of crystalloid infusion positively predicted post-fluid infusion
cell-free hemoglobin (r(96) = 0.34, p < 0.0001), free heme (r(96) = 0.36, p < 0.0001),
and peak LDH during admission (r(75) = 0.23, p = 0.041), and negatively predicted
post-fluid infusion hemopexin (r(96) = − 0.34, p < 0.0001). Unbalanced crystalloids
may contribute to hemolysis and endothelial damage in HSCT patients. Alternatives
such as buffered crystalloid solutions (PlasmaLyte, Lactated Ringer’s) may be worth
investigating in this population.
Keywords
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Article info
Publication history
Published online: January 12, 2023
Accepted:
January 12,
2023
Received in revised form:
December 11,
2022
Received:
June 6,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Ltd. All rights reserved.