Association of Crystalloid Fluid Infusion with Altered Red Blood Cell (RBC) Morphology, Intravascular Hemolysis, and Organ Dysfunction in Hematopoietic Stem Cell Transplant Patients

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.