Serum-derived albumin as a cryoprotective agent for the long-term storage of red blood cells: A preliminary examination

BACKGROUND: Cryopreservation extends the shelf life of red blood cells (RBC) from weeks to years, offering major advantages for blood banking logistics, especially in remote environments. However, current glycerol-based methods, though effective, are limited in scope due to complex post-thaw washing and incompatibility with routine clinical workflows. This study evaluated plasma-derived albumin as a potential alternative cryoprotective agent (CPA) for human RBC.

STUDY DESIGN AND METHODS: Donor-derived RBC were suspended in 25% w/v bovine serum albumin (BSA) prepared in various diluents and tested for biocompatibility and cryoprotective efficacy under rapid freezing (immersion in liquid nitrogen) and gradual freezing with storage at -80°C. Post-thaw recovery was quantified by measuring hemolysis after resuscitation of frozen cells to 37°C.

RESULTS: Albumin-based media were non-toxic, maintaining >99% RBC recovery prior to freezing. When rapidly frozen, albumin conferred strong cryoprotection (≥95% recovery) in salt-rich diluents such as SAG-M, Hartmann's, and Alsever's solutions, exceeding that of glycerol-based CPA (77 ± 25%). Albumin's cryopreservative efficacy was enhanced in ionic media of neutral pH but was absent entirely under gradual freezing (<20% recovery).

DISCUSSION: The cryoprotective effect of albumin appears dependent on rapid cooling and ionic co-solutes, suggesting a mechanism rooted in colloid-ion interactions rather than direct inhibition of ice formation. The dependence on freeze rate and ionic environment suggests that multiple solution properties contribute to its efficacy. While further work is required to clarify underlying mechanisms, albumin-based methods may provide a basis for a simplified method of cryopreservation.