Individual Variability in Response to a Single Sickling Event for Normal, Sickle Cell and Sickle-Trait Erythrocytes

• Published in: Translational research : the journal of laboratory and clinical medicine 2017-03, Vol.181, p.96-107
• Main Authors: Tarasev, M, Muchnik, M, Light, L, Alfano, K, Chakraborty, S
• Format: Article
• Language: English
• Subjects: Adult; Anemia, Sickle Cell - pathology; Area Under Curve; Cell Hypoxia; Erythrocytes - pathology; Female; Humans; Internal Medicine; Male; Sickle Cell Trait - pathology
• ISSN: 1931-5244; 1878-1810
• DOI: 10.1016/j.trsl.2016.09.005

Abstract Hemoglobin S polymerization is the primary event in sickle cell disease, causing irreversible damage to Red Blood Cell (RBC) membranes over repeated polymerization cycles. A single polymerization triggered by a hypoxic environment was reported to result in reversibly (upon re-oxygenation) decreased RBC deformability and increased mechanical fragility (MF). Individualized responses had not been reported, although RBC fragility can vary significantly even among healthy individuals. This study evaluates individual variability in response to a single hypoxia-induced sickling event, through changes in RBC MF. Blood was drawn from 10 normal (AA), 11 sickle cell (SS), and 7 sickle trait (AS) subjects – with hemoglobin S fraction, osmotic fragility, and medical history also collected. Mechanical stress was applied using a bead mill at 50Hz oscillation for 0.5 to 30 minutes. MF profiles here give percent hemolysis upon successive durations of stressing. MF was measured for AA, SS, and AS cells – each equilibrated i) with air, ii) with nitrogen in an anaerobic chamber, and iii) with air after the hypoxic event. While AA subjects exhibited significantly different changes in fragility upon hypoxia, in all cases there was recovery to close to the initial MF values upon re-oxygenation. For AS subjects, recovery at re-oxygenation was observed only in about half of the cases. Fragility of SS cells increased in hypoxia and decreased with re-oxygenation, with significantly variable magnitude of recovery. The variability of response for individual AS and SS subjects indicates that some are potentially at higher risk of irreversible hypoxia-induced membrane damage.