Inositol hexaphosphate-loaded red blood cells prevent in vitro sickling.
BACKGROUND
Hypoxia is a major cause of painful vaso-occlusive crisis in sickle cell disease (SCD). Simple transfusion and red blood cell (RBC) exchange are commonly used as preventive therapies whose aim is to dilute hemoglobin (Hb)S-containing RBCs (SS-RBCs) with normal RBCs (AA-RBCs) to prevent sickling. We hypothesized that the effectiveness of transfusion could be improved by the encapsulation of inositol hexaphosphate (IHP), an allosteric Hb effector, in transfused AA-RBCs. Indeed, apart from their diluting effect on SS-RBCs, IHP-loaded RBCs (IHP-RBCs) with increased oxygen release capacity could palliate in vivo oxygen deprivation and reduce sickling.


METHODS
The study was designed to investigate the therapeutic effect of IHP-RBCs transfusion on in vitro sickling of SS-RBCs collected from 20 SCD patients. Patients' RBCs were diluted with various proportions of IHP-RBCs or AA-RBCs (processed or stored RBCs as controls). Resulting suspensions were subjected to deoxygenation followed by partial reoxygenation at 5% oxygen. Sickling was evaluated by microscopy.


RESULTS
Stored RBCs (50% dose) used to mimic simple transfusion exhibited a poor antisickling effect (5.6%) and a low response rate (65%). In contrast, IHP-RBCs treatment was seven times more effective resulting in 35% of sickling reduction and a 94% response rate. Sickling was inhibited in a dose-dependent manner: 9.9, 25.1, and 35.0% for IHP-RBCs in percentages of 10, 30, and 50%, respectively.


CONCLUSIONS
Our results indicate that IHP-RBCs prevent in vitro sickling and suggest that it could improve conventional transfusion therapy in terms of transfused volume, frequency, and efficacy.
Bourgeaux
Vanessa
V
ERYtech Pharma and EFS Rhône Alpes, Lyon, France.
Hequet
Olivier
O
Campion
Yannick
Y
Delcambre
Gaëlle
G
Chevrier
Anne-Marie
AM
Rigal
Dominique
D
Godfrin
Yann
Y
D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000628:therapy*; D004912:Erythrocytes / Q000737:chemistry* / Q000166:cytology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010833:Phytic Acid / Q000737:chemistry* / Q000627:therapeutic use; D055815:Young Adult
D010833:Phytic Acid