Abstract:
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. STUDY DESIGN AND 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. CONCLUSION: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.
journal_name
Transfusionjournal_title
Transfusionauthors
Bourgeaux V,Hequet O,Campion Y,Delcambre G,Chevrier AM,Rigal D,Godfrin Ydoi
10.1111/j.1537-2995.2010.02663.xsubject
Has Abstractpub_date
2010-10-01 00:00:00pages
2176-84issue
10eissn
0041-1132issn
1537-2995pii
TRF2663journal_volume
50pub_type
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