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Inositol hexaphosphate-loaded red blood cells prevent in vitro sickling.
Transfusion. 2010 Oct; 50(10):2176-84.T

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.

Authors+Show Affiliations

ERYtech Pharma and EFS Rhône Alpes, Lyon, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20456710

Citation

Bourgeaux, Vanessa, et al. "Inositol Hexaphosphate-loaded Red Blood Cells Prevent in Vitro Sickling." Transfusion, vol. 50, no. 10, 2010, pp. 2176-84.
Bourgeaux V, Hequet O, Campion Y, et al. Inositol hexaphosphate-loaded red blood cells prevent in vitro sickling. Transfusion. 2010;50(10):2176-84.
Bourgeaux, V., Hequet, O., Campion, Y., Delcambre, G., Chevrier, A. M., Rigal, D., & Godfrin, Y. (2010). Inositol hexaphosphate-loaded red blood cells prevent in vitro sickling. Transfusion, 50(10), 2176-84. https://doi.org/10.1111/j.1537-2995.2010.02663.x
Bourgeaux V, et al. Inositol Hexaphosphate-loaded Red Blood Cells Prevent in Vitro Sickling. Transfusion. 2010;50(10):2176-84. PubMed PMID: 20456710.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inositol hexaphosphate-loaded red blood cells prevent in vitro sickling. AU - Bourgeaux,Vanessa, AU - Hequet,Olivier, AU - Campion,Yannick, AU - Delcambre,Gaëlle, AU - Chevrier,Anne-Marie, AU - Rigal,Dominique, AU - Godfrin,Yann, Y1 - 2010/10/04/ PY - 2010/5/12/entrez PY - 2010/5/12/pubmed PY - 2010/12/14/medline SP - 2176 EP - 84 JF - Transfusion JO - Transfusion VL - 50 IS - 10 N2 - 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. SN - 1537-2995 UR - https://www.unboundmedicine.com/medline/citation/20456710/Inositol_hexaphosphate_loaded_red_blood_cells_prevent_in_vitro_sickling_ L2 - https://doi.org/10.1111/j.1537-2995.2010.02663.x DB - PRIME DP - Unbound Medicine ER -