Compositions and methods for the storage of red blood cells
AssigneesUniversity of Maryland, Baltimore, University of Cincinnati
InventorsJohn Hess, Tibor Greenwalt
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Abstract
The present invention provides an aqueous composition for storage of red blood cells consisting essentially of: adenine; dextrose; at least one non-metabolizable membrane-protectant sugar; and a specifically defined pH buffering system. Also provided are improved methods for preserving red blood cells and methods for increasing the viability, membrane retention, and recoverability while suppressing apoptosis, hemolysis, and post-reinfusion clearance of stored red blood cells which utilize the novel compositions.
Claims52
An aqueous composition for storage of red blood cells at about 1 to about 6° C., the composition consisting essentially of:
- adenine;
- dextrose;
- at least one non-metabolizable membrane-protectant sugar;
- and
- a pH buffering system,
- wherein the pH buffering system comprises a combination of physiologically acceptable buffering agents including at least one agent providing bicarbonate anions, at least one agent providing phosphate anions, and at least one agent providing sodium cations, wherein the pH buffering system is present in an amount sufficient for the composition to be operable to maintain a pH of a red blood cell (RBC) suspension to which the composition is added at a value sufficient to establish and maintain during a storage period a reaction equilibrium in the red blood cell that favors glycolysis over synthesis of 2,3-diphosphoglycerate (DPG) from 1,3-DPG, thereby generating a net gain in adenosine tri phosphate (ATP) synthesis with respect to the reaction equilibrium during the storage period.
An aqueous composition for storage of red blood cells at about 1 to about 6° C., the composition comprising:
- adenine;
- dextrose;
- at least one non-metabolizable membrane-protectant sugar;
- and
- a pH buffering system,
- wherein the pH buffering system comprises a combination of physiologically acceptable buffering agents including at least one agent providing bicarbonate anions, at least one agent providing phosphate anions, and at least one agent providing sodium cations, wherein the pH buffering system is present in an amount sufficient for the composition to be operable to maintain a pH of a red blood cell (RBC) suspension to which the composition is added at a value sufficient to establish and maintain during a storage period a reaction equilibrium in the red blood cell that favors glycolysis over synthesis of 2,3-diphosphoglycerate (DPG) from 1,3-DPG, thereby generating a net gain in adenosine tri phosphate (ATP) with respect to the reaction equilibrium during the storage period, and, wherein the composition is substantially free of exogenously derived chloride ions.
A method of preserving red blood cells (RBCs) for a storage period comprising:
- (a) mixing a sample of collected whole blood containing the RBCs to be stored and plasma with an anticoagulant solution, thereby forming a suspension of collected whole blood;
- (b) treating the suspension of collected whole blood to deplete the plasma and concentrate the RBCs, thereby forming packed RBCs;
- (c) mixing the packed RBCs with an amount of an aqueous composition sufficient to form a suspension of RBCs having about 35% to about 70% RBCs by volume;
- (d) cooling the suspension of RBCs to about I to about 6° C.;
- and
- (e) storing the cooled suspension of RBCs according to standard bank procedures,
- wherein the aqueous composition consists essentially of:
- adenine;
- dextrose;
- at least one non-metabolizable membrane-protectant sugar;
- and
- a pH buffering system,
- wherein the pH buffering system comprises a combination of physiologically acceptable buffering agents including at least one agent providing bicarbonate anions, at least one agent providing phosphate anions, and at least one agent providing sodium cations, wherein the pH buffering system is present in an amount sufficient for the composition to be operable to maintain a pH of a red blood cell (RBC) suspension to which the composition is added at a value sufficient to establish and maintain during a storage period a reaction equilibrium in the red blood cell that favors glycolysis over synthesis of 2,3-diphosphoglycerate (DPG) from 1,3-DPG, thereby generating a net gain in adenosine tri phosphate (ATP) synthesis with respect to the reaction equilibrium during the storage period.
Dependencies are inferred from the claim text.