Compositions and methods for the storage of red blood cells

Abstract

The present invention provides an aqueous composition for storage of red blood cells consisting essentially of: adenine; dextrose; at least one nonmetabolizable 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.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional of and, pursuant to 35 U.S.C. §120, claims the benefit of U.S. patent application Ser. No. 11 / 060,026, filed on Feb. 17, 2005, which is pending as of the filing date of this application. Application Ser. No. 11 / 060,026, pursuant to 35 U.S.C. §119(e)(1), claimed priority from Provisional Application Ser. No. 60 / 545,582, filed on Feb. 18, 2004 under 35 U.S.C. §111(b). Both application Ser. No. 11 / 060,026 and Provisional Application Ser. No. 60 / 545,582 are hereby incorporated by reference in their entireties.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]Portions of this work were performed under U.S. Army contract DAMD 17-95-C-5029 and the U.S. government may have an ownership interest herein.BACKGROUND OF THE INVENTION[0003]The invention generally relates to compositions and methods associated with the storage of red blood cells (RBCs). In particular, it relates to an improved RBC stor...

AI Technical Summary

Benefits of technology

The present invention provides novel compositions for storing and preserving red blood cells. By eliminating sodium chloride from the compositions, the inventors discovered that the compositions have an increased capacity for a pH buffering system, which improves the integrity and physiological functioning quality of the stored red blood cells. The compositions retain their superior performance at conventional volumes, making them particularly suitable for storing red blood cells which may be targeted for infusion into multiply or massively transfused patients. The inventive compositions are also operable to maintain the pH of the red blood cell during storage, which helps to maintain the quality of the stored cells for a longer period of time. The inventive compositions and methods of using them provide a storage period for red blood cells throughout which a sufficient therapeutic amount of the cells is recoverable and are directly infusible into patients without further processing.

Problems solved by technology

Such preservation is scientifically tricky and the steps to achieving longer storage duration and higher quality re-infused red blood cells have been incremental.

This, however, led to a reduction in the percent recovery of the resulting “packed RBC.”

Red blood cells (RBCs) stored in these solutions, however, undergo steady deterioration after about 6 weeks as determined by the inability of 75% of such cells to survive in the circulation for 24 hours after re-infusion back into the human donor.

Each of the U.S.-licensed ASs meet the licensure requirements for 6-week RBC storage, but fail to achieve 7-week storage.

However, packed RBCs stored in EAS-2 were not directly infusible but required the removal of the supernatant with a washing step prior to transfusion due to the presence of ammonium in the additive solution.

However, the resulting RBC units contained about 1 percent glycerol and thus, are not safe for transfusion in humans in large amounts.

However, such stored RBC suspensions were not acceptable for direct infusion due to their high content of potassium and ammonia and their low volume fraction of RBCs.

Although these EASs yielded superior performance results, they contained sodium chloride and were formulated to require a relatively large volume resulting in greater dilution of the stored RBC, thus increasing the risk of hemodilution in multiply transfused patient recipients.

In addition, the presence of sodium chloride created a solubility limit on the amount of buffering salts and phosphates that the system could sustain at desirable volumes.

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