WO2002023988A1 - Stockage prolonge de globules rouges - Google Patents

Stockage prolonge de globules rouges Download PDF

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Publication number
WO2002023988A1
WO2002023988A1 PCT/US2000/025712 US0025712W WO0223988A1 WO 2002023988 A1 WO2002023988 A1 WO 2002023988A1 US 0025712 W US0025712 W US 0025712W WO 0223988 A1 WO0223988 A1 WO 0223988A1
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WIPO (PCT)
Prior art keywords
rbcs
suspension
solution
rbc
storage
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PCT/US2000/025712
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English (en)
Inventor
John R. Hess
Tibor J. Greenwalt
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U.S. Army Medical Research And Materiel Command
University Of Cincinnati
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Application filed by U.S. Army Medical Research And Materiel Command, University Of Cincinnati filed Critical U.S. Army Medical Research And Materiel Command
Priority to PCT/US2000/025712 priority Critical patent/WO2002023988A1/fr
Priority to AU2002238218A priority patent/AU2002238218A1/en
Publication of WO2002023988A1 publication Critical patent/WO2002023988A1/fr

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A01N1/0205—Chemical aspects
    • A01N1/021—Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
    • A01N1/0226—Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients

Definitions

  • the invention generally relates to methods and materials associated with the storage of whole blood and red blood cells (RBC).
  • RBC red blood cells
  • RBCs are packed by centrifugation, plasma is removed so that RBCs make up 80% of the volume, and then 100 ml of additive solution is added sterilely.
  • the resulting suspensions have a RBC volume fraction of approximately 55%.
  • RBCs stored in the conventional FDA-approved additive solutions can be stored for only 6 weeks with an acceptable 24-hour in vivo recovery. To increase the time of acceptable in vivo recovery of RBCs in liquid storage, attempts have been made to improve additive solutions and storage processes. In "Studies In Red Blood Cell Preservation-7.
  • the present invention relates to a novel additive solution useful for the storage of human RBCs under refrigerated conditions using an additive solution to preserve RBCs at about 1 to 6°C for up to about 11 weeks or more.
  • Additive solutions and processes in accordance with the present invention allow the viable storage of human RBCs for an extended period of time in a solution which is directly infusible in humans.
  • an object of the present invention to provide an additive solution for storage of human RBCs which solution substantially increases the storage time of the RBCs at about 1 to about 6°C while maintaining an acceptable recovery of the RBCs.
  • the aqueous solution contains adenine, dextrose, Na 2 HPO , mannitol, and at least one physiologically acceptable sodium salt in amounts sufficient to preserve RBCs which amount includes a buffering amount of sodium bicarbonate and or trisodium citrate to maintain the pH at or above about 8, preferably at about 8.4.
  • the additive solutions are useful in a method for storing RBCs, which method include the steps of:
  • RBC suspensions produced in accordance with the invention after about 11 weeks or more of storage provide a sufficiently therapeutic amount of recoverable RBCs and are directly infusible into humans without further processing in accordance with known standards established for transfusion of RBCs.
  • Figure 1 demonstrates the 24 hour in vivo recovery of RBCs stored in a variety of original solutions for periods ranging from 5 to 8 weeks.
  • Figure 2 demonstrates the 24 hour in vivo recovery of RBCs stored in EAS-61, an original additive solution according to the present invention, for periods ranging from 8 to 9 weeks.
  • Figure 3 (A-D) demonstrates the effect of increasing concentrations of sodium bicarbonate on A) RBC ATP content, B) whole blood lactate content, C) extracellular pH, and D) intracellular pH.
  • the individual solutions contain 0 (- ⁇ -), 10 (- ⁇ -), 20 (- A-), and 30 (-•-) mEq/L of sodium bicarbonate.
  • Figure 4 (A-D) demonstrates the effect of increasing concentrations of sodium chloride on A) RBC ATP content, B) extracellular pH, C) whole blood lactate content, and D) hemolysis %.
  • the individual solutions contain 26 (- ⁇ -), 50 (- ⁇ -), 1O0 (- A-), and 150 (-•-) mEq/L of sodium chloride.
  • Figure 5 compare the effects of storage in two different additive solutions at two volumes on A) RBC ATP content, B) extracellular pH, C) whole blood lactate content, D) morphology index and E) hemolysis %.
  • the individual solutions and volumes were AS-3 at 100 mL (-o-), AS-3 at 200 mL (-•-), EAS-61 at
  • Figure 6 shows the percentage recovery for EAS-67 additive after an 11 -week storage.
  • the term “recovery” is used herein to indicate the fraction of stored RBCs that remains in circulation for 24 hours, after re-infusion into the original human donor.
  • the term “prolonged” or “extended” storage is used herein to indicate the preservation or storage of RBCs for a period of time greater than 6 weeks up to about
  • An additive solution in accordance with the invention comprises an aqueous solution of adenine, dextrose, Na 2 HPO , mannitol, and at least one physiologically acceptable sodium salt, in concentrations suitable to preserve RBCs which amount includes the amount of sodium bicarbonate or trisodium citrate which would maintain the pH during storage at levels at or above about 8, preferably at levels about 8.4.
  • the solution contains adenine from about 1 to 3 mM, dextrose from about 20 to 115 mM, Na 2 HP0 from about 4 to 15 mM, mannitol from about 15 to 60 mM, and at least one physiologically acceptable sodium salt from about 20 to 130 mM.
  • adenine is about 2 mM
  • dextrose is about 50 to 110 mM
  • Na 2 HPO 4 is about 9 to 12 mM
  • mannitol is about 20 to 50 mM
  • at least one physiologically acceptable sodium salt is about 25 to 75 mM. This amount would include the 10-30 mM of sodium bicarbonate.
  • a combination of Na 2 HPO , and NaH 2 PO can also be used in lieu of Na 2 HPO 4 , alone.
  • Suitable sodium salts useful in the medium of the invention include those salt compounds containing a sodium cation which are physiologically acceptable in humans.
  • Preferred sodium salts include sodium chloride, sodium acetate, -sodium citrate and the like. Most preferably, the medium contains about 20 to 100 mM of sodium chloride and 0 to 53 mM of sodium acetate. These preferred molar amounts would be lessened by the molar amount of sodium bicarbonate or trisodium citrate present.
  • the pH of the additive solution is maintained in a range of about 7 to 9 at room temperature.
  • the pH of the additive solution of the invention is in the range of about 8 to 8.8.
  • the pH of the additive solution is about
  • the osmolarity of the suspension medium of the invention is in the range of about 200 to 310 mOsm. Preferably, the osmolarity is in the range of about 221 to 280 mOsm. Most preferably, the osmolarity of the additive solution is about 240 to 256 mOsm.
  • RBCs useful in the present invention are those which have been separated from their plasma and resuspended in an anticoagulant solution in the normal course of component manufacture. Briefly stated, a standard whole blood sample (450 ⁇ 45 ml) containing RBCs and plasma is mixed with an anticoagulation solution (about 63 ml) to form a suspension of whole blood. Proportional increases or decreases in solution volumes to reflect different donor blood volumes such as 400 ⁇ 40 ml - 500 ⁇ 50 ml can also be used. The whole blood suspension is thereafter centrifuged to separate the RBCs from the blood plasma thereby forming a packed RBCs. The performance of the overall process is improved by leukocyte reduction using conventional techniques.
  • Suitable anticoagulants include conventional anticoagulants known for storage of RBCs.
  • the anticoagulants include citrate anticoagulants having a pH of
  • CPD 5.5 to 8.0
  • e.g. CPD, half-strength CPD and the like e.g. CPD, half-strength CPD and the like.
  • the most preferred anticoagulant is CPD.
  • additive solution is added to the packed RBC suspension in an amount sufficient to provide a therapeutic effective amount of recoverable RBCs in the cell suspension.
  • the additive solution is added at a volume ranging from about 140 ml to about 400 ml, preferably about 180 to about 300 ml, most preferably about 300 ml.
  • the RBC volume fraction in the cell suspension i.e. after addition-of additive solution, is about 27 to 50% of the total suspension. More preferably, the RBC volume fraction in the cell suspension is about 35 to about 45%. most preferably, the RBC volume fraction in the cell suspension is about 43% of the total suspension.
  • the RBC suspension is then generally stored in standard polyvinyl chloride
  • PNC blood storage bags using either the collection bag or PNC transfer packs of different sizes depending on the volume of the stored aliquot.
  • the RBC suspension is stored at about 1 to 6°C according to standard blood bank procedure as described in Clinical-Practice of Blood Transfusion editors: Petz & S wisher, Churchill-Livingston publishers, ⁇ .Y., 1981. All documents cited herein infra and supra are hereby incorporated by reference thereto.
  • the increased volume of nutrient solution allows an increased mass of substrate to be delivered at acceptable concentrations while providing solute for dilution of metabolic waste products thereby reducing feedback inhibition of glucose metabolism.
  • the additive solutions of the invention can also be used to rehydrate lyophilized RBC or in the thawing of stored frozen blood or blood component, e.g. RBC.
  • Additive solutions in accordance with the present invention were prepared by mixing the components in an aqueous solution.
  • Adenine was obtained from Sigma Chemical (St. Louis, Mo.).
  • the other chemicals used were of USP grade and were obtained from Fisher Scientific (Cincinnati, OH).
  • Sterility of the additive solution was achieved by filtration through a 0.22-um filter with a filling bell (Sterivex-GX, Millipore corporation, Bedford, MA) into a 1-L sterile transfer packs (Baxter Healthcare, IL). Sterility was established by culture.
  • the pH was measured using an Orion pH meter (Model 900A Analytical Technology, Inc., Orion, Boston, MA).
  • the osmolalities were measured by freezing point depression (Osmette TM Precision Systems, Sudbury, MA).
  • Blood Samples Blood donors acceptable by the American Association of Blood Banks and Food and Drug Administration criteria were used. Standard units of blood (450 ml) were collected with 63 ml CPD polyvinyl-chloride bags. Each unit of whole blood was centrifuged and the platelet-rich plasma expressed into a satellite bag. Additive solutions in the stated volume were added and the unit stored at 1-6°C for the stated period.
  • the compositions of the various EAS and AS-3 are compared in Table 2.
  • the EASs were made from high purity adenine, sugars, and salts and sterilely filtered into one-liter storage bags. The bags were held at room temperature for two weeks. The solutions were then cultured and the cultures incubated for another two weeks. When sterility was confirmed by the absence of bacterial growth for 7-14 days, the solutions were aliquoted by weight into 600 mL bags. All connections were made using a sterile connecting device (SCD 312, Termumo Medical Corp. Elkton, MD).
  • Example 1 RBC recovery after storage was measured as the autologous 24-hour recovery fraction.
  • EAS-61 The components of EAS-61 are described in Table 1 below.
  • the pH of the solution at room temperature was 8.58 and the measured total osmolarity was 256 mOsm/Kg H 2 O.
  • Table 1 Composition of EAS-61 additive solution
  • Results indicate that 24-hour in vivo recovery percentage of RBC stored in 200 ml of the additive solution of the invention was over 80% after 7 and 8 weeks of storage. By comparison, percentage RBC recovery in 100 ml of
  • AS-3 after 7 weeks of storage was less than about 70%, and in CPDA-I with no additive solution, less than 80% after only 5 weeks of storage of packed RBCs.
  • Example 3 In this study, units were stored in variants of EAS-64 with increasing sodium bicarbonate concentrations (0, 10, 20, 30 mmoI/L) but a constant total sodium concentration and a constant 300 mL AS volume. See Table 2, Study 1 for the components of the composition.
  • EAS-64 variant units Standard units (450 ⁇ 45 mL) of blood were collected from each donor into 63 mL of CPD anticoagulant in the primary polyvinyl-chloride (PNC) bag of an AS- 1 triple-bag collection set (code 4R-14-36, Baxter Healthcare Corporation, Deerfield, IL). Packed cells were prepared by centrifugation at 5,000 x g for 5 minutes at room temperature followed by the removal of sufficient plasma to achieve a hematocrit of 75-80%.
  • PNC polyvinyl-chloride
  • ABO-matched PRBCs were then pooled in groups of three in 1 L sterile bags (code 4R-20-32, Baxter Healthcare Corporation, Deerfield, IL), mixed thoroughly, and aliquoted into the study units by weight using sterile tubing connection for all the transfers.
  • the study units were produced in 600 mL transfer bags (code 4R-20-23, Baxter Healthcare Corporation, Deerfield, IL) by mixing the PRBC aliquot with 300 mL of the EAS.
  • HGB total hemoglobin
  • WBC counts, and RBC counts were measured with a clinical hematology analyzer (MaxM Coulter Counter, Coulter Electronics, Hialeah, FL).
  • Centrifuged microhematocrits (Clay Adams, Becton-Dickinson, Rutherford, NJ) were performed to prevent osmotic changes in cell volume caused by the isotonic diluent used in the blood analyzer.
  • Mean corpuscular volumes (MCN) were calculated from the spun microhematocrit and the RBC count.
  • RBC ATP and whole blood lactate concentrations were measured in deproteinized supernatants.
  • Whole blood or packed cell aliquots were mixed with cold 12% trichloracetic acid to precipitate blood proteins, centrifuged at 2700 x g for 10 minutes, and the protein free supernatant frozen at -80°C until tested.
  • ATP was assayed enzymatically using a commercially available test kit (Procedure 366-UV, Sigma Diagnostics, St. Louis, MO).
  • Intra- and extracellular pH were measured with a benchtop pH meter (Orion 900A, Orion Research Inc., Boston, MA) at 22°C.
  • Blood pH has a temperature coefficient of -0.015 pH units/°C, so pH measured at 22°C will be about 0.22 pH units higher than pH measured at 37°C.
  • Supernatant potassium, glucose, and inorganic phosphorus testing was sent to an outside laboratory (Health Alliance Laboratories, Cincinnati, OH) (here and in example 5).
  • RBC ATP and phosphate concentrations were measured in deproteinized packed cells and whole blood respectively.
  • Whole blood or packed cell aliquots were mixed with cold 10% trichloroacetic acid to precipitate blood proteins, centrifuged at 2700 x g for 10 minutes, and the protein free supernatant frozen at -80°C until tested.
  • ATP was assayed enzymatically using a commercially available test kit (Procedure 366-UN, Sigma Diagnostics, St. Louis, MO).
  • Inorganic phosphate was measured using a procedure by Boehringer-Mannheim Corp., that involves the formation of ammonium phosphomolybdate (Hitachi 747-200).
  • Blood gases and pH were measured on a blood gas analyzer (Corning 855, Ithaca, ⁇ Y). pH was measured at 37°C. Phosphate, lactate, and glucose were measured on a programmable chemical analyzer (Hitachi 902, Boehringer-Mannheim Corp., Indianapolis, IN).
  • Example 4 In this study, units were stored in variants of EAS-61 with increasing sodium chloride concentrations (26, 50, 100, 150 mmol/L) but at a constant 200 mL AS volume. See Table 2, Study 2 for the components of the composition.
  • EAS-61 variant units Standard units (450 ⁇ 45 mL) of blbod were collected from each donor into 63 mL of CPD anticoagulant in the primary polyvinyl-chloride (PNC) bag of an AS-1 triple-bag collection set (code 4R-14-36, Baxter Healthcare Corporation, Deerfield, IL). Packed cells were prepared by centrifugation at 5,000 x g for 5 minutes at room temperature followed by the removal of sufficient plasma to achieve a hematocrit of 75-80%.
  • PNC primary polyvinyl-chloride
  • ABO-matched PRBCs were then pooled in groups of four in 1 L sterile bags (code 4R-20-32, Baxter Healthcare Corporation, Deerfield, IL), mixed thoroughly, and aliquoted into the study units by weight using sterile tubing connection for all the transfers.
  • the study units were produced in 600 mL transfer bags (code 4R-20-23, Baxter Healthcare Corporation, Deerfield, IL) by mixing the PRBC aliquot with 200 mL of the EAS.
  • the results were expressed as percent hemolysis to compensate for the differences in storage hematocrit and Hgb concentrations between samples.
  • Centrifuged microhematocrits (Clay Adams, Becton-Dickinson, Rutherford, NJ) were performed to prevent osmotic changes in cell volume caused by the isotonic diluent used in the blood analyzer.
  • Mean corpuscular volumes (MCV) were calculated from the spun microhematocrit and the RBC count.
  • RBC ATP and whole blood lactate concentrations were measured in deproteinized supernatants.
  • Whole blood or packed cell aliquots were mixed with cold 12% trichloracetic acid to precipitate blood proteins, centrifuged at 2700 x g for 10 minutes, and the protein free supernatant frozen at -80°C until tested.
  • ATP was assayed enzymatically using a commercially available test kit (Procedure 366-UV, Sigma Diagnostics, St. Louis, MO).
  • EAS-61 variants EAS-61 EAS-71 EAS-72 EAS-73 with increasing 26 mEq 50 mEq 100 mEq 150 mEq NaCl content ofNaCl ofNaCl ofNaCl ofNaCl ofNaCl
  • AS-3 and EAS-61 units Standard units (450 ⁇ 45 mL) of blood were collected from each donor into 63 mL of CP2D anticoagulant in the primary polyvinyl-chloride (PVC) bag of an AS-3 double-bag collection set (code 762-54, Pall Corp, Covina, CA). Packed cells were prepared by centrifugation at 5,000 x g for 5 minutes at room temperature followed by the removal of sufficient plasma to achieve a hematocrit of 75-80%. Four units of identical ABO type were then pooled and realiquoted as described above, and either 100 or 200 mL of AS-3 or 100 or 200 mL of EAS-61 was added.
  • PVC polyvinyl-chloride
  • Blood gases and pH were measured on a blood gas analyzer (Coming 855, Ithaca, NY). pH was measured at 37°C. Phosphate, lactate, and glucose were measured on a programmable chemical analyzer (Hitachi 902, Boehringer-Mannheim Corp., Indianapolis, IN).
  • EAS-61 an alkaline additive solution, caused RBC ATP concentrations to increase during the first three weeks of storage ( Figure 5 A). This increase was less with 100 mL of AS-3 and did not occur with 200 mL of AS-3 ( Figure 5 A). These increased concentrations in RBC ATP were temporally associated with increased supernatant pH ( Figure 5B) and increased lactate production (Figure 5C). After the pHs of the suspending solutions became equivalent at 4 weeks of storage, the rates of lactate production, indicated by the slopes of the lactate concentration plots in Figure 3C, became parallel. However, storage in EAS-61 was associated with better RBC morphology, and 200 mL of this additive was better than 100 mL (Figure 5D). Hemolysis was reduced in EAS-61 compared to AS-3 and the 200 mL volume of each additive solution was better than the 100 mL volume in this regard ( Figure 5E).
  • Example 3 EAS-64, a 300 mL 10-week additive solution, was modified by the substitution of sodium chloride with sodium bicarbonate in amounts of 0, 10, 20 and 30 mMol/L. The addition of this salt of a strong base and weak acid makes the solutions more basic initially. The removal of protons in the carbonic anhydrase reaction and subsequent loss of carbon dioxide by diffusion through the bag keeps the solutions relatively more basic throughout storage (data on supernatant bicarbonate and Pco 2 not shown). Lactic acid was produced continuously during storage but at a decreasing rate with time in all the variants of the solution (Figure 3B).
  • Example 5 EAS-61, a 200 mL 9-week additive solution, was modified by the addition of sodium chloride so that the resulting solutions had final concentrations of 26, 50, 100, and 150 mMol/L.
  • the addition of sodium chloride had no effect on supernatant pH or the rate of lactate formation, but it did abolish cell swelling and led to greater morphologic change, greater loss of membrane microvesicles, and increased overall hemolysis.
  • the RBC ATP contents were less at the end of storage, suggesting that the shape change and membrane loss were energy consuming processes.
  • Example 6 EAS-61 was compared directly with AS-3 at 100 and 200 mL additive volumes.
  • the EAS-61 has higher pH but the AS-3 has a higher phosphate concentration giving it more buffer capacity.
  • Increasing amounts of AS-3 drove the storage solution pH down, reducing lactate production and preventing the initial rise in RBC ATP concentration.
  • the supernatant pH of all the groups was equal and the rate of lactate production became essentially equal.
  • RBCs stored in the hypotonic EAS-61 solution had better morphology and 200 mL was better than 100 mL in this regard. Both solutions showed reduced hemolysis with increasing storage solution volume, but at each volume hemolysis was approximately half in EAS-61 of that observed in AS-3.
  • the experimental additive solutions appear to work to improve storage in several ways.
  • they raise the pH in the storage solution and therefore in the intracellular space.
  • the higher intercellular pH appears to drive glycolysis and therefore ATP synthesis in the early weeks of storage so that the later phase of declining RBC ATP content starts higher and later in the course of storage.
  • relative osmotic hypotonia causes RBC swelling, which in turn improves the morphology and reduces the membrane loss by microvesiculation.
  • the shape change and microvesiculation appear to be energy requiring processes and minimizing them appears to conserve ATP for other uses.
  • increasing the volume of additive solution reduces the hemolysis in all the solutions tested.

Abstract

L'invention concerne de nouvelles solutions d'addition utiles pour le stockage de globules rouges humains dans des conditions de réfrigération. L'invention concerne aussi un procédé d'utilisation de ces solutions d'addition selon un volume approprié pour conserver des globules rouges à une température comprise entre 1 et 6 °C pendant une durée égale ou supérieure à au moins 11 semaines environ. Ces solutions d'addition et les procédés de l'invention permettent de conserver de manière viable des globules rouges humains pendant une durée prolongée dans une solution pouvant être directement perfusée à des êtres humains.
PCT/US2000/025712 2000-09-19 2000-09-19 Stockage prolonge de globules rouges WO2002023988A1 (fr)

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PCT/US2000/025712 WO2002023988A1 (fr) 2000-09-19 2000-09-19 Stockage prolonge de globules rouges
AU2002238218A AU2002238218A1 (en) 2000-09-19 2000-09-19 Prolonged storage of red blood cells

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2172188A1 (fr) * 2008-03-21 2010-04-07 Fenwal, Inc. Solution de stockage de cellule sanguine pour un stockage prolongé
US8709707B2 (en) 2004-02-18 2014-04-29 John R. Hess Compositions substantially free of sodium chloride and methods for the storage of red blood cells
US8835104B2 (en) 2007-12-20 2014-09-16 Fenwal, Inc. Medium and methods for the storage of platelets
US8968992B2 (en) 2008-03-21 2015-03-03 Fenwal, Inc. Red blood cell storage medium for extended storage
EP2887800A4 (fr) * 2012-08-22 2016-07-27 Haemonetics Corp Récipient pour la conservation du sang contenant une composition aqueuse pour la conservation des globules rouges
US9402866B2 (en) 2011-04-07 2016-08-02 Fenwal, Inc. Automated methods and systems for providing platelet concentrates with reduced residual plasma volumes and storage media for such platelet concentrates
US9409128B2 (en) 2009-10-23 2016-08-09 Fenwal, Inc. Methods for storing red blood cell products
EP3979797A4 (fr) * 2019-06-07 2023-06-21 University of Cincinnati Solutions de stockage de globules rouges, additifs, et procédés pour améliorer le stockage de globules rouges à l'aide de pyrophosphates inorganiques

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992008349A1 (fr) * 1990-11-07 1992-05-29 Baxter International Inc. Milieu de stockage de plaquettes de sang
US5250303A (en) * 1989-10-06 1993-10-05 The American National Red Cross Procedure for storing red cells with prolonged maintenance of cellular concentrations of ATP and 2,3 DPG
US5487971A (en) * 1986-03-19 1996-01-30 American National Red Cross Synthetic, plasma-free, transfusible storage medium for red blood cells and platelets
US5690963A (en) * 1995-06-30 1997-11-25 The United States Of America As Represented By The Secretary Of The Navy Freeze dried red blood cells
WO2000011946A2 (fr) * 1998-08-31 2000-03-09 Walter Reed Army Institute Of Research Stockage prolonge de globules rouges

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5487971A (en) * 1986-03-19 1996-01-30 American National Red Cross Synthetic, plasma-free, transfusible storage medium for red blood cells and platelets
US5250303A (en) * 1989-10-06 1993-10-05 The American National Red Cross Procedure for storing red cells with prolonged maintenance of cellular concentrations of ATP and 2,3 DPG
WO1992008349A1 (fr) * 1990-11-07 1992-05-29 Baxter International Inc. Milieu de stockage de plaquettes de sang
US5690963A (en) * 1995-06-30 1997-11-25 The United States Of America As Represented By The Secretary Of The Navy Freeze dried red blood cells
WO2000011946A2 (fr) * 1998-08-31 2000-03-09 Walter Reed Army Institute Of Research Stockage prolonge de globules rouges

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1987, MOORE G L ET AL: "LIQUID STORAGE AT 4 C OF PREVIOUSLY FROZEN RED CELLS", XP002171987, Database accession no. PREV198885034036 *
TRANSFUSION (ARLINGTON), vol. 27, no. 6, 1987, pages 496 - 498, ISSN: 0041-1132 *

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8709707B2 (en) 2004-02-18 2014-04-29 John R. Hess Compositions substantially free of sodium chloride and methods for the storage of red blood cells
US9314014B2 (en) 2004-02-18 2016-04-19 University Of Maryland, Baltimore Compositions and methods for the storage of red blood cells
US8835104B2 (en) 2007-12-20 2014-09-16 Fenwal, Inc. Medium and methods for the storage of platelets
US10358627B2 (en) 2007-12-20 2019-07-23 Fenwal, Inc. Medium and methods for the storage of platelets
EP2172188A1 (fr) * 2008-03-21 2010-04-07 Fenwal, Inc. Solution de stockage de cellule sanguine pour un stockage prolongé
US8871434B2 (en) 2008-03-21 2014-10-28 Fenwal, Inc. Red blood cell storage medium for extended storage
US8968992B2 (en) 2008-03-21 2015-03-03 Fenwal, Inc. Red blood cell storage medium for extended storage
US9943077B2 (en) 2009-10-23 2018-04-17 Fenwal, Inc. Methods for storing red blood cell products
US9409128B2 (en) 2009-10-23 2016-08-09 Fenwal, Inc. Methods for storing red blood cell products
US11864553B2 (en) 2009-10-23 2024-01-09 Fenwal, Inc. Methods and systems for providing red blood cell products with reduced plasma
US9402866B2 (en) 2011-04-07 2016-08-02 Fenwal, Inc. Automated methods and systems for providing platelet concentrates with reduced residual plasma volumes and storage media for such platelet concentrates
US10273456B2 (en) 2011-04-07 2019-04-30 Fenwal, Inc. Automated methods and systems for washing platelet concentrates
EP2887800A4 (fr) * 2012-08-22 2016-07-27 Haemonetics Corp Récipient pour la conservation du sang contenant une composition aqueuse pour la conservation des globules rouges
EP3979797A4 (fr) * 2019-06-07 2023-06-21 University of Cincinnati Solutions de stockage de globules rouges, additifs, et procédés pour améliorer le stockage de globules rouges à l'aide de pyrophosphates inorganiques

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