Anaerobic blood storage and pathogen inactivation method

1. A method for blood pathogen reduction of a blood product comprising:

removing oxygen from a blood product to prepare an oxygen reduced blood product;

reducing blood pathogens from said blood product comprising:

adding amustaline (S-303) to a final concentration of between 0.1 and 0.5 millimolar (mM);

adding glutathione (GSH) to a final concentration of between 2 to 20 mM; and

incubating said oxygen reduced blood product comprising said S-303 and GSH under oxygen reduced conditions for up to 9 hours;

whereby residual pathogens are reduced between 60 and 100%, said S-303 level is reduced to a non-toxic level, and the level of microparticle formation is reduced compared to a blood product treated with S-303 under non-oxygen reduced conditions.

2. The method of claim 1 , further comprising storing said oxygen reduced pathogen reduced blood product under anaerobic conditions.

3. The method of claim 1 , further comprising reducing carbon dioxide from said blood product.

4. The method of claim 1 , wherein said blood product is whole blood, leukoreduced whole blood, plasma, or packed red blood cells.

5. The method of claim 1 , further comprising centrifuging said blood product after said adding S-303 to form packed red blood cells.

6. The method of claim 5 , further comprising mixing said packed red blood cells with an additive solution selected from the group consisting of AS-1, AS-3, AS-5, AS-7, SAGGM, and PAGGSM.

7. A pathogen reduced, oxygen reduced blood product having a concentration of between approximately 0.1 and 0.5 millimolar (mM) S-303, having an oxygen saturation (SO2) of less than 25%, and having a pCO2 of 90 mmHg or less at 37° C.

8. The pathogen reduced, oxygen reduced blood product of claim 7 , further comprising a final concentration of between approximately 2 to 20 mM glutathione (GSH).

9. The pathogen reduced, oxygen reduced blood product of claim 7 , further comprising improvements after storage at 4° C. of at least two parameters selected from the group consisting of complete blood counts (CBC), concentration of residual pathogen, percent hemolysis, adenosine triphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG), deformability, microparticle formation, % SO2, and decomposition kinetics of S-303.

10. The pathogen reduced, oxygen reduced blood product of claim 9 , wherein said blood product is whole blood, leukoreduced whole blood, plasma, or packed red blood cells.

11. The pathogen reduced, oxygen reduced blood product of claim 9 , wherein said adenosine triphosphate (ATP) and said 2,3-diphosphoglycerate (2,3-DPG) are increased by greater than 10% compared to pathogen inactivated oxygenated blood.

12. The pathogen reduced, oxygen reduced blood product of claim 9 , wherein said microparticle formation is reduced by greater than four-fold after at least one week of storage compared to pathogen inactivated oxygenated blood.

13. A method for improving the efficacy of pathogen inactivation of S-303 in a blood product comprising:

removing oxygen from said blood product to prepare an oxygen reduced blood product;

adding amustaline (S-303) to a final concentration of between 0.1 and 0.5 millimolar (mM); and

adding glutathione (GSH) to a final concentration of between 2 to 20 mM;

incubating said oxygen reduced blood product comprising said S-303 and GSH under oxygen reduced conditions for up to 9 hours;

whereby residual pathogens are reduced between 60 and 100% and S-303 level is reduced to a non-toxic level.

14. The method of claim 13 , further comprising reducing carbon dioxide from said blood product.

15. The method of claim 13 , further comprising storing said oxygen reduced pathogen reduced blood product under anaerobic conditions.

16. The method of claim 13 , wherein said blood product is whole blood, leukoreduced whole blood, plasma, or packed red blood cells.

17. The method of claim 1 , wherein said level of microparticle formation is reduced by greater than 10% compared to a blood product treated with S-303 under non-oxygen reduced conditions.

18. The method of claim 1 , wherein said removing oxygen from said blood product and said reducing blood pathogens occur simultaneously.

19. The method of claim 13 , wherein said removing oxygen from said blood product and said adding amustaline (S-303) occur simultaneously.

20. The method of claim 1 , wherein said removing oxygen from said blood product is prior to said reducing blood pathogens.

21. The method of claim 13 , wherein said removing oxygen from said blood product is prior to said adding amustaline (S-303).

22. The method of claim 6 , wherein said additive solution has an acidic pH.

23. The blood product of claim 7 , wherein said pathogen reduced, oxygen reduced oxygen saturation (SO2) is less than 15%.

24. The method of claim 1 , wherein said non-toxic level is less than 10 nM.

25. A pathogen reduced, oxygen reduced blood product having an oxygen saturation (SO2) of less than 25%, having a pCO2 of 90 mmHg or less at 37° C., and having a concentration of S-300 greater than the concentration of amustaline (S-303).

26. The pathogen reduced, oxygen reduced blood product of claim 25 , wherein said S-300 is non-reactant degradant produced from the hydrolysis of S-303.

27. The pathogen reduced, oxygen reduced blood product of claim 25 , wherein said concentration of S-303 is less than 10 nM.

28. The pathogen reduced, oxygen reduced blood product of claim 25 , further comprising a non-toxic level of said S-303.

29. The pathogen reduced, oxygen reduced blood product of claim 25 , wherein said blood product, is whole blood, leukoreduced whole blood, platelets, plasma, or packed red blood cells.

30. The pathogen reduced, oxygen reduced blood product of claim 25 , further comprising a reduction in microparticle formation compared to a blood product treated with S-303 under non-oxygen reduced conditions.