The Science

Clinical Implications of The

Storage Lesion

Deterioration of the RBC have been implicated in many transfusion related adverse events, although the direct link between the storage lesion and transfusion side effects is not completely understood. Numerous studies have suggested a linkage to hyper-coagulability, inflammation, impaired perfusion, immuno-modulation, organ dysfunction13 and mortality14.
Notable examples include:

  • Negative clinical outcomes in cardiac surgery when using ‘older’ blood1-3
  • Multiple organ failure in surgical4 or pediatric ICU5, or trauma ICU6 patients associated with advanced age of transfused red cells
  • Increased mortality among trauma patients receiving large transfusion volume when older units are transfused
  • Correlation between older units and increased mortality in severe sepsis7 or pneumonia animal model8
  • Failure to improve O2 utilization attributed to decreased 2,3-DPG and decreased cardiac index associated with increased blood viscosity9-10
  • Increase in post-operative delirium11

This evidence suggests that the ineffectiveness and negative consequences of some transfusions are attributable, at least in part, to the compromising effects of reduced RBC quality. Poor quality of stored blood is attributed to extended storage, and accumulation of toxic substances in the suspending solution of RBC units during storage. But recent randomized, controlled studies have thus far been unable to confirm a significant measurable effect on clinical outcomes. At least in the patient populations studied, the effect was either non-existent or too subtle to detect for the size of the study.

A direct link between RBC storage lesions and the adverse clinical outcomes may be particularly difficult to establish given the wide variability in the clinical vulnerabilities of blood recipients as well as the genetic diversity among blood donors. To get a true test of the clinical impact in patients will likely require identifying a patient population that exhibits a particular vulnerability to an identified storage lesion process and then designing studies to test that specific hypothesis.

Hemorrhagic shock patients, for example, may be particularly vulnerable to the negative consequences of the storage lesion because of their high likelihood of receiving many units of blood during resuscitation, allowing the storage lesion to accumulate in their system.

Of special concern are patients with inherited hemoglobinopathies such as sickle cell disease or thalassemia. People who suffer from these diseases have defective hemoglobin that does not function properly in gas transport, and often have significantly reduced RBC life span. Both populations require a lifetime of regular transfusions of greater than 30 units per year, resulting in long term iron overload, which can lead to morbidity unless the patients undergo continuous iron chelation therapy.12 One of the major sources of excess iron in chronically transfused patients is hemoglobin originating from non-viable RBC destroyed after transfusion.


  1. Koch CG, Li L, Sessler DI, et al. Duration of red-cell storage and complications after cardiac surgery. The New England journal of medicine 2008;358:1229-39.
  2. Sanders J, Patel S, Cooper J, et al. Red blood cell storage is associated with length of stay and renal complications after cardiac surgery. Transfusion 2011;51:2286-94.
  3. Salaria ON, Barodka VM, Hogue CW, et al. Impaired red blood cell deformability after transfusion of stored allogeneic blood but not autologous salvaged blood in cardiac surgery patients. Anesth Analg 2014;118:1179-87.
  4. Zallen G, Offner PJ, Moore EE, et al. Age of transfused blood is an independent risk factor for postinjury multiple organ failure. American journal of surgery 1999;178:570-2.
  5. Karam O, Tucci M, Bateman ST, et al. Association between length of storage of red blood cell units and outcome of critically ill children: a prospective observational study. Critical care (London, England) 2010;14:R57.
  6. Spinella PC, Carroll CL, Staff I, et al. Duration of red blood cell storage is associated with increased incidence of deep vein thrombosis and in hospital mortality in patients with traumatic injuries. Critical care (London, England) 2009;13:R151.
  7. Purdy FR, Tweeddale MG, Merrick PM. Association of mortality with age of blood transfused in septic ICU patients. Can J Anaesth 1997;44:1256-61.
  8. Solomon SB, Wang D, Sun J, et al. Mortality increases after massive exchange transfusion with older stored blood in canines with experimental pneumonia. Blood 2013;121:1663-72.
  9. Shah DM, Gottlieb ME, Rahm RL, et al. Failure of red blood cell transfusion to increase oxygen transport or mixed venous PO2 in injured patients. The Journal of trauma 1982;22:741-6.
  10. Mink RB, Pollack MM. Effect of blood transfusion on oxygen consumption in pediatric septic shock. Critical care medicine 1990;18:1087-91.
  11. Brown CHt, Grega M, Selnes OA, et al. Length of Red Cell Unit Storage and Risk for Delirium After Cardiac Surgery. Anesth Analg 2014.
  12. Shander A, Sazama K. Clinical consequences of iron overload from chronic red blood cell transfusions, its diagnosis, and its management by chelation therapy. Transfusion 2010;50:1144-55.
  13. Yoshida T, Prudent M, D’alessandro A. Red blood cell storage lesion: causes and potential clinical consequences. Blood Transfus 2019; 17 (1): 27-52.
  14. Jones AR, Patel RP, Marques MB, et al. Older Blood Is Associated With Increased Mortality and Adverse Events in Massively Transfused Trauma Patients: Secondary Analysis of the PROPPR Trial. Ann Emerg Med 2019; 73 (6): 650-661.