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 dysfunction and mortality.
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 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 therapy12. One of the major sources of excess iron in chronically transfused patients is hemoglobin originating from non-viable RBC destroyed after transfusion.