Risks associated with red blood cell transfusions: potential benefits from application of pathogen inactivation

Kleinman, Steve; Stassinopoulos, Adonis

Transfusion-associated graft-versus-host disease (TA-GVHD), an almost uniformly fatal condition, is prevented by completely inactivating T lymphocytes in RBCs or LR-RBCs. 67 This is currently accomplished by gamma irradiation, which although highly effective in preventing GVHD, has multiple limitations. 68 Rare TA-GVHD cases are still reported likely due to substandard treatment or failure to apply the procedure uniformly to all cellular units for patients at risk, due either to inappropriate institutional criteria or to incorrect patient diagnosis. [68] [69] [70] [71] [72] [73] [74] Gamma irradiation is known to damage RBC membranes causing acute and delayed hemolysis and to damage the Na-K pump resulting in potassium leakage from the RBCs. 75 Consequently, storage of irradiated RBCs is limited to 28 days postirradiation. 76 In the United States in 2011, an estimated 13.4% of transfused RBCs were irradiated. 2 It is likely that the criteria for irradiation varied among institutions. Similarly, the length of time that an irradiated RBC unit is stored before being transfused may also vary. In the scenario of batch mode irradiation with subsequent storage of units, there is the theoretical concern that these RBC units may function less optimally than nonirradiated RBCs and therefore should not be given to patients not at risk of TA-GVHD. The alternative scenario of irradiating units just before product issue poses logistic challenges and is only possible if the institution has its own blood irradiator. Finally, facilities with irradiators have been subject to increasing regulatory scrutiny due to bioterrorism concerns, making the continued use of this equipment less desirable and more expensive. 76 PI-RBCs and PI-WB procedures have been found effective in inactivating white blood cells (WBCs) and T cells and when applied routinely, could replace the use of gamma irradiation, and solve logistic challenges. 77, 78 Data for one of these technologies indicate that PI-RBCs show lower hemolysis, lack of effect on the Na-K pump, and lower extracellular potassium and protein levels, resulting in better in vitro function than gamma-irradiated RBCs. 79