Introduction: Blood transfusion is associated with increased morbidity and mortality in the critically ill. The variables contributing to this pathophysiology are unclear, including when increased susceptibility to infection occurs. In addition, the roles of blood storage duration and allogenicity have not been adequately defined. We hypothesize that innate and adaptive immunity are altered in the recipient almost one week after blood transfusion.

Methods: Female C57Bl/6 mice underwent a 100 µL (8% blood volume) tail vein hemorrhage followed by a 200 µL retro-orbital injection of either 1 day old (DO) syngeneic (SYN) C57Bl/6 packed red blood cells (PRBC), 1 DO allogeneic (ALL) Balb/c PRBC, 21 DO SYN PRBC, 21 DO ALL PRBC, or PBS (n=3-4/group). Whole blood was placed in CPD and Adsol™ preservative solutions, centrifuged and stored at 4°C to create PRBC. Spleens were harvested 6 days post transfusion. T helper cells/CD4+, T effector cells/CD8+, B cells/CD19+ and neutrophils/CD11bLy6G+ were studied using flow cytometry. Data is presented as mean±SEM. Statistics were performed by one-way ANOVA.

Results: Transfusion of 1 DO PRBCs induced significant increases in T effector cells (ALL 21.5±1.4, SYN 23.4±1.0, PBS 16.8±0.1; p=0.03) and B cells (ALL 39.9±3.8, SYN 27.0±1.5, PBS 27.7±0.04; p=0.03), with only ALL PRBCs altering the latter. This is consistent with increased activation of adaptive immunity. Additionally, there was a significant decrease in neutrophils following transfusion of any PRBC genotype (ALL 2.4±0.58, SYN 4±0.18, PBS 8.7±0.9; p= 0.001). Transfusion of 21 DO blood had both similar and differing effects as 1 DO PRBCs on splenic leukocyte populations. B cells expanded while the neutrophil population contracted (ALL 2.4±0.03, SYN 3.2±0.03, PBS 4.2±0.06; p=0.04) with the transfusion of any blood genotype. However, only 21 DO ALL PRBCs decreased the T helper cell population (ALL 10.9±0.6, SYN 15.9±2.2, PBS 17.0±0.9; p=0.05). Although 21 DO PRBC induces multiple changes, these alterations are mostly consistent with the suppression of both adaptive and innate immunity. There were no significant changes in total splenic WBC counts, implying percent differences reflected absolute changes.

Conclusion: Transfusion of PRBC induces late alterations in the recipients’ splenic leukocyte populations. Transfusion of young blood is associated with immune activation, while receiving PRBC that has undergone prolonged storage appears to induce a setting of immune suppression. Allogenicity appears to amplify certain affects, including splenic B cell expansion. Interestingly, any PRBC transfusion is associated with a loss of splenic neutrophils. In conclusion, PRBC transfusion generates WBC changes that may explain why recipients of these products are more susceptible to infection. We believe these alterations are consistent with immune suppression and activation demonstrated by other inflammatory insults such as sepsis.