Effect of Leukoreduction in Infection Risk in Trauma

Many severely injured patients survive their initial resuscitation only to suffer the late sequelae of nosocomial infection and multiple organ failure. The depth of hemorrhagic shock and the severity of anatomic injury are clearly associated with these adverse outcomes, however there is clear evidence to suggest that events during the resuscitation phase also play an important role in the pathogenesis of these sequelae. Specifically, there is now substantial clinical and experimental evidence implicating blood transfusion and the transfusion of allogeneic passenger leukocytes in the immune dysregulation characteristic of the post-injury state. This immune dysregulation manifests on two fronts: an uncontrolled inflammatory response leading to organ dysfunction and a state of immunoparalysis, leading to the development of nosocomial infection. Allogeneic passenger leukocytes have been implicated in the alterations in non-specific and specific immunity that underlie this state of altered immunoresponsiveness. The importance of allogeneic leukocytes in these phenomena suggests that strategies designed to limit the exposure of patients to these cells may reduce the incidence of post-injury sequelae. Pre-storage leukoreduction, whereby donated blood is passed through a leukocyte filter prior to storage and ultimate transfusion is one such strategy. This strategy remains at the center of a national debate on a policy of universal leukoreduction in which its efficacy is unproven and its cost undisputed.

Study Objectives:

• To evaluate whether there are clinically relevant differences in the rates of infection and in the severity of multiple organ failure in critically injured trauma patients receiving leukoreduced blood products compared to those receiving standard allogeneic blood products.
• To assess T-cell responsiveness and the dominant CD4 lymphocyte subset as measured by T-lymphocyte IL-2 receptor expression and cytokine profile, respectively, in critically injured subjects transfused with leukoreduced blood products compared to subjects receiving standard allogeneic blood products.
• To assess the activational state of the peripheral blood monocyte and the neutrophil in critically injured trauma patients receiving leukoreduced blood products compared to subjects receiving standard allogeneic blood products.
• To evaluate whether there are clinically relevant differences in rates of acute lung injury (ALI) and circulating markers of ALI in patients receiving leukoreduced versus standard allogeneic blood products.
• To evaluate rates of microchimerism in those receiving leukoreduced versus standard allogeneic transfusion