Severely injured patients often require transfusions of allogeneic blood products to restore intravascular blood volume. Many of these patients survive their initial resuscitation only to experience the late sequelae of nosocomial infection and multiple organ failure. Several lines of clinical and experimental evidence suggest that residual leukocytes present in allogeneic blood products have immunomodulatory effects. These effects might underlie the propensity of trauma patients to develop infection or organ failure. Strategies designed to limit the exposure of patients to allogeneic leukocytes may reduce the incidence of these post-injury sequelae. Pre-storage leukoreduction, a process leading to a 3 log order reduction in passenger leukocytes, represents one such strategy. We postulate that the leukoreduction of blood products will reduce the incidence of nosocomial infections and multiple organ failure in critically injured trauma patients requiring blood transfusion. This proposal seeks to accomplish the following:
Specific aim 1 : To evaluate whether there are differences in the rates of infection and in the severity of organ dysfunction in trauma patients receiving leukoreduced blood products compared to similar patients receiving standard allogeneic blood products.
Specific aim 2 a: To assess T-cell responsiveness and the dominant CD4 lymphocyte subset in trauma patients transfused with leukoreduced blood products compared to subjects receiving standard allogeneic blood products.
Specific aim 2 b: To assess the activational state of the monocyte and the neutrophil in trauma patients receiving leukoreduced blood products compared to those receiving standard allogeneic blood products. Given the large proportion of the United States' blood supply used for emergency transfusions and the risk of sequelae in this high risk population, the results of these studies may provide efficacy data to guide decisions regarding the processing of blood products and provide insight into the mechanisms of transfusion induced immunomodulation.
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