Deleterious Clinical Effects of Allogeneic Blood Transfusion–Related Immunomodulation

Abstract

The debate about the existence of deleterious clinical effects of allogeneic blood transfusion (ABT)-related immunomodulation (TRIM) continues and is now concentrated on differing interpretations of findings of randomized controlled trials (RCTs). This review focuses on the results of studies reported during the last 5 years, especially recent RCTs, studies of the association of ABT with all-cause mortality, studies of the hypothesis attributing TRIM effects to WBC-derived soluble mediators that accumulate during storage, and studies comparing the risk of adverse outcomes before and after the implementation of WBC reduction of cellular blood components. When this literature is considered along with that available before 2001, the results from studies of adverse clinical TRIM effects remain contradictory. Based on the totality of the evidence, there seems to be an association between WBC-containing ABT and short-term (≤3 months posttransfusion) mortality that becomes manifest in cardiac surgery and in comparison with administration of allogeneic blood components filtered before storage. However, with the possible exception of cardiac surgery, there is no area in the extensive TRIM literature in which there is agreement among the studies or in which the observed clinical effects follow consistently from a postulated biologic mechanism. Allogeneic blood transfusion (ABT) results in the infusion into the recipient of large amounts of foreign antigens in soluble and cell-associated forms. The persistence of these antigens in the circulation of the recipient may create conditions that allow for the development of immune down-regulation. Evidence from a variety of sources indicates that ABT enhances the survival of renal allografts 1 and may increase the recurrence rate of resected malignant neoplasms 2 and the incidence of postoperative bacterial infections, 3-8 as well as reduce the recurrence rate of Crohn disease 9 and/or activate infections with cytomegalovirus or HIV. 10 This syndrome, the mechanisms and clinical relevance of which remain to be defined, has been referred to in the transfusion medicine literature as ABT-related immunomodulation (TRIM). 11,12