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Background: Trauma and transfusion can both alter immunity, and while transfusions are common among traumatically injured patients, few studies have examined their combined effects on immunity., Study Design and Methods: We tracked the plasma levels of 41 immunomodulatory proteins in 56 trauma patients from time of injury up to 1 year later. In addition, a murine model was developed to distinguish between the effects of transfusion and underlying injury and blood loss., Results: Thirty-one of the proteins had a significant change over time after traumatic injury, with a mixed early response that was predominantly anti-inflammatory followed by a later increase in proteins involved in wound healing and homeostasis. Results from the murine model revealed similar cytokine responses to humans. In mice, trauma and hemorrhage caused early perturbations in a number of the pro- and anti-inflammatory mediators measured, and transfusion blunted early elevations in interleukin (IL)-6, IL-10, matrix metalloproteinase-9, and interferon-γ. Transfusion caused or exacerbated changes in monocyte chemotactic protein-1, IL-1α, IL-5, IL-15, and soluble E-selectin. Finally, trauma and hemorrhage alone increased CXCL1 and IL-13., Conclusions: This work provides a detailed characterization of the major shift in the immunologic environment in response to trauma and transfusion and clarifies which immune mediators are affected by trauma and hemorrhage and which by transfusion., (© 2012 American Association of Blood Banks.)

Purpose: To determine whether physician specialty influences transfusion threshold in patients with acute severe traumatic brain injury (TBI)., Methods: We surveyed transfusion preferences of chiefs of trauma surgery, chairs of neurosurgery, and surgical and neurosurgical ICU directors at all 187 US Level I trauma centers using a scenario-based, multiple-choice instrument administered by mail. We evaluated the hemoglobin value used as a transfusion threshold for patients with severe acute TBI in several scenarios as well as opinions regarding the rationale for transfusion., Results: The response rate was 58% (312/534). Mean time in practice was 17 +/- 8 years and 65% were board certified in critical care. Neurosurgeons (NS) used a greater mean hemoglobin threshold for transfusion of TBI patients than trauma surgeons (TS) and non-surgeon intensivists (CC) whether the intracranial pressure was normal (8.3 +/- 1.2, 7.5 +/- 1.0, and 7.5 +/- 0.8 g/dL; NS, TS, and CC, respectively, P < 0.001) or elevated (8.9 +/- 1.1, 8.0 +/- 1.1, and 8.4 +/- 1.1 g/dL; NS, TS, and CC, respectively, P < 0.001). All three groups commonly believed that secondary ischemic injury is an important problem following TBI (74, 66, and 63%, P = 0.32), but fewer NS believed that transfusions have important immunodulatory effects (25, 91, and 83%, P < 0.001)., Conclusions: Neurosurgeons prefer more liberal transfusion of TBI patients than TS and CC, suggesting that actual practice may depend largely on which specialist is primarily managing care. The observed clinical equipoise would justify a randomized trial of liberal versus restrictive transfusion strategies in patients with TBI.

Background: Blood transfusion after traumatic injury can result in microchimerism (MC) of donor white cells (WBCs) in the recipient as late as 2 to 3 years postinjury, the longest prospective follow-up to date. The purpose of this study was to determine how long transfusion-associated MC lasts after traumatic injury., Study Design and Methods: A group of US combat veterans who received transfusions who responded to a recruitment notice was retrospectively evaluated. Their blood was sampled, and MC was assessed by quantitative allele-specific polymerase chain reaction detection of differences at the HLA-DR locus or a panel of insertion-deletion polymorphism loci. Results of veterans were compared to those from an age- and gender-matched blood donor control group, from whom WBCs were retrieved from leukoreduction filters., Results: Among 163 combat veterans who received transfusion and 150 control subjects who did not receive transfusions, 16 (9.8%) of the veterans and 1 (0.7%) control subject had evidence of MC (relative risk, 14.7; 95% confidence interval, 2.0-110). The veterans with MC included 3 who served in WWII (7% of subjects from that conflict), 5 in Korea (18%), and 6 in Vietnam (7%)., Conclusions: Transfusion for combat-related injury can result in MC that lasts for 60 years, suggesting that it may involve permanent engraftment. MC is rare among male blood donors who did not receive transfusions, who are probably representative of individuals who have not had postnatal allogeneic exposures.

Microchimerism (MC), defined as the persistence of allogeneic cells at low concentrations, is well documented in transfused trauma patients. We hypothesized that genetic polymorphisms linked to cytokine production could contribute to trauma-induced immune modulation and development of microchimerism after transfusion of trauma patients. We used high-throughput SYBR-green-based genotyping of single nucleotide polymorphisms (SNPs) to characterize 59 transfused trauma patients, with MC (n=30) and without MC (n=29), for 4 functionally significant SNPs: TNF (-308), IL 10 (-1082), IFNG (+874), and TGFB1 (+915). We then compared likelihood for development of MC and the magnitude of immune suppression among subjects with and without these selected immune response SNPs. We identified a significant association between TNF (-308A) SNP and both development of MC and diminished immune responsiveness. Hence predisposing genetic factors may explain, in part, why only a subset of trauma patients develops transfusion-associated microchimerism.

Background: Transfusion of trauma patients can result in long-term survival of donor white blood cells (WBCs) or "transfusion-associated microchimerism" (TA-MC). The aim was to determine whether leukoreduction of blood transfusions, advocated to reduce the immunomodulatory effect of transfusion, decreases the likelihood of developing TA-MC., Study Design and Methods: A subgroup of trauma patients from a randomized trial was examined, evaluating the risk of infection following leukoreduced versus nonleukoreduced blood transfusion. Patients' blood was sampled at least 1 month after hospital discharge, and TA-MC was assessed with quantitative allele-specific polymerase chain reaction detection of differences at the HLA-DR locus or a panel of insertion-deletion polymorphism loci distributed throughout the chromosomal complement. At the time of blood sampling, a scripted interview was used to ascertain symptoms suggestive of chronic graft-versus host disease (cGVHD)., Results: For 67 patients evaluated, the mean age was 43 +/- 17 years and mean Injury Severity Score was 24 +/- 12. Median time from injury to blood sampling for TA-MC was 240 (interquartile range, 116-360) days. Nine of 32 patients (28%) in the nonleukoreduced transfusion group developed TA-MC compared to 13 of 35 patients (37%) in the leukoreduced group (p = 0.43). Subjects with TA-MC were no more likely than subjects without TA-MC to have at least one symptom suggestive of cGVHD (64% vs. 76%, respectively)., Conclusions: TA-MC seems to be a prevalent condition among injured patients at the second of two regional trauma centers evaluated, suggesting that it is a common phenomenon after transfusion in the setting of injury. Although leukoreduction removes greater than 99.9 percent of donor WBCs, it fails to prevent or even substantially reduce the likelihood of developing TA-MC. TA-MC does not appear to be strongly associated with symptoms suggestive of cGVHD several months after transfusion.

Background: Blood transfusion can result in long-term survival of donor leukocyte subpopulations, or microchimerism, in the peripheral blood of injured patients. Neither injury severity nor the number of transfusions is associated with its occurrence. We sought to determine whether changes in general or antigen-specific lymphocyte activation may be associated with the subsequent development of microchimerism., Methods: We evaluated 63 transfused trauma patients, which we compared with 10 non-transfused trauma patients and 10 healthy control subjects. Of the 63 transfused patients, 31 were known to have evidence of microchimerism at hospital discharge with real-time quantitative PCR for non-recipient HLA DR alleles. We assessed lymphocyte response to phytohemagglutinin (PHA) using blood sampled upon arrival to the hospital (before transfusion) and at discharge. We performed one-way mixed leukocyte cultures (MLC) with pre-transfusion recipient specimens to assess recipient lymphocyte response to mitomycin-C treated donor cells and vice versa., Results: Lymphocyte response to PHA in microchimeric transfusion recipients was lower at admission (before transfusion) and discharge than in non-microchimeric recipients. Lymphocytes from microchimeric patients had less response to donor cells than did lymphocytes from non-microchimeric patients. Microchimeric patients also more frequently had diminished lymphocyte response to a single blood donor on MLC., Conclusions: Transfusion-associated microchimerism is correlated with diminished response to mitogen challenge as well as to specific alloantigenic challenges. This microchimerism is predated by diminished lymphocyte response to a specific blood donor in many instances. The blood donor associated with this diminished alloantigenic lymphocyte response may be the source of microchimeric cells present in the recipient.