Lack of persistent microchimerism in contemporary transfused trauma patients.

BACKGROUND: Following transfusion, donor white blood cells (WBCs) can persist long-term in the recipient, a phenomenon termed transfusion-associated microchimerism (TA-MC). Prior studies suggest TA-MC is limited to transfusion following traumatic injury, and is not prevented by leukoreduction. STUDY DESIGN AND METHODS: We conducted a prospective cohort study at a major trauma center to evaluate TA-MC following injury. Index samples were collected upon arrival, prior to transfusion. Follow-up samples were collected at intervals up to one year, and beyond for those testing positive for TA-MC. TA-MC was detected by real-time quantitative allele-specific polymerase chain reaction assays at the HLA-DR locus and several polymorphic insertion deletion sites screening for non-recipient alleles. RESULTS: A total of 378 trauma patients were enrolled (324 transfused cases and 54 non-transfused controls). Mean age was 42 ± 18 years, 74% were male, and 80% were injured by blunt mechanism. Mean Injury Severity Score was 20 ± 12. Among transfused patients, the median (interquartile range) number of red cell units transfused was 6 (3,12), and median time to first transfusion was 9 (0.8,45) hours. Only one case of long-term TA-MC was confirmed in our cohort. We detected short-term TA-MC in 6.5% of transfused subjects and 5.6% on non-transfused controls. CONCLUSIONS: In contrast to earlier studies, persistent TA-MC was not observed in our cohort of trauma subjects. Short-term TA-MC was detected, but at a lower frequency than previously observed, and rates were not significantly different than what was observed in non-transfused controls. The reduction in TA-MC occurrence may be attributable to changes in leukoreduction or other blood processing methods.

Distinct roles of trauma and transfusion in induction of immune modulation after injury.

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.

Transfusion practices for acute traumatic brain injury: a survey of physicians at US trauma centers.

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.

Microchimerism decades after transfusion among combat-injured US veterans from the Vietnam, Korean, and World War II conflicts.

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.