• Fifty percent of TA-GVHD cases occur in patients who would not be predicted to be at risk for TA-GVHD by current guidelines for blood irradiation.• Donor lymphocytes whose HLA antigens are all shared by the recipient dominate in TA-GVHD cases, particularly in immune-competent recipients.Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare complication of blood transfusion. The clinicolaboratory features of TA-GVHD and the relative contributions of recipient and component factors remain poorly understood. We conducted a systematic review of TA-GVHD reports. The HLA relationship between donor and recipient was classified as D 5 0 when no donor antigens were foreign to the recipient vs D ‡ 1 when ‡1 donor antigen disparity occurred. We identified 348 unique cases. Criteria for component irradiation were met in 48.9% of cases (34.5% immune-compromised, 14.4% related-donor), although nonirradiated components were transfused in the vast majority of these (97.6%). Components were typically whole blood and red cells. When reported, component storage duration was £10 days in 94%, and 23 (6.6%) were leukoreduced (10 bedside, 2 prestorage, and 11 unknown). Among 84 cases with HLA data available, the category of D 5 0 was present in 60 patients (71%) at either HLA class I or II loci and was more common among recipients without traditional indications for component irradiation. These data challenge the historic emphasis on host immune defects in the pathogenesis of TA-GVHD. The dominant mechanism of TA-GVHD in both immunocompetent and compromised hosts is exposure to viable donor lymphocytes not recognized as foreign by, but able to respond against, the recipient. (Blood. 2015;126(3):406-414)

Background: Transfusion of packed red blood cells (PRBcs) saves lives in the neonatal critical care setting and is one of the most common interventions in the preterm infant. The number and volume of PRBc transfusions are associated with several major neonatal morbidities, although a direct causal link between transfusion and major neonatal morbidity is still to be proven. Transfusion-related immunomodulation (TRIM) may underlie these adverse outcomes, yet it has received little attention in the high-risk preterm infant. Methods: One transfusion event was studied in infants ≤28 wk gestation between 2 and 6 wk postnatal age (n = 28). Plasma inflammatory cytokines and markers of endothelial activation were measured in the infants before and 2-4 h after transfusion, as well as in the donor pack. results: Median (range) age at transfusion was 18 (14-39) days with the pretransfusion hemoglobin level at 9.8 (7.4-10.2) g/dl. Interleukin (IL)-1β (P = 0.01), IL-8 (P = <0.001), tumor necrosis factor-α (P = 0.008), and monocyte chemoattractant protein (P = 0.01) were increased after transfusion. a similar elevation in markers of endothelial activation was seen after transfusion with increased plasma macrophage inhibitory factor (P = 0.005) and soluble intracellular adhesion molecule-1 (P = <0.001). conclusion: Production of inflammatory cytokines and immunoactivation of the endothelium observed after the transfusion of PRBcs in the preterm infant may be a manifestation of TRIM. The implications of this emerging phenomenon within the preterm neonatal population warrant further investigation. t ransfusion of blood products is not benign. In adults, transfusion is an independent predictor of death and is associated with an increased incidence of multiorgan system failure, length of hospital stay, infection risk, and modulation of the immune system (1,2). Although the mechanisms underlying these associations are yet to be comprehensively characterized, a two-hit model of posttransfusion injury has been proposed (3). In the clinical setting of an underlying inflammatory state priming the recipient's immune system, transfusion of packed red blood cells (PRBCs) may trigger immune cell activation and related immunomodulation, resulting in frank inflammation (4). This transfusion-related immunomodulation (TRIM), encompassing not only adverse proinflammatory and immunosuppressive responses but also the whole spectrum of posttransfusion effects on organs and tissues, has been proposed to underlie much of the increased transfusionassociated morbidity and mortality seen in adults (4).In the neonatal population, there is an increasing awareness of the excess morbidity and mortality associated with PRBC transfusions (5,6). PRBC transfusions have been implicated in the development of problems not encountered in the adult population, including chronic lung disease (7), retinopathy of prematurity (8), and necrotizing enterocolitis (9,10), with the incidence and severity of these conditions correlating with the number and volume of PRBC tran...

Blood product use remains at a very high frequency in preterm neonates born at less than 30 weeks' gestation. Evolutionary practice changes and relative high tolerance for anemia may be associated with a reduction in RBC usage in recent years in neonates born at at least 26 weeks' gestation. This contrasts with the ongoing higher usage of blood products observed at extremely low gestational ages.

There was a high risk of death or impairment in this cohort of infants. Survival was rare for AGA infants weighing ≤500 g at birth. Our study provides an evidence base to assist counselling and decision-making.

Statistically significant differences in a range of harmful outcomes between neonates exposed to restrictive and liberal RBC transfusion practice were not found. However, the risks of bias identified in many studies and the lack of consistent reporting and definitions of events limits our conclusions.

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Circulating NTBI is transiently elevated following blood transfusion in preterm newborns. This increase was related to the age of blood transfused and correlated with increases in oxidative stress but not pro-inflammatory cytokines. While further studies are necessary to determine whether these transient effects influence clinical outcome, the current data do not support a significant role in the very preterm neonate for NTBI in TRIM.

Background: Necrotizing enterocolitis (NEC) is a serious complication of prematurity. Currently, there is limited evidence to guide investigation and treatment strategies. Objectives: To evaluate the parameters used to diagnose or exclude NEC, and to identify differences between neonatologists and pediatric surgeons. Methods: A scenario-based survey was sent to neonatologists and pediatric surgeons. Results: 173 physicians from 26 countries completed the survey (55% neonatologists and 45% pediatric surgeons). Bloody stools, abdominal tenderness, low platelet counts, and increased lactate levels increased the likelihood of NEC for 82, 72, 56, and 45% of respondents, respectively. Intestinal pneumatosis, portal venous gas, and pneumoperitoneum on X-ray increased the likelihood of NEC for 99, 98, and 92% of respondents, respectively. Clinical examination and laboratory tests were insufficient to exclude NEC, but normal intestinal movements and normal gut wall thickness on ultrasonography decreased the likelihood of NEC for 38 and 33% of respondents, respectively. Neonatologists more frequently relied on increased gastric residuals and abdominal distension to diagnose NEC (p = 0.04 and p = 0.03, respectively), whereas pediatric surgeons more frequently reported that absence of bloody stools helped to exclude NEC (p = 0.04). In a deteriorating patient with suspected NEC, 39% of respondents would broaden the antibiotic spectrum, and 42% would recommend a laparotomy. Conclusion: Our results indicate a wide variation in the management of NEC, with significant differences between neonatologists and pediatric surgeons. A better appreciation of the relative significance and weighting that should be applied to the clinical features and investigations should reduce the variation in interpretation that appears to exist.