RBC TRANSFUSION IN ANEMIC NEONATES LEADS TO SYSTEMIC INFLAMMATORY RESPONSE SYNDROME

项目总结 输注红细胞(RBCT)对早产儿和危重患者是必要的和挽救生命的 患病的婴儿，由于生理和医源性因素而经历严重贫血。最近， 我们已经证明，严重贫血与肠道通透性增加有关， 从血液中内毒素的鉴定中可以看出。此外，还有 越来越多的人认识到血库储存前必要步骤的危险 输血。储存的红细胞的输注会被肝巨噬细胞迅速清除，从而产生 非转铁蛋白结合铁(NTBI)在血浆中循环，通过 组织中的铁沉积。在关键发育阶段经历严重贫血的风险 周期必须与输血风险相平衡，输血风险可能导致全身炎症。 反应综合征(SIRS)和潜在的多器官功能障碍综合征(MODS)。这个 贫血与输血直接或间接相关的潜在机制(S) SIRS的发展仍不清楚。对红细胞之间关联性的批判性评估 输血和全身炎症反应综合征是改善临床实践和制定治疗策略所必需的 预防和/或改善贫血-RBCT相关性SIRS。调查与RBCT相关的 SIRS，研究人员使用了现有的小鼠模型，在该模型中，10天大的小鼠幼崽 在出生后(P)2-10天内进行定时静脉采血以导致严重贫血 (血球压积18%-22%)，此时他们接受静脉输注红细胞，然后 观察时间长达24小时。基于初步数据，研究人员提出了一种新的假设 贫血新生儿特别容易发生全身炎症反应综合征，这是因为 由于肠道屏障功能的丧失，缺氧肠道中的细菌产物，促进 肝脏单核细胞对预先形成的细胞因子的反应；RBCT可以加强这一效应。那里 有两个特定的目标：(1)确定新生儿肝脏(NL)来源的病理生理作用 单核细胞在贫血和输血时全身炎症反应综合征发生发展中的作用(二)确定 是否阻断肝单核细胞上的tem1活性和/或恢复贫血相关 肠道通透性可预防/改善输血相关贫血 先生们。拟议目标的实现将解释这些机制和潜力 危重病患者RBCT输注相关全身炎症反应综合征的预防和/或治疗策略 新生儿。

Project summary Transfusions of Red Blood Cells (RBCT) are necessary and life-saving in premature and critically ill infants, who experience severe anemia due to both physiologic and iatrogenic factors. Recently, we have shown that severe anemia was associated with increased intestinal permeability, demonstrated by the identification of endotoxin in the bloodstream. Additionally, there is increasing recognition of the dangers of the necessary step of blood bank storage prior to transfusion. Transfusions of stored RBCs are rapidly cleared by liver macrophages, producing non-transferrin bound iron (NTBI) to circulate in plasma, acutely inducing inflammation through iron deposition in tissues. The risks of experiencing severe anemia during critical developmental periods must be balanced with the risks of transfusions, which can lead to Systemic Inflammatory Response Syndrome (SIRS) and potentially Multi Organ Dysfunction Syndrome (MODS). The underlying mechanism(s) by which anemia and transfusion directly or indirectly correlate with the development of SIRS remain unclear. Critical evaluation of the association between RBC transfusion and SIRS is necessary to improve clinical practice and develop therapeutic strategies to prevent and/or ameliorate anemia-RBCT associated SIRS. To investigate RBCT associated SIRS, the investigators used an existing murine model in which 10-day-old mouse pups were subjected to timed phlebotomy between postnatal days (P) 2-10 to induce severe anemia (hematocrits 18%-22%), at which point they received an intravenous RBC transfusion, then observed for up to 24h. Based on preliminary data, the investigators propose a novel hypothesis that anemic neonates are uniquely predisposed to SIRS because of direct transmigration of bacterial products from the hypoxic intestine due to loss of intestinal barrier function, facilitating the hepatic monocyte response with preformed cytokines; RBCT can potentiate this effect. There are two specific aims: (1) Determine the pathophysiological role of neonatal liver (NL)-derived monocytes in the development of SIRS during anemia and RBC transfusion. (2) Determine whether blocking trem1 activity on liver monocyte and/or restoration of anemia-associated intestinal permeability can prevent/ameliorate anemia-transfusion associated SIRS. Accomplishment of the proposed aims will explain the mechanisms and potential strategies to prevent and/or treat anemia-RBCT transfusion associated SIRS in critically-ill neonates.