RBC TRANSFUSION IN ANEMIC NEONATES LEADS TO SYSTEMIC INFLAMMATORY RESPONSE SYNDROME

贫血新生儿红细胞输注导致全身炎症反应综合征

基本信息

  • 批准号:
    10463828
  • 负责人:
  • 金额:
    $ 2.86万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-08-06 至 2023-03-31
  • 项目状态:
    已结题

项目摘要

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.
项目总结

项目成果

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Mohan Kumar Krishnan其他文献

Mohan Kumar Krishnan的其他文献

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{{ truncateString('Mohan Kumar Krishnan', 18)}}的其他基金

Liver-Gut Axis in Neonatal Anemia and Its Role in RBC Transfusion Associated Gut Injury
新生儿贫血中的肝肠轴及其在红细胞输注相关肠道损伤中的作用
  • 批准号:
    10583807
  • 财政年份:
    2023
  • 资助金额:
    $ 2.86万
  • 项目类别:
Liver-Gut Axis in Neonatal Anemia and Its Role in RBC Transfusion Associated Gut Injury
新生儿贫血中的肝肠轴及其在红细胞输注相关肠道损伤中的作用
  • 批准号:
    10834574
  • 财政年份:
    2023
  • 资助金额:
    $ 2.86万
  • 项目类别:
RBC TRANSFUSION IN ANEMIC NEONATES LEADS TO SYSTEMIC INFLAMMATORY RESPONSE SYNDROME
贫血新生儿红细胞输注导致全身炎症反应综合征
  • 批准号:
    10284300
  • 财政年份:
    2021
  • 资助金额:
    $ 2.86万
  • 项目类别:
Effect of Platelet Transfusions on Neonatal Intestinal Injury
血小板输注对新生儿肠损伤的影响
  • 批准号:
    9757811
  • 财政年份:
    2018
  • 资助金额:
    $ 2.86万
  • 项目类别:

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