Effect of Platelet Transfusions on Neonatal Intestinal Injury

摘要 坏死性小肠结肠炎（NEC）是早产儿的特发性炎症性肠坏死， 是妊娠32周前出生的新生儿死亡的主要原因。临床研究表明，90%以上的 确诊NEC的患者发生血小板减少症，但由于 目前为止，调查关注度有限。因为患有NEC的早产儿也有严重的风险， 出血并发症，如脑室内出血，NEC危重婴儿的血小板减少症 通常通过血小板输注进行治疗（以纠正血小板计数，而不是实际出血）。 有一些证据表明血小板输注与NEC的不良结局有关，但血小板输注 继续在这些患者中广泛使用，因为问题仍然存在， 接受血小板输注治疗的婴儿反映了输注血小板的副作用， 这些婴儿疾病严重程度较高的混杂效应。了解病理生理作用 NEC患者的血小板计数对合理输血至关重要。为了调查这些问题，调查人员 已经开发了NEC相关血小板减少症的小鼠模型，并产生了关于 血小板的病理生理作用和血小板减少的机制在NEC。三个具体目标 提出：（1）阐明NEC时血小板减少症发生的机制， 并建立NEC期间血小板消耗的主要部位;（2）确定血小板减少对 NEC期间肠损伤;（3）确定血小板输注对NEC期间肠损伤的影响。 NEC。在第三个目标中，研究人员还将比较新鲜血小板与储存血小板的炎症反应， 方面的影响.所提出的目标的实现将产生新的见解血小板的影响， 输血对新生儿肠损伤的影响关于血小板免疫调节作用的重要信息 还将获得新生儿输血。这些研究还将为以下方面提供重要的参考点： 早产儿和肠损伤期间输血实践的临床评价。

ABSTRACT Necrotizing enterocolitis (NEC) is an idiopathic, inflammatory bowel necrosis of premature infants, and a leading cause of mortality in neonates born prior to 32 weeks' gestation. Clinical studies show that >90% of patients with confirmed NEC develop thrombocytopenia, but the underlying mechanisms remain unclear due to limited investigative attention so far. Because premature infants who develop NEC are also at risk of serious bleeding complications such as intraventricular hemorrhage, thrombocytopenia in a critically-ill infant with NEC is usually treated prophylactically with platelet transfusions (to correct the platelet count, not actual bleeding). There is some evidence to link platelet transfusions with adverse outcomes in NEC, but platelet transfusions continue to be used widely in these patients because the question remains whether the inferior outcomes of infants treated with platelet transfusions reflect the adverse effects of the transfused platelets or merely the confounding effect of the higher severity of illness of these infants. Understanding the pathophysiological role of platelets in NEC is critical for rational transfusion practices. To investigate these questions, the investigators have developed murine models of NEC-related thrombocytopenia and generated preliminary data on the pathophysiological role of platelets and the mechanisms of thrombocytopenia during NEC. Three specific aims are proposed: (1) Elucidate the mechanisms underlying the development of thrombocytopenia during NEC, and establish major sites of platelet consumption during NEC; (2) Determine the effect of thrombocytopenia on intestinal injury during NEC; and (3) Determine the effect of platelet transfusions on intestinal injury during NEC. In the third aim, the investigators will also compare fresh vs. stored platelets for their inflammatory effects. Accomplishment of the proposed aims will generate novel insights into the effects of platelet transfusions on neonatal intestinal injury. Important information on the immunomodulatory effects of platelet transfusions in neonates will also be obtained. These studies will also provide important reference points for clinical evaluation of transfusion practices in premature infants and during intestinal injury.