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Effect of Platelet Transfusions on Neonatal Intestinal Injury

血小板输注对新生儿肠损伤的影响

基本信息

批准号：
9389892
负责人：
Akhil Maheshwari
金额：
$ 37.38万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2018-04-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9389892
关键词：
Address Adverse effects Age Animal Model Animals Antibodies Attention Blood Platelets Bone Marrow Clinical Research Consumption Critical Illness Data Development Drops Epithelial Ethics Evaluation Evolution Exposure to Funding Opportunities Glycoproteins Hemorrhage Hour Human Immature Platelet Infant Inferior Inflammation Mediators Inflammatory Inflammatory Response Injury Intestines Kinetics Knowledge Life Link Mediating Megakaryocytes Morbidity - disease rate Mus Necrosis Necrotizing Enterocolitis Neonatal Pathogenesis Patients Platelet Count measurement Platelet Transfusion Ploidies Pregnancy Premature Infant Production Protocols documentation Research Personnel Risk Role Savings Severities Severity of illness Site Thrombocytopenia Transfusion adverse outcome animal model development base experience immunoregulation infant outcome insight intraventricular hemorrhage macrophage monocyte mortality mouse model neonate novel peripheral blood pre-clinical prophylactic pup research clinical testing

项目摘要

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.

摘要