Does Biocompatibility Contribute to Transfusion-Related Adverse Effects?

生物相容性是否会导致输血相关的不良反应？

• 批准号: 10080105
• 负责人: Nikki Gillum Posnack
• 金额: $ 67.74万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-15 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080105
• 关键词: Address; Adoption; Adverse effects; Arrhythmia; Atherosclerosis; Autonomic Dysfunction; Biocompatible Materials; Blood; Blood Transfusion; Cardiac; Cardiopulmonary Bypass; Cardiovascular system; Cartoons; Cells; Chemical Exposure; Chemicals; Childhood; Clinical; Communities; Coupled; Critical Illness; Decision Making; Development; Devices; Endocrine Disruptors; Endocrine disruption; Exposure to; Extracorporeal Membrane Oxygenation; Foundations; Frequencies; Future; Health; Heart; Human; Hypertension; Impairment; Incentives; Incidence; Infant; Inflammatory; Inherited; Length of Stay; Medical; Medical Device; Modeling; Monitor; Myocardial Infarction; Neurologic; Outcome; Patients; Preparation; Procedures; Property; Publishing; Reaction; Risk; Role; Safety; Sickle Cell Anemia; Techniques; Thalassemia; Toxic effect; Transfusion; United States; Xenobiotics; adverse outcome; base; biomaterial compatibility; clinical effect; clinical investigation; epidemiology study; heart rate variability; improved; in vivo; insight; mortality; neonate; neurodevelopment; patient population; patient safety; pediatric patients; phthalates; premature; research study; surface coating; transfusion medicine; virtual

Project Summary Nearly 15 million transfusions are performed in the United States each year, with approximately 425,000 units transfused to pediatric patients alone. Despite the frequency – transfusion procedures are not without risk. Blood transfusion complications may be attributed to heavy exposure to plastic devices, which are fabricated with chemicals that exert endocrine disrupting properties. The proposal's main hypothesis is that plastic devices are not universally biocompatible – and that local and systemic reactions to chemical contaminants contribute to transfusion-related complications. The proposal's objective is to assess whether medical device biocompatibility and chemical exposures are underlying contributors to cardiovascular and autonomic dysfunction. The proposal also aims to identify safer biomaterials, chemicals and/or surface coatings for transfusion devices and blood banking. In this proposal, we will build upon our preliminary studies to address three specific aims: 1) To define the extent to which biomaterial leaching and chemical exposure alters cardiovascular and autonomic function, using in vivo and whole heart models. 2) To determine if biocompatibility and incidental chemical exposures are correlated with cardiovascular and autonomic abnormalities in transfused pediatric patients. 3) To compare and contrast alternative biomaterials, chemicals and fabrication techniques in order to identify safer replacements for transfusion-related devices. The proposed application will quantify the role of biocompatibility and chemical leaching on cardiovascular and autonomic function – two targets that are highly susceptible to xenobiotic toxicity. If adverse outcomes are observed in the proposed study, it will pinpoint additional variables to monitor in future clinical investigations and epidemiological studies. Finally, this proposal aims to provide the foundation for objective decision making regarding the use of chemical additives with endocrine disrupting properties in medical device manufacturing by scientific, medical and regulatory communities. Results of the proposed studies can incentivize and accelerate the development and clinical adoption of alternative biomaterials, additives and/or fabrication techniques to improve transfusion patient safety.

项目摘要 美国每年进行近1500万例输血，约42.5万例 仅为儿科病人输血。尽管输血频率很高，但输血程序并非没有风险。血样 输血并发症可能归因于大量接触塑料设备，这些塑料设备是用 具有扰乱内分泌功能的化学物质。该提案的主要假设是塑料设备是 不是普遍的生物相容--局部和系统对化学污染物的反应有助于 与输血相关的并发症。该提案的目的是评估医疗器械的生物兼容性 化学物质暴露是心血管和自主神经功能障碍的潜在贡献者。这项建议 还旨在确定用于输血设备和血液的更安全的生物材料、化学品和/或表面涂层 银行业。在这项建议中，我们将以我们的初步研究为基础，解决三个具体目标：1)界定 生物材料浸出和化学物质暴露改变心血管和自主神经功能的程度， 采用活体模型和全心模型。2)确定生物兼容性和附带的化学暴露是否 与输血儿童患者的心血管和自主神经异常相关。3)比较和 对比替代生物材料、化学品和制造技术，以确定更安全的替代品 与输血相关的设备。拟议中的应用将量化生物兼容性和化学物质的作用 对心血管和自主神经功能的淋洗--这两个目标非常容易受到异物毒性的影响。 如果在拟议的研究中观察到不利的结果，它将确定未来需要监测的其他变量 临床调查和流行病学研究。最后，这项提案旨在为 关于在医疗中使用具有内分泌干扰特性的化学添加剂的客观决策 科学、医疗和监管机构制造设备。建议的研究结果可以 鼓励和加速开发和临床采用替代生物材料、添加剂和/或 提高输血患者安全性的制造技术。