Infection and Inflammation in Pediatric Catheter Related Venous Thrombosis

儿科导管相关静脉血栓形成的感染和炎症

基本信息

批准号：
7632201
负责人：
Leslie J Raffini
金额：
$ 15.59万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-09 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7632201
关键词：
Activated Partial Thromboplastin Time measurement Acute Address Affect Anti-Inflammatory Agents Antibiotics Anticoagulants Aspirin Like Agents Basic Science Binding Blood Coagulation Factor Blood Platelets Blood specimen Burkholderia cepacia C-reactive protein Caring Catheters Child Child Care Childhood Chronic Chronic Disease Clinical Clinical Investigator Clinical Research Coagulants Coagulation Process Cohort Studies Complication Cystic Fibrosis Data Defensins Development Dialysis procedure Dose E-Selectin Education Endothelium Etiology Excision Extracellular Fluid Factor VIII Fibrinogen Fibrinolysis Frequencies Functional disorder Future Generations Growth Ibuprofen Image In Vitro Incidence Incidence Study Infection Inflammation Inflammatory Inherited Institution Intercellular adhesion molecule 1 Interleukin-6 Interleukin-8 Intravenous Laboratories Laboratory Markers Lead Low-Molecular-Weight Heparin Malabsorption Syndromes Measurement Measures Medical Mentors Modeling Morbidity - disease rate P-Selectin Pathogenesis Pathologic Pathology Pathway interactions Patients Pharmaceutical Preparations Phlebography Pilot Projects Plasma Platelet Activation Platelet Count measurement Play Population Prevalence Prevention strategy Principal Investigator Process Prospective Studies Protein C Proteins Prothrombin time assay Recombinants Recruitment Activity Recurrence Reporting Research Design Research Personnel Respiratory physiology Risk Risk Factors Role Sampling Scientist Secondary to Sputum Subgroup Supportive care Surface Techniques Testing Therapeutic Therapeutic Intervention Thromboembolism Thrombosis Thrombus Time Training Ultrasonography Vascular Cell Adhesion Molecule-1 Venous Venous Thrombosis Viral Vitamin K Whole Blood abstracting annexin A5 antimicrobial peptide base candidate marker career chemotherapy cohort cystic fibrosis patients cytokine experience high risk hydroxyurea inflammatory marker insight interest modifiable risk mortality neonate neutrophil novel nutrition pathogen premature prevent programs prophylactic prospective respiratory vascular bed von Willebrand Factor

项目摘要

DESCRIPTION (provided by applicant): The presence of a central venous catheter (CVC) is the single most important risk factor for venous thromboembolism (VTE) is children. These catheters are often necessary for the care of premature neonates and children with acute and chronic diseases, and are used for intravenous nutrition, chemotherapy, dialysis, prolonged antibiotics, or supportive therapy. The use of CVCs to provided supportive care for ill children continues to rise, as does the incidence of complicating thrombosis. CVC-related VTE (CVC-VTE) can result in significant morbidity and mortality. Therefore, it is necessary to identify patients who are "high risk", in whom prevention strategies may be developed. This proposal will examine risk factors for the development of CVC-VTE in pediatric patients with cystic fibrosis (CF), a fairly uniform population that has repeated requirements for CVCs. Based on preliminary data by the principal investigator showing that infection by a specific pathogen correlates with risk of thrombosis, we hypothesize that systemic inflammation with consequent platelet activation in patients with CF is exacerbated by specific pathogens, resulting in a prothrombotic state that leads to the development of CVC-VTE. This proposal aims to test this hypothesis in a prospective clinical study and to define the incidence of both CVC-VTE in patients with CF, to understand the pathophysiology of these iatrogenic thrombi, and to identify laboratory markers that may help predict which CF patients are at high risk for VTE. We propose a single institution cohort study utilizing venography and ultrasound at the time of CVC placement followed by repeat imaging studies at 30 days or at the time of catheter removal in patients with CF. Specific Aim 1 will determine the incidence and prevalence of VTE in patients with CF who require a CVC. Specific Aim 2 will examine whether VTE in CF patients is associated with specific respiratory pathogens, as determined by a sputum sample. Specific Aim 3 will define the mechanisms that lead to CVC-VTE in patients with CF, focusing on a novel model on the etiologic importance of defensins in this process. These studies should provide insight into the basis of such thrombosis in a pediatric population, and lead to future studies directed at prevention strategies for high-risk patients, with and without CF. Decreasing the risk of CVC-VTE should have tremendous positive impact on the care of children with chronic diseases. The applicant is interested in establishing a career as a clinician-scientist with expertise in the care of pediatric patients with thrombosis. The above proposed studies, set within an organized effort that includes formal clinical research education and additional laboratory training, and guided by experienced and dedicated mentors, should enable the applicant to begin to successfully establish such a career. (End of Abstract)

描述（由申请人提供）：中心静脉导管（CVC）的存在是儿童静脉血栓栓塞（VTE）的唯一最重要的危险因素。这些导管通常是早产儿和患有急慢性疾病的儿童的护理所必需的，用于静脉营养、化疗、透析、长期抗生素或支持治疗。使用 CVC 为患病儿童提供支持性护理的情况持续增加，并发血栓形成的发生率也在不断增加。 CVC 相关 VTE (CVC-VTE) 可导致显着的发病率和死亡率。因此，有必要识别“高危”患者，并为其制定预防策略。该提案将研究囊性纤维化 (CF) 儿科患者发生 CVC-VTE 的危险因素，这是一个相当统一的人群，对 CVC 有重复的要求。根据主要研究者的初步数据显示特定病原体的感染与血栓形成的风险相关，我们假设特定病原体会加剧 CF 患者的全身炎症以及随后的血小板活化，导致血栓形成前状态，从而导致发展CVC-VTE。该提案旨在通过一项前瞻性临床研究检验这一假设，并确定 CF 患者中 CVC-VTE 的发生率，了解这些医源性血栓的病理生理学，并确定可能有助于预测哪些 CF 患者处于危险状态的实验室标志物。 VTE 风险高。我们建议开展一项单一机构队列研究，在 CVC 放置时使用静脉造影和超声检查，然后在 30 天或 CF 患者拔除导管时重复进行影像学研究。具体目标 1 将确定需要 CVC 的 CF 患者中 VTE 的发生率和患病率。具体目标 2 将检查 CF 患者的 VTE 是否与特定呼吸道病原体相关（通过痰样本确定）。具体目标 3 将定义导致 CF 患者发生 CVC-VTE 的机制，重点关注防御素在此过程中病因学重要性的新模型。这些研究应该可以深入了解儿科人群中此类血栓形成的基础，并引导未来针对患有或不患有CF的高危患者制定预防策略的研究。降低 CVC-VTE 风险应该会对慢性病儿童的护理产生巨大的积极影响。申请人有兴趣成为一名临床医生科学家，在血栓形成儿科患者的护理方面拥有专业知识。上述拟议的研究是在有组织的努力范围内进行的，包括正式的临床研究教育和额外的实验室培训，并由经验丰富且专注的导师指导，应使申请人能够开始成功地建立这样的职业生涯。（摘要完）