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

• 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
• 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

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）：中央静脉导管（CVC）的存在是静脉血栓栓塞（VTE）最重要的危险因素。这些导管通常对于护理过早的新生儿和患有急性和慢性疾病的儿童是必需的，并且用于静脉营养，化学疗法，透析，长时间的抗生素或支持疗法。使用CVC为患病儿童提供支持性护理的使用，使血栓形成复杂的发生率也在继续上升。与CVC相关的VTE（CVC-VTE）可能导致显着的发病率和死亡率。因此，有必要识别“高风险”的患者，其中可能会制定预防策略。该提案将研究囊性纤维化（CF）患者中CVC-VTE发展的危险因素，这是一种相当统一的人群，对CVC的重复要求。基于主要研究者的初步数据，表明特定病原体的感染与血栓形成的风险相关，我们假设，特定病原体的CF患者的全身性炎症会导致血小板激活，从而导致了蛋白酶的状态，从而导致CVC-VTE的发展。该提案旨在在一项前瞻性临床研究中检验这一假设，并确定CF患者两种CVC-VTE的发生率，了解这些医源性血栓的病理生理学，并鉴定实验室标记物，以帮助预测哪些CF患者对VTE的高风险有很高的风险。我们建议在CVC放置时使用静脉造影和超声检查，然后在30天或在CF患者中去除导管时进行反复成像研究。具体目标1将确定需要CVC患者VTE的发病率和患病率。特定的目标2将检查CF患者的VTE是否与痰样品确定的特定呼吸病原体有关。具体目标3将定义导致CF患者CVC-VTE的机制，重点介绍了在此过程中防御素的病因学重要性的新型模型。这些研究应提供对小儿人群中这种血栓形成的基础的见解，并导致针对有或没有CF的高危患者进行预防策略的未来研究。降低CVC-VTE的风险应该对慢性疾病儿童的护理产生巨大的积极影响。申请人有兴趣建立从事临床医生的职业，该职业在患有血栓形成的儿科患者方面具有专业知识。以上提议的研究是在有组织的工作中设定的，其中包括正式的临床研究教育和其他实验室培训，并在经验丰富和专门的导师的指导下，应使申请人能够开始成功建立这样的职业。 （抽象的结尾）