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: 8058698
• 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/8058698
• 关键词: Activated Partial Thromboplastin Time measurement; Acute Disease; 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; Protein S; 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; citrate carrier; 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（由申请方提供）：中心静脉导管（CVC）的存在是儿童静脉血栓栓塞（VTE）的单一最重要风险因素。这些导管通常是早产儿和患有急性和慢性疾病的儿童的护理所必需的，并用于静脉营养，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继续增加，并发血栓形成的发生率也在增加。CVC相关性VTE（CVC-VTE）可导致显著的发病率和死亡率。因此，有必要确定谁是“高风险”的患者，在其中可以制定预防策略。该提案将研究囊性纤维化（CF）儿科患者发生CVC-VTE的风险因素，CF是一个相当均匀的人群，重复需要CVC。根据主要研究者的初步数据显示特定病原体感染与血栓形成风险相关，我们假设CF患者的全身炎症伴血小板活化因特定病原体而加重，导致血栓前状态，进而导致CVC-VTE的发生。本提案旨在通过前瞻性临床研究验证这一假设，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患者具有VTE高风险的实验室标志物。我们提出了一个单一的机构队列研究，利用静脉造影和超声在CVC放置时，随后在30天或在导管移除CF患者的时间重复成像研究。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，如通过痰液样本确定的。具体目标3将定义导致CF患者CVC-VTE的机制，重点是防御素在此过程中的病因学重要性的新模型。这些研究应该提供深入了解这种血栓形成的基础上，在儿科人群，并导致未来的研究针对预防策略的高风险患者，有和没有CF。降低CVC-VTE的风险应该对慢性病儿童的护理产生巨大的积极影响。申请人有兴趣建立一个职业生涯作为一个临床医生，科学家与专业知识的护理儿科患者血栓形成。上述拟定研究在有组织的努力中进行，包括正式的临床研究教育和额外的实验室培训，并由经验丰富的专业导师指导，应使申请人开始成功建立这样的职业生涯。(End摘要）