EVALUATION OF PLATELET PRODUCTION IN NEONATES WITH SEVERE AND PROLONGED THROMBO

严重和长期血栓新生儿血小板生成的评估

• 批准号: 7374634
• 负责人: Martha C. Sola-Visner
• 金额: $ 6万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7374634
• 关键词: EVALUATION; PLATELET; PRODUCTION; NEONATES; SEVERE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Thrombocytopenia is one of the most common hematologic problems among patients in Neonatal Intensive Care Units (NICU), affecting 20-35% of NICU patients. In thrombocytopenic adults, the administration of recombinant thrombopoietin (rTpo) is being investigated as an alternative to platelet transfusions. Results from our previous in vitro and in vivo studies have suggested that rTpo administration could be an effective therapy for thrombocytopenic neonates. Since rTpo does not increase the platelet count until 4 to 6 days after starting therapy, however, the only appropriate candidates would be neonates whose thrombocytopenia is severe and prolonged. Unfortunately, the application of new therapies to thrombocytopenic neonates has been significantly hampered by our lack of understanding of even the basic kinetic mechanisms responsible for their thrombocytopenias (platelet destruction vs. decreased platelet production). With the development of rTpo, there is now a pressing need to clarify these mechanisms. With this in mind, we designed this study to; (1) identify the kinetic mechanisms responsible for severe and prolonged thrombocytopenia in NICU patients, and (2) establish the correlation between peripheral blood and bone marrow indicators of thrombopoiesis in thrombocytopenic neonates. To accomplish this, we will use techniques specifically developed for the study of megakaryocyte mass and ploidy in the bone marrow of neonates, and will correlate these with newly developed indirect measures of thrombopoiesis (i.e. reticulated platelet counts, serum Tpo concentrations, and circulating megakaryocyte progenitors).

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。血小板减少症是新生儿重症监护病房（NICU）患者中最常见的血液学问题之一，影响了20-35％的NICU患者。在血小板减少型成年人中，正在研究重组血小板素（RTPO）作为血小板输血的替代品。我们以前的体外和体内研究的结果表明，RTPO给药可能是对血小板减少新生儿的有效疗法。但是，由于RTPO直到开始治疗后4至6天才增加血小板计数，因此唯一合适的候选者是新生儿，其血小板减少症很严重且延长。不幸的是，由于我们对导致其血小板细胞减少症的基本动力学机制的理解，新疗法在血小板减少新生儿中的应用受到了极大的阻碍（血小板破坏与血小板产生减少）。随着RTPO的发展，现在有必要澄清这些机制。考虑到这一点，我们将这项研究设计为； （1）确定NICU患者中负责严重和长时间血小板减少症的动力学机制，以及（2）建立血小板减少症新生儿血栓形成的外周血和骨髓指标之间的相关性。为了实现这一目标，我们将使用专门开发的技术来研究新生儿骨髓中的巨核细胞质量和倍性，并将这些技术与新开发的血栓形成间接度量相关联（即网状血小板计数，血清TPO，血清TPO浓度，以及循环的梅加卡毛毛毛毛质细胞增生）。