PLATELETS AND BLOOD FLOW IN SICKLE CELL DISEASE

镰状细胞病中的血小板和血流

基本信息

批准号：
2735275
负责人：
Theodore Wun
金额：
$ 10.33万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-07-13 至 2000-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2735275
关键词：
cell adhesion conjunctiva erythrocytes fibronectins flow cytometry fluorescent dye /probe human subject intravital microscopy microcirculation monoclonal antibody platelet activation platelet aggregation receptor sickle cell anemia thrombospondins

项目摘要

Vascular occlusive events account for much of the morbidity and mortality in patients with sickle cell disease. The pathogenesis of these vaso- occlusive events remains ill-defined and the subject of much speculation. The focus of this research proposal will be the role of platelet activation and platelet-erythrocyte aggregates in vaso-occlusive events. We hypothesize the following: 1) There is baseline platelet activation in patients with sickle cell disease which increases during vaso-occlusive crisis, 2) increased platelet activation is negatively correlated with blood flow in the microvasculature, 3) circulating platelet-erythrocyte aggregates (PEA) are present in patients with sickle cell disease and increase during vaso-occlusive events and, 4) platelet-erythrocyte aggregation is mediated by thrombospondin and fibronectin. Using fluorescent-labeled antibodies to activation-dependent and -independent platelet antigens, red cell antigens, and flow cytometry, longitudinal studies of patients with sickle cell disease will be done to determine the degree of platelet activation and platelet-erythrocyte aggregate formation and their relation to clinical events. Platelet activation and PEA will be correlated with blood flow as measured by computer-assisted intravital microscopy of the bulbar conjunctiva. The role of fibronectin and thrombospondin in PEA formation will be studied by the incubation of platelets and red cells from patients and normals, in the presence and absence of antibodies to these adhesive proteins or their receptors. These data will fill gaps in the knowledge of the degree arid persistence of platelet activation, microcirculatory blood flow abnormalities, and platelet-red cell interactions in sickle call patients.

血管闭塞事件是发病率和死亡率的主要原因镰状细胞病患者。这些血管的发病机制闭塞事件仍然不明确，并且是许多猜测的主题。该研究计划的重点是血小板的作用血管闭塞事件中的激活和血小板红细胞聚集。我们假设如下： 1) 存在基线血小板活化患有镰状细胞病的患者，其在血管闭塞期间会增加危机，2）血小板活化增加与微血管中的血流，3) 循环血小板红细胞镰状细胞病患者体内存在聚集物（PEA）血管闭塞事件期间增加，4) 血小板-红细胞聚集由血小板反应蛋白和纤连蛋白介导。使用激活依赖性和非依赖性的荧光标记抗体血小板抗原、红细胞抗原和流式细胞术，纵向将对镰状细胞病患者进行研究以确定血小板活化和血小板-红细胞聚集体形成的程度及其与临床事件的关系。血小板活化和 PEA 将与计算机辅助活体测量的血流量相关球结膜显微镜检查。纤连蛋白的作用和将通过孵育来研究 PEA 形成中的血小板反应蛋白来自患者和正常人的血小板和红细胞，在存在和缺乏针对这些粘附蛋白或其受体的抗体。这些数据将填补关于程度和持久性的知识空白血小板活化、微循环血流异常、镰状细胞病患者中血小板与红细胞的相互作用。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Improved survival with plasma exchange in patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.

血浆置换可提高血栓性血小板减少性紫癜-溶血性尿毒症综合征患者的生存率。

DOI：
发表时间：
1999-12
期刊：
影响因子：
0
作者：
Lara Jr, P N;Coe, T L;Zhou, H;Fernando, L;Holland, P V;Wun, T
通讯作者：
Wun, T

Platelet activation and platelet-erythrocyte aggregates in patients with sickle cell anemia.

镰状细胞性贫血患者的血小板活化和血小板红细胞聚集。

DOI：
发表时间：
1997-05
期刊：
影响因子：
0
作者：
Wun, T;Paglieroni, T;Tablin, F;Welborn, J;Nelson, K;Cheung, A
通讯作者：
Cheung, A

Correlation of abnormal intracranial vessel velocity, measured by transcranial Doppler ultrasonography, with abnormal conjunctival vessel velocity, measured by computer-assisted intravital microscopy, in sickle cell disease.

在镰状细胞病中，通过经颅多普勒超声检查测量的异常颅内血管速度与通过计算机辅助活体显微镜测量的异常结膜血管速度的相关性。

DOI：
10.1182/blood.v97.11.3401
发表时间：
2001-06-01
期刊：
Blood
影响因子：
20.3
作者：
A. Cheung;P. Harmatz;Theodore Wun;Peter C. Y. Chen;E. Larkin;R. Adams;E. Vichinsky
通讯作者：
E. Vichinsky

Thrombopoietin is synergistic with other hematopoietic growth factors and physiologic platelet agonists for platelet activation in vitro.

血小板生成素与其他造血生长因子和生理性血小板激动剂具有协同作用，可在体外激活血小板。