Immune Thrombocytopenia and Low-Level Mercury Exposure

描述(由申请人提供)： 西格尔博士正在寻求这个以患者为导向的指导奖，以研究美国免疫性血小板减少性紫癜(ITP)的表皮病学，进行一项横断面研究，检查ITP患者中汞与相关自身抗体的关系，并发起建立ITP患者队列进行纵向研究。这些活动将有助于她成为一名独立的临床研究员。 关于ITP在美国的流行病学信息很少。总的来说，自身免疫性疾病是卫生保健系统中一个未得到充分认识的负担，而ITP可能是一个重要因素，因为受影响的患者需要定期住院治疗、手术干预，通常还需要终生药物治疗。西格尔博士将使用两个大型国家数据库--全国住院患者样本和全国医院非卧床医疗护理调查--来调查ITP患者的患病率、性别和性别分布、合并疾病以及资源消耗情况。 发生在成人的慢性ITP的病因仍不确定，但可能与易感基因患者的环境因素有关。为此，西格尔博士将收集横断面数据，旨在调查汞在慢性ITP患者中的作用。她将测量血液和脚趾甲中汞的浓度和与低水平汞暴露有关的自身抗体，以及抗血小板糖蛋白抗体。预计汞相关自身抗体的患者将有很高的血小板特异性抗体患病率。未来的研究将旨在调查这些对汞的自身免疫效应敏感的患者的免疫基因类型，这可能会为这类患者提供新的治疗方法。 最后，西格尔博士将试行建立ITP患者队列进行纵向研究。这将促进与其他机构的研究人员的合作，这些研究人员可能有兴趣将ITP患者纳入队列研究。 西格尔博士在抗凝血和自体血液使用的流行病学等血液相关主题的临床研究方面拥有强大的临床和研究培训以及早期的记录。由一位熟练的流行病学家、一位具有丰富重金属经验的环境科学家以及一位在血小板紊乱方面有专长的血液学家/病理学家的指导，将为西格尔博士的成功完成提供必要的支持。

DESCRIPTION (provided by applicant): Dr. Segal is seeking this Mentored Patient-Oriented Award to study the epiderniology of immune thrombocytopenic purpura (ITP) in the United States, to conduct a cross-sectional study examining mercury's association with relevant autoantibodies in patients with ITP, and to initiate the establishment of a cohort of patients with ITP for longitudinal study. These activities will contribute to her becoming an independent clinical researcher. There is scant information on the epidemiology of ITP in the United States. Autoimmune diseases, collectively, are an under-recognized burden on the health care system and ITP may be a substantial contributor, as affected patients require periodic inpatient care, surgical interventions, and often life-long medical therapy. Dr. Segal will use two large national databases, the Nationwide Inpatient Sample and the Nationwide Hospital Ambulatory Medical Care Survey, to investigate the prevalence of disease, sex and gender distribution, comorbid illnesses, and consumption of resources by patients with ITP. The etiology of chronic ITP, as occurs in adults, remains uncertain, but may involve an environmental trigger in patients with a susceptible genotype. To this end, Dr. Segal will collect cross-sectional data aimed at investigating the role of mercury in patients with chronic ITP. She will measure blood and toenail mercury concentrations and autoantibodies which have been associated with low-level mercury exposure, as well as anti-platelet glycoprotein antibodies. It is expected that patients with mercury-associated autoantibodies will have a high prevalence of platelet-specific antibodies. Future research will be aimed at investigating the immunogenotypes of these patients who demonstrate susceptibility to the autoimmune effects of mercury, which may suggest new therapies for this subset of affected patients. Finally, Dr. Segal will pilot the establishment of a cohort of patients with ITP for longitudinal study. This will facilitate collaboration with researchers at other institutions who may be interested in enrolling patients with ITP in cohort studies. Dr. Segal has strong clinical and research training and an early track record in clinical research in blood-related topics including anticoagulation and the epidemiology of autologous blood use. The mentoring by a skilled epidemiologist, an environmental scientist with extensive heavy metal experience, and a hematologist/pathologist with expertise in platelet disorders, will provide Dr. Segal with the necessary support for successful completion