Prevention of the Complications of Thalassemia

描述（由申请人提供）：重型地中海贫血患者需要定期输注红细胞，以避免珠蛋白产生不足或缺失。由于这些终身输血计划，受影响的患者有一个强烈的和持续的暴露于血液传播的病原体，并可能是一个哨兵人口的识别新的传染性病原体的血液供应。定期输血程序也会导致其他输血相关并发症，包括红细胞同种异体免疫和铁超载。后者是治疗的特别破坏性并发症，需要定期螯合治疗以防止广泛的器官损伤和心力衰竭或心律失常的早期死亡。此前，CDC发起的预防铁过载并发症的研究开发了一项多中心研究，研究地中海贫血的输血相关并发症和其他并发症。目前的研究提供了一个机会，继续定期收集相关的临床，人口和遗传数据，以解决的主要目标的特点和预防地中海贫血的并发症。费城儿童医院地中海贫血项目将利用各种战略和工具，继续在监测项目中招募患者，建立消费者输入方法，评估和满足未得到服务或服务不足人群的需求，提供多学科综合护理，识别新获得的输血传播感染和其他疾病相关和治疗相关并发症的患者，并传播研究结果。此外，我们的地中海贫血项目已经确定了两个新的研究领域：（1）使用纵向队列来描述重型地中海贫血患者的当前死亡率以及与治疗中心内外治疗相关的死亡率差异;（2）确定脾切除术后事件的当前风险，特别是败血症和血栓形成。 总的来说，这些研究将更好地确定地中海贫血的最佳治疗方法，也将有助于改善其他需要定期输注红细胞的疾病的治疗。通过详细描述地中海贫血的并发症，拟议的研究不仅将改善这种遗传性血液疾病的管理，而且还将影响所有需要短期和长期红细胞输注计划的患者的治疗。

DESCRIPTION (provided by applicant): Patients with thalassemia major require regular red cell transfusions to circumvent their deficient or absent production of globin. As a consequence of these lifelong transfusion programs, affected patients have an intense and sustained exposure to blood-borne pathogens and may be a sentinel population for the recognition of new infectious agents in the blood supply. Regular transfusion programs also lead to other transfusion-related complications including red cell alloimmunization and iron overload. The latter is a particularly devastating complication of therapy and requires regular chelation therapy to prevent widespread organ damage and early death from cardiac failure or arrhythmias. Previously, the CDC- sponsored Prevention of Complications of Iron Overload developed a multi-center study of transfusion- related and other complications of thalassemia. The present study offers an opportunity to continue the regular collection of relevant clinical, demographic and genetic data to address the major goals of characterizing and preventing the complications of thalassemia. Using a variety of strategies and tools, The Thalassemia Program of the Children's Hospital of Philadelphia will continue to enroll patients in the surveillance projects, establish methods for consumer input and assess and meet the needs of unserved or underserved populations, provide multi-disciplinary, comprehensive care, identify patients with newly acquired transfusion-transmitted infections and other disease-related and treatment-related complications, and disseminate the study findings. In addition, our Thalassemia Program has identified two areas of new investigation: (1) the use of the longitudinal cohort to characterize the current mortality of patients with thalassemia major and differences in mortality related to treatment in or outside of a treatment center and (2) defining the current risk of postsplenectomy events, in particular sepsis and thrombosis. Overall, these studies will better define the optimal therapy of thalassemia and will also contribute to improvements in the treatment of other disorders requiring regular red cell transfusions. Project Narrative By characterizing in detail the complications of thalassemia, the proposed studies will not only improve the management of this inherited blood disorder but will also influence the treatment of all patients requiring short-term and long-term red cell transfusion programs.