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，以避免其珠蛋白产生不足或缺失。作为这些终生输血计划的结果，受影响的患者有强烈和持续的血液传播病原体暴露，并可能成为识别血液供应中新的感染源的哨兵人群。定期输血还会导致其他与输血相关的并发症，包括红细胞免疫和铁超载。后者是一种特别具有破坏性的治疗并发症，需要定期进行螯合治疗，以防止广泛的器官损害和因心力衰竭或心律失常而导致的早期死亡。此前，CDC赞助的预防铁超载并发症开展了一项关于输血相关并发症和地中海贫血其他并发症的多中心研究。本研究提供了继续定期收集相关临床、人口学和遗传学数据的机会，以实现确定和预防地中海贫血并发症的主要目标。费城儿童医院地中海贫血计划将使用各种策略和工具，继续将患者纳入监测项目，建立消费者投入的方法，评估和满足未得到服务或服务不足的人群的需求，提供多学科、全面的护理，识别新感染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，我们的地中海贫血计划确定了两个新的研究领域：(1)使用纵向队列来表征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；以及(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。总体而言，这些研究将更好地确定地中海贫血的最佳治疗方法，并将有助于改进其他需要定期输注红细胞的疾病的治疗。项目简介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治疗，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.