Hemostasis Consortium

止血联盟

• 批准号: 6571425
• 负责人: JAMES N GEORGE
• 金额: $ 30万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6571425
• 关键词: adult human (21+); biomedical facility; blood disorder chemotherapy; blood transfusion; children; clinical research; clinical trials; combination therapy; cooperative study; glucocorticoids; hemorrhage; hemostasis; human subject; human therapy evaluation; immunosuppressive; isoantibody; longitudinal human study; methylprednisolone; patient care management; patient oriented research; pediatrics; prednisone; quality of life; thrombocytopenic purpura

DESCRIPTION (provided by applicant): This proposal describes the capacity of the University of Oklahoma Health Sciences Center and the University of Texas Southwestern Medical Center at Dallas to support a Core Clinical Center for the Transfusion Medicine/Hemostasis Clinical Research Network. Key personnel have expertise in hemostasis, transfusion medicine, protocol design, Clinical trial execution, and data analysis. Programs for mentoring trainees and junior faculty are described. Protocols are proposed that address important unresolved issues in hemostasis. Protocol 1: Initial management of patients with thrombotic thrombocytopenic purpura (TTP): plasma exchange treatment (standard therapy) compared to plasma exchange treatment plus high-dose glucocorticoid. Plasma exchange treatment has proven efficacy for TTP, however some patients have multiple exacerbations and require prolonged treatment. Glucocorticoids are of unproven efficacy, possibly because previously reported patients have heterogeneous etiologies. Recent observations that autoantibodies to von Willebrand factor-cleaving protease are the etiology for TTP in many patients provide a rationale for immunosuppressive treatment. It is hypothesized that high-dose glucocorticoid (methylprednisolone, 1,000 mg for 3 days followed by prednisone, 1 mg/kg/day) will improve clinical outcomes. Superior outcomes with glucocorticoid treatment would suggest further investigation of immunosuppressive regimens. Protocol 2: Initial management of children with idiopathic thrombocytopenic purpura (ITP): anti-D (standard therapy) compared to observation. The most controversial topic addressed by the American Society of Hematology (ASH) ITP Practice Guideline was the initial management of childhood ITP. The majority opinion of the ASH panel favored drug treatment over observation, consistent with recent surveys of the American Society of Pediatric Hematology/Oncology. However guidelines by the British Paedriatric Haematology Group recommend observation alone as appropriate initial management. Randomized clinical trials have demonstrated that the platelet count recovers more rapidly with treatment, but no studies have described the effect of drug treatment on clinical outcomes of bleeding and quality-of life. It is postulated that new episodes of severe bleeding will be equivalent between children treated with anti-D or managed by observation alone, and that the quality-of-life of children and their parents will be better when managed with observation alone. Equivalent clinical outcomes would support the practice of avoiding expensive treatment with potential harms and limited world-wide availability.

描述（由申请人提供）： 本提案描述了俄克拉荷马州大学健康科学中心和位于达拉斯的德克萨斯大学西南医学中心支持输血医学/止血临床研究网络核心临床中心的能力。 关键人员具有止血、输血医学、方案设计、临床试验执行和数据分析方面的专业知识。 指导学员和初级教师的方案进行了说明。 提出了解决止血中重要的未解决问题的方案。 方案1：血栓性血小板减少性紫癜（TTP）患者的初始管理：血浆置换治疗（标准治疗）与血浆置换治疗加大剂量糖皮质激素的比较。 血浆置换治疗已被证明对TTP有效，但有些患者有多次加重，需要延长治疗时间。糖皮质激素的疗效未经证实，可能是因为以前报告的患者有异质性病因。 最近的观察表明，血管性血友病因子裂解蛋白酶的自身抗体是许多患者TTP的病因，这为免疫抑制治疗提供了理论基础。 假设高剂量糖皮质激素（甲基强的松龙，1,000 mg，持续3天，随后是泼尼松，1 mg/kg/天）将改善临床结局。 糖皮质激素治疗的上级结果提示进一步研究免疫抑制方案。 方案2：特发性血小板减少性紫癜（ITP）儿童的初始管理：抗D（标准治疗）与观察比较。 美国血液学会（ASH）ITP实践指南中最具争议的主题是儿童ITP的初始管理。 ASH专家组的大多数意见倾向于药物治疗而不是观察，这与美国儿科血液学/肿瘤学协会最近的调查一致。 然而，英国儿科血液学小组的指南建议仅观察作为适当的初始管理。 随机临床试验表明，治疗后血小板计数恢复更快，但没有研究描述药物治疗对出血和生活质量临床结局的影响。据推测，接受抗D治疗或仅通过观察管理的儿童之间新发严重出血事件将是等效的，并且当仅通过观察管理时，儿童及其父母的生活质量将更好。 等同的临床结局将支持避免具有潜在危害和全球可用性有限的昂贵治疗的实践。