Hemostasis Consortium

止血联盟

• 批准号: 6798921
• 负责人: JAMES N GEORGE
• 金额: $ 3.21万
• 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 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6798921
• 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）： 该建议描述了俄克拉荷马大学健康科学中心和达拉斯西南医学中心的能力，以支持输血医学/止血临床研究网络核心临床中心。 关键人员在止血，输血医学，方案设计，临床试验执行和数据分析方面具有专业知识。 描述了指导学员和初级教师的计划。 提出了解决止血中重要的未解决问题的方案。 方案1：与血浆交换治疗（标准治疗）与血浆交换治疗以及高剂量糖皮质激素相比，血栓性血小板减少性紫癜（TTP）的初始管理：血浆交换治疗（标准治疗）。 血浆交换治疗已证明对TTP有效，但是有些患者患有多次恶化，需要延长治疗。糖皮质激素具有未经证实的功效，可能是因为先前报道的患者具有异质性病因。 最近的观察结果是，von Willebrand因子切割蛋白酶的自身抗体是许多患者的病因，这为免疫抑制治疗提供了理由。 假设高剂量糖皮质激素（甲基泼尼松龙，1,000毫克3天，然后是泼尼松，1 mg/kg/day）将改善临床结果。 糖皮质激素治疗的卓越结果将表明对免疫抑制方案的进一步研究。 协议2：与观察相比，特发性血小板减少紫癜（ITP）的初始治疗：抗D（标准疗法）。 美国血液学学会（ASH）ITP实践指南最有争议的话题是儿童ITP的初步管理。 ASH面板的多数意见支持药物治疗而不是观察，这与美国儿科血液学/肿瘤学会的最近调查一致。 但是，英国小分子血液学小组的指南建议单独观察作为适当的初始管理。 随机临床试验表明，血小板计数通过治疗更快地恢复，但是没有研究描述了药物治疗对出血和生活质量的临床结果的影响。据推测，在接受抗D治疗或仅通过观察治疗的儿童之间，严重出血的新事件将等效，而单独观察时，儿童及其父母的生活质量会更好。 同等的临床结果将支持避免对潜在危害和全球范围有限的昂贵治疗的做法。