Hemostasis Consortium

描述(由申请人提供)： 该提案描述了位于达拉斯的俄克拉荷马大学健康科学中心和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。描述了指导实习生和初级教员的计划。提出了解决止血中尚未解决的重要问题的方案。方案1：血栓性血小板减少性紫癜(TTP)患者的初始治疗：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TTP已被证明是有效的，但一些患者有多重加重，需要长期治疗。糖皮质激素的疗效未经证实，可能是因为之前报道的患者有不同的病因。最近观察到，针对von Willebrand因子裂解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依据。据推测，大剂量糖皮质激素(甲基强的松龙，1000毫克，连续3天，然后强的松，1毫克/公斤/天)将改善临床结果。糖皮质激素治疗的良好结果将提示进一步研究免疫抑制方案。方案2：儿童特发性血小板减少性紫癜(ITP)的初始治疗：抗D(标准治疗)对照观察。美国血液学会(ASH)ITP实践指南中最具争议的话题是儿童ITP的初始管理。ASH小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/肿瘤学学会最近的调查一致。然而，英国儿科血液学小组的指导方针建议，仅进行观察就可以作为适当的初始治疗。随机临床试验已经证明，随着治疗的进行，血小板计数恢复得更快，但还没有研究描述药物治疗对出血的临床结果和生活质量的影响。据推测，新的严重出血发作将等同于接受抗D-D治疗的儿童或仅通过观察来管理，并且儿童及其父母的生活质量将在仅通过观察来管理时更好。相同的临床结果将支持避免具有潜在危害和全球可获得性有限的昂贵治疗的做法。

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.