Regional Reference Centre for Coagulation Disorders, Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.
Br J Haematol. 2010 Sep;150(5):515-28. doi: 10.1111/j.1365-2141.2010.08263.x. Epub 2010 Jun 22.
Immune tolerance induction (ITI) is the only strategy proven to eradicate persistent inhibitors in severe haemophilia A patients. Thirty years experience has shown high success rates (60-80%) with heterogeneous dose regimens and has led to the identification of clinical features that define the patients' prognostic profile. Children with recently diagnosed inhibitors are the best candidates for ITI and adequate management may further contribute to improve the short- and long-term ITI outcome. In these patients inhibitor eradication represents a cost-effective option because it enables the restoration of FVIII prophylaxis and consequently prevents arthropathy development. Adults with long-standing inhibitors often show bad predictors of ITI outcome, however, ITI may be considered as a suitable and cost-effective approach in cases with frequent bleeds that are not satisfactorily controlled by by-passing treatment and/or when orthopaedic surgery is needed. Optimal ITI regimens should be established in these different settings and randomized trials are addressing these issues. This article reviews the available literature evidence and clinical implications with current recommendations on ITI management, and highlights the issues still unsolved.
免疫耐受诱导（ITI）是唯一被证明可消除重型血友病 A 患者持续性抑制剂的策略。30 年的经验表明，采用不同剂量方案的成功率很高（60-80%），并确定了可定义患者预后特征的临床特征。近期诊断出抑制剂的儿童是 ITI 的最佳候选者，适当的管理可能有助于改善短期和长期 ITI 结果。在这些患者中，抑制剂的消除是一种具有成本效益的选择，因为它可以恢复 FVIII 预防治疗，从而防止关节病的发展。长期存在抑制剂的成年人通常具有 ITI 结果的不良预测因素，但是，对于频繁出血且旁路治疗和/或矫形外科手术不能充分控制的患者，ITI 可被视为一种合适且具有成本效益的方法。应在这些不同情况下制定最佳的 ITI 方案，并且正在进行随机试验来解决这些问题。本文回顾了现有文献证据和临床意义，提出了当前关于 ITI 管理的建议，并强调了仍未解决的问题。
