儿童免疫介导性血栓性血小板减少性紫癜(iTTP)的基础治疗是治疗性血浆置换(TPE)的组合,皮质类固醇,还有利妥昔单抗.Caplacizumab是一种抗血管性血友病因子(VWF)纳米抗体分子,已被批准为成人和12岁以上儿童的iTTP的一线治疗。根据建议,在12岁以下的儿童中使用caplacizumab仍然是一个灰色地带,但没有上市许可。我们报告了第一例iTTP的儿科患者,根据ADAMTS13活性,成功使用每天5mg的卡普拉斯珠单抗剂量调整治疗。我们还回顾了所有已发表的接受卡普拉斯珠单抗治疗的12岁以下儿童的iTTP病例。这是一个7岁的女孩,患有临床血栓性微血管病,在没有腹泻和肾损伤的情况下。法国得分为2,血浆得分为7(高风险),怀疑诊断为TTP,随后通过严重低ADAMTS13活性(<5%)证实.由于存在功能性ADAMTS13抑制剂,免疫介导的TTP与先天性TTP不同。在第0天(D0)开始每日TPE和静脉内皮质类固醇。在D4上添加利妥昔单抗,并且由于每日TPE下的难治性,我们考虑了来自D12的卡普拉斯单抗的超标签给药。一个临床答案,随着血小板计数的显著增加,在48小时内观察到。在D62达到完全ADAMTS13恢复。治疗期间未观察到重大不良事件。她在3个月前出院,血小板计数仍在正常范围内。在文学中,我们确定了总共四例病例报告,描述了5例年龄<12岁的iTTP患者接受卡普拉斯单抗治疗,100%的成功率和耐受性率。这些发表的数据证明了在12岁以下的儿科iTTP中系统使用卡普拉斯单抗和利妥昔单抗作为一线治疗的有效性和安全性。因此,需要前瞻性数据来支持在该亚群中对caplacizumab进行商业授权.对ADAMTS13活性的密切监测在儿童中特别感兴趣,以限制卡普拉斯珠单抗的注射次数。
The cornerstone treatment for immune-mediated thrombotic thrombocytopenic purpura (iTTP) in children is a combination of therapeutic plasma exchange (TPE), corticosteroids, and rituximab. Caplacizumab is an anti-von Willebrand factor (VWF) NANOBODY molecule approved as a frontline therapy of iTTP for adults and children aged ≥12 years. Using caplacizumab in children aged <12 years remains a gray area based on recommendations but with no marketing authorization. We report the first case of a pediatric patient with iTTP successfully treated with a caplacizumab dose adjustment of 5 mg daily based on ADAMTS13 activity. We also
review all published cases of iTTP in children aged <12 years treated with caplacizumab. This is a 7-year-old girl with clinical thrombotic microangiopathy, in the absence of diarrhea and kidney injury. With a French score of 2 and a PLASMIC score of 7 (high risk), the diagnosis of TTP was suspected and later confirmed by severely low ADAMTS13 activity (<5%). Immune-mediated TTP was distinguished from the congenital one due to the presence of a functional ADAMTS13 inhibitor. Daily TPE and intravenous corticosteroids were started on day 0 (D0). Rituximab was added on D4, and due to refractoriness under daily TPE, we considered off-label administration of caplacizumab from D12. A clinical answer, with a significant increase in the platelet count, was observed within 48 h. A complete ADAMTS13 recovery was reached on D62. No major adverse events were observed during the treatment. She was discharged from the hospital over 3 months ago with a platelet count still within normal ranges. In the literature, we identified a total of four case reports describing five iTTP patients aged <12 years treated with caplacizumab, with a 100% success and tolerability rate. These published data attest to the efficacy and safety of the systematic use of caplacizumab and rituximab as frontline therapy in pediatric iTTP under 12 years of age. Therefore, prospective data are needed to support commercial authorization of caplacizumab in this subpopulation. Close monitoring of ADAMTS13 activity is particularly of interest among children to limit the number of caplacizumab injections.