Department of Medicine, Pediatrics and Oncology, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada.
Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program, Foothills Medical Centre, Calgary, Alberta, Canada.
Thromb Haemost. 2021 Mar;121(3):332-340. doi: 10.1055/s-0040-1718373. Epub 2020 Oct 29.
Platelet transfusion is the standard treatment to control or prevent bleeding in patients with Glanzmann's thrombasthenia (GT), but platelets are often unavailable. Recombinant activated factor VII (rFVIIa) is an effective alternative to platelets in patients with GT with past/present refractoriness to platelet transfusions and antibodies to platelets. However, there is an unmet need for an alternative to platelets in patients without antibodies. This report summarizes evidence of efficacy and safety of rFVIIa in patients with GT without refractoriness or antibodies to platelets from three different sources: the Glanzmann's Thrombasthenia Registry (GTR), published literature (January 01, 1999 to December 01, 2017), and the Novo Nordisk safety surveillance database. In the GTR, 133 patients received rFVIIa for the treatment of 333 bleeding episodes and prevention of bleeding in 157 surgical procedures. Overall efficacy rates were 79 and 88%, respectively, in patients treated for bleeding episodes or for the prevention of bleeding during surgery; effectiveness was generally similar across refractoriness/antibody status categories. Median dose per infusion of rFVIIa was close to that recommended for patients with GT (90 µg/kg). Data from 14 published case reports also demonstrated that rFVIIa is effective with an acceptable safety profile in patients with GT without antibodies to platelets. Analysis of adverse events reported in GTR and in Novo Nordisk safety surveillance database did not raise any new safety concerns. These data supported the label extension of rFVIIa to include cases where platelets are not readily available, which was approved by the European Medicines Agency in December 2018.
血小板输注是控制或预防 Glanzmann 血小板无力症（GT）患者出血的标准治疗方法，但血小板往往供应不足。重组活化因子 VII（rFVIIa）是 GT 患者对血小板输注和血小板抗体既往/现在有反应性的有效替代物。然而，对于没有抗体的 GT 患者，仍然需要血小板的替代物。本报告总结了来自三个不同来源的无反应性或无血小板抗体的 GT 患者使用 rFVIIa 的疗效和安全性证据：Glanzmann's Thrombasthenia Registry（GTR）、已发表的文献（1999 年 1 月 1 日至 2017 年 12 月 1 日）和诺和诺德安全监测数据库。在 GTR 中，133 名患者因 333 次出血发作和 157 次手术出血预防而接受 rFVIIa 治疗。分别有 79%和 88%的患者在治疗出血发作或预防手术期间出血的疗效，在反应性/抗体状态类别中，有效性基本相似。rFVIIa 每次输注的中位数剂量接近 GT 患者推荐剂量（90µg/kg）。来自 14 份已发表病例报告的数据也表明，rFVIIa 在无血小板抗体的 GT 患者中具有良好的疗效和可接受的安全性。对 GTR 和诺和诺德安全监测数据库中报告的不良事件的分析未提出任何新的安全性问题。这些数据支持了 rFVIIa 标签扩展，包括血小板不易获得的情况，该扩展于 2018 年 12 月获得欧洲药品管理局批准。
