Meijer K, Rauchensteiner S, Santagostino E, Platokouki H, Schutgens R E G, Brunn M, Tueckmantel C, Valeri F, Schinco P C
University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Haemophilia. 2015 Jan;21(1):e19-25. doi: 10.1111/hae.12530. Epub 2014 Dec 2.
In haemophilia A, continuous infusion (CI) of FVIII perioperatively provides a more constant FVIII level than conventional bolus injections, avoiding low trough levels that could increase bleeding risk. Due to the low number of surgical cases in clinical trials, especially in haemophilia, more information on the clinical practice of CI from observational studies is helpful. We aimed to evaluate the effectiveness and safety of CI with recombinant factor VIII formulated with sucrose (rFVIII-FS) in a typical surgery practice setting. This was a non-interventional study in 12 centres. Patients with severe haemophilia A who received rFVIII-FS by CI during and after surgery were included in this study if they had more than 150 exposure days (EDs) to any FVIII product and had no history of inhibitors before CI. Patients were observed during the entire course of CI, with monitoring up to 3 months thereafter. Twenty-five patients with 28 surgeries were included in the analysis. Median age was 51.7 (range 10-75). Most (75%; 21/25) patients underwent orthopaedic surgeries. The median dose of rFVIII-FS consumed during CI was 376 IU kg(-1) (range 157.9-3605.6 IU kg(-1)) with a greater median dose for orthopaedic surgeries (424.0 IU kg(-1)) compared to non-orthopaedic surgeries (278.5 IU kg(-1)). 95% of all FVIII measurements (214/224) were on target. Efficacy and tolerability were rated as good/excellent in 89.3% (25/28) of surgeries. No inhibitors were observed during or after surgery. This study demonstrates the effectiveness of CI with rFVIII-FS during surgery in patients with severe haemophilia A in a clinical practice setting.
在甲型血友病中，围手术期持续输注（CI）凝血因子VIII（FVIII）比传统大剂量注射能提供更稳定的FVIII水平，避免了可能增加出血风险的低谷水平。由于临床试验中的手术病例数量较少，尤其是在血友病患者中，来自观察性研究的关于CI临床实践的更多信息很有帮助。我们旨在评估在典型手术实践环境中使用蔗糖配制的重组FVIII（rFVIII-FS）进行CI的有效性和安全性。这是一项在12个中心开展的非干预性研究。如果患有严重甲型血友病的患者对任何FVIII产品有超过150个暴露日（EDs）且在CI前无抑制剂病史，则在手术期间及术后接受rFVIII-FS CI的患者纳入本研究。在CI的整个过程中观察患者，并在其后长达3个月进行监测。分析纳入了25例患者的28台手术。中位年龄为51.7岁（范围10 - 75岁）。大多数（75%；21/25）患者接受了骨科手术。CI期间消耗的rFVIII-FS中位剂量为376 IU kg⁻¹（范围157.9 - 3605.6 IU kg⁻¹），与非骨科手术（278.5 IU kg⁻¹）相比，骨科手术的中位剂量更高（424.0 IU kg⁻¹）。所有FVIII测量值的95%（214/224）处于目标范围内。89.3%（25/28）的手术中疗效和耐受性被评为良好/优秀。手术期间及术后未观察到抑制剂。本研究证明了在临床实践环境中，rFVIII-FS CI对严重甲型血友病患者手术期间的有效性。
