RUSH Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, IL, USA.
Haemophilia. 2011 Jul;17(4):579-89. doi: 10.1111/j.1365-2516.2010.02460.x. Epub 2011 Feb 7.
Patients with congenital haemophilia with inhibitors are at risk of peri-operative bleeding complications, since replacement of the missing coagulation factor is ineffective, presenting a therapeutic challenge in elective or emergency surgery. Therefore, the management of peri-operative bleeding requires the use of bypassing agents, such as recombinant activated FVII (rFVIIa, NovoSeven(®) ). This article presents an updated evaluation of the safety and effectiveness of rFVIIa in the treatment of peri-operative bleeding in this patient population. Surgical and other medical procedures managed with rFVIIa from two randomized clinical trials, the Hemophilia Research Society/Hemophilia and Thrombosis Research Society (HRS/HTRS) registry databases and the medical literature were analysed. There were 395 rFVIIa-treated procedures (261 surgical, 89 dental and 45 other medical procedures) reported for 263 congenital haemophilia patients with inhibitors. In trials, initial rFVIIa dosing was 35-90 mcg kg(-1) bolus injection or 50 mcg kg(-1) h(-1) continuous infusion. Dosing in the registries and literature was more variable. Recombinant FVIIa effectiveness was comparable across data sources, with an overall rate of 84% (333/395). The incidence of thrombotic events was very low (0.4% of patients and 0.025% of procedures). Prior to the US approval of rFVIIa in 1999, surgical procedures in congenital haemophilia patients with inhibitors were often considered too risky. Recombinant FVIIa has consistently demonstrated effectiveness in treatment of bleeding in these patients during such procedures. Thrombotic events were rare. This analysis confirms the value of corroborating clinical trial results with post-marketing surveillance registries to assess small patient populations with clinically challenging management decisions.
患有抑制物的先天性血友病患者在围手术期有出血并发症的风险，因为替代缺失的凝血因子无效，这在择期或急诊手术中带来了治疗挑战。因此，围手术期出血的管理需要使用旁路制剂，如重组激活的 FVII（rFVIIa，诺和诺德公司的 NovoSeven(®)）。本文对 rFVIIa 在治疗该患者人群围手术期出血方面的安全性和有效性进行了更新评价。对两项随机临床试验、血友病研究学会/血友病和血栓形成研究学会（HRS/HTRS）登记数据库和医学文献中使用 rFVIIa 管理的手术和其他医疗程序进行了分析。报告了 263 例有抑制物的先天性血友病患者的 395 例 rFVIIa 治疗程序（261 例手术、89 例牙科和 45 例其他医疗程序）。在试验中，初始 rFVIIa 剂量为 35-90 mcg/kg 推注或 50 mcg/kg/h 持续输注。登记处和文献中的剂量更为多变。来自不同数据来源的 rFVIIa 有效性相当，总体有效率为 84%（333/395）。血栓事件的发生率非常低（0.4%的患者和 0.025%的程序）。在 1999 年 rFVIIa 获得美国批准之前，有抑制物的先天性血友病患者的手术通常被认为风险太大。rFVIIa 在这些患者的手术中治疗出血一直被证明是有效的。血栓事件很少见。该分析证实了在评估具有临床挑战性管理决策的小患者人群时，将临床试验结果与上市后监测登记处进行核对的价值。
