Children's Center for Cancer and Blood Disorders, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA.
Haemophilia. 2012 Nov;18(6):990-6. doi: 10.1111/j.1365-2516.2012.02864.x. Epub 2012 May 28.
Control of bleeding in patients with congenital haemophilia with inhibitors requires use of bypassing agents such as recombinant activated factor VII (rFVIIa). Due to the difficulties in performing prospective clinical trials in this small subgroup of patients with haemophilia and the need for postmarketing surveillance, a large-scale database was developed by the Hemophilia and Thrombosis Research Society. This report comprises an analysis of the database with respect to assessing dosing and efficacy of rFVIIa by bleed type and location. Between January 2004 and November 2008, data from 129 inhibitor patients with 2041 rFVIIa-treated bleeds were analysed. The bleeds were primarily spontaneous (58%) and traumatic (30%). The most common locations were joints (57%), muscle (20%), mucosal (7%) and subcutaneous (6%). Median total rFVIIa doses per bleeding episode for spontaneous and traumatic bleeds were 540 mcg kg(-1) (4 injections/2 days) and 300 mcg kg(-1) (2.5 injections/1 day) respectively. Median total rFVIIa dose (mean dose, number of injections) was 480 mcg kg(-1) (110 mcg kg(-1) , 3) for joint; 557 mcg kg(-1) (120 mcg kg(-1) , 4) for muscle; 360 mcg kg(-1) (120 mcg kg(-1) , 3) for mucosal and 402 mcg kg(-1) (117 mcg kg(-1) , 3) for subcutaneous. Overall efficacy ranged from 89% to 93%; bleeding stopped in 89% of spontaneous and 93% of traumatic bleeds, 90% of joint bleeds, and 89% of muscle, mucosal,and subcutaneous bleeds. Although spontaneous bleeds require slightly higher doses than traumatic bleeds, most bleeds were treated with a median of 3-4 injections (110-130 mcg kg(-1) ). Effectiveness of rFVIIa was consistently high across bleeding types and locations.
患有抑制物的先天性血友病患者的出血控制需要使用旁路制剂，如重组活化因子 VII（rFVIIa）。由于在血友病这一亚组患者中进行前瞻性临床试验存在困难，并且需要进行上市后监测，因此血友病和血栓形成研究协会开发了一个大型数据库。本报告分析了该数据库，评估了按出血类型和部位评估 rFVIIa 剂量和疗效的情况。2004 年 1 月至 2008 年 11 月，对 129 名抑制物患者的 2041 例 rFVIIa 治疗出血的资料进行了分析。这些出血主要是自发性（58%）和创伤性（30%）。最常见的部位是关节（57%）、肌肉（20%）、粘膜（7%）和皮下（6%）。自发性和创伤性出血的每例出血事件 rFVIIa 的总剂量中位数分别为 540 mcg kg(-1)（4 次注射/2 天）和 300 mcg kg(-1)（2.5 次注射/1 天）。关节的 rFVIIa 总剂量中位数（平均剂量，注射次数）为 480 mcg kg(-1)（110 mcg kg(-1)，3 次），肌肉为 557 mcg kg(-1)（120 mcg kg(-1)，4 次），粘膜为 360 mcg kg(-1)（120 mcg kg(-1)，3 次），皮下为 402 mcg kg(-1)（117 mcg kg(-1)，3 次）。总体疗效为 89%至 93%；自发性出血停止率为 89%，创伤性出血停止率为 93%，关节出血停止率为 90%，肌肉、粘膜和皮下出血停止率为 89%。虽然自发性出血所需的剂量略高于创伤性出血，但大多数出血均以中位数 3-4 次注射（110-130 mcg kg(-1)）进行治疗。rFVIIa 的有效性在各种出血类型和部位均保持较高水平。
