Van Creveldkliniek, Department of Hematology, and Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.
Haemophilia. 2011 May;17(3):433-8. doi: 10.1111/j.1365-2516.2010.02450.x. Epub 2011 Feb 7.
Replacement therapy or prophylaxis, has become the standard of care for the treatment of severe haemophilia A. To describe bleeding patterns in children, adolescents and adults on prophylaxis and their observed relationships to times of infusion (during the week and during the day) as well as season of the year. Data from Advate pre-licensure prospective clinical trials from 145 patients with factor VIII (FVIII) <1%, were used. All patients underwent a 48-h pharmacokinetic study. The 10-65 year group had ≥ 75 exposure days on fixed prophylaxis (25-40 IU kg(-1) 3-4x per week). Prophylaxis was not fixed but similar for 1-6 year olds. Bleeding patterns were analysed. Overall, 700 bleeds were observed in 110/145 patients. All were treated with prophylaxis, mean dose 108 IU kg(-1) week(-1) in on average 2.9 infusions (1-6 years), 86 IU kg (-1) week(-1) in 2.7 infusions (10-17 years), and 75 IU kg (-1) week(-1) in 2.6 infusions (18-65 years), respectively. On prophylaxis, median total bleeds per year were low at 3.1 for patients aged 1-6 years, 3.3 for those aged 10-17 years and 2.1 for patients aged 18-65 years. Patients aged 1-6 years had predominantly soft tissue bleeds (79%). Incidence of joint bleeding was not associated with season, but was significantly lower in patients who infused FVIII in the mornings: median 0 per year (IQR 0.0-0.4) compared to those who infused later [median 1.8 per year (IQR 0.0-5.2)]. Older patients predominantly experienced joint bleeds (50% and 62%, respectively). More joint bleeds occurred during the summer [43 and 46% respectively, (P < 0.01)]. Bleeding patterns in patients on prophylaxis varied according to age. In addition, the 10-65 year olds showed increased bleeding during the summer. After confirmation in prospective studies, this information may be used to improve tailoring of prophylactic treatment.
替代疗法或预防治疗已成为治疗严重甲型血友病的标准。描述预防治疗中儿童、青少年和成年人的出血模式，并观察其与输注时间（一周内和一天内）以及一年中季节的关系。使用了来自 Advate 上市前前瞻性临床试验的 145 名 FVIII ＜1%患者的数据。所有患者均进行了 48 小时药代动力学研究。10-65 岁组在固定预防治疗中有≥75 天的暴露（25-40IU kg(-1) 每周 3-4 次）。1-6 岁儿童的预防治疗不固定，但相似。分析出血模式。总体而言，145 名患者中有 110 名观察到 700 例出血。所有患者均接受预防治疗，平均剂量为每周 108IU kg(-1)，平均输注 2.9 次（1-6 岁），86IU kg(-1)，每周 2.7 次（10-17 岁），75IU kg(-1)，每周 2.6 次（18-65 岁）。在预防治疗中，1-6 岁患者每年总出血中位数较低，为 3.1 次，10-17 岁患者为 3.3 次，18-65 岁患者为 2.1 次。1-6 岁患者主要发生软组织出血（79%）。关节出血的发生率与季节无关，但在早上输注 FVIII 的患者中明显较低：每年中位数 0 次（IQR 0.0-0.4），而稍后输注的患者每年中位数为 1.8 次（IQR 0.0-5.2）。年龄较大的患者主要发生关节出血（分别为 50%和 62%）。夏季关节出血发生率较高（分别为 43%和 46%，P < 0.01）。预防治疗患者的出血模式随年龄而变化。此外，10-65 岁患者在夏季出血增加。在前瞻性研究中得到证实后，这些信息可能用于改善预防性治疗的个体化。
