Santagostino E, Mancuso M E, Rocino A, Mancuso G, Scaraggi F, Mannucci P M
Department of Internal Medicine and Dermatology, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation and University of Milan, Milan, Italy.
J Thromb Haemost. 2006 Feb;4(2):367-71. doi: 10.1111/j.1538-7836.2006.01772.x.
A multicenter randomized open-label crossover prospective trial was designed to compare the efficacy, safety, and cost of standard and high dosages of recombinant factor VIIa (rFVIIa) for home treatment of hemarthroses in hemophiliacs with inhibitors.
Patients were instructed to treat, within 6 h from the onset of bleeding, four consecutive hemarthroses of ankles, knees, or elbows, either with the rFVIIa standard dose of 90 microg kg(-1) (repeated as necessary every 3 h) or with a single high dose of 270 microg kg(-1). Patients who did not achieve a clinical success within 9 h continued rFVIIa treatment with repeated standard doses. Response to treatment was assessed for up to 48 h by patients/caregivers, who reported on a Visual Analogue Scale (VAS) graded from 0 to 100 the improvement in symptoms and also rated the responses as effective, partially effective or ineffective. Success was defined a treatment course rated as effective and with a VAS score > or =70 and failure a treatment course rated as ineffective and VAS score < or =30, whereas treatment courses that did not fulfill these criteria were considered partial responses.
Twenty hemophiliacs with inhibitors were originally enrolled (median age: 27 years), 18 of them treated 32 hemarthroses assigned to the standard-dosage and 36 to the high-dosage regimen, during the study period of 18 months. Forty-eight hemarthroses (71%) occurred in target joints. Success rates for standard- and high-dosage regimens were similar: 31% and 25% at 9 h, 53% and 50% at 24 h, 66% and 64% at 48 h, the end point for outcome assessment. The median number of rFVIIa infusions needed to achieve a successful course was significantly greater for the standard-dosage (n = 3) than for the high-dosage regimen (n = 1), and the median amount of rFVIIa ultimately used per successful course was identical (270 microg kg(-1)).
Our results indicate that a high-dosage regimen with rFVIIa for home treatment of hemarthroses is effective, safe, does not imply an increased consumption of rFVIIa and requires the infusion of a smaller number of rFVIIa doses. Its convenience is particularly relevant in cases with difficult venous access and in hemorrhages into target joints.
设计一项多中心随机开放标签交叉前瞻性试验，以比较标准剂量和高剂量重组凝血因子VIIa（rFVIIa）用于血友病抑制物患者关节积血家庭治疗的疗效、安全性和成本。
指导患者在出血发作后6小时内，使用90微克/千克的rFVIIa标准剂量（必要时每3小时重复一次）或270微克/千克的单次高剂量，连续治疗脚踝、膝盖或肘部的四次关节积血。在9小时内未取得临床成功的患者继续使用重复的标准剂量进行rFVIIa治疗。患者/护理人员对治疗反应进行长达48小时的评估，他们在视觉模拟量表（VAS）上对症状改善情况进行评分，评分范围为0至100，并将反应评为有效、部分有效或无效。成功定义为一个治疗疗程被评为有效且VAS评分≥70，失败定义为一个治疗疗程被评为无效且VAS评分≤30，而未达到这些标准的治疗疗程被视为部分反应。
最初纳入了20名有抑制物的血友病患者（中位年龄：27岁），在18个月的研究期间，其中18名患者对32次关节积血采用标准剂量治疗，36次采用高剂量方案治疗。48次关节积血（71%）发生在目标关节。标准剂量和高剂量方案的成功率相似：在9小时时分别为31%和25%，在24小时时分别为53%和50%，在48小时时分别为66%和64%，48小时为结局评估终点。达到成功疗程所需的rFVIIa输注中位数，标准剂量组（n = 3）显著高于高剂量方案组（n = 1），而每个成功疗程最终使用的rFVIIa中位数相同（270微克/千克）。
我们的结果表明，高剂量rFVIIa方案用于关节积血的家庭治疗是有效、安全的，并不意味着rFVIIa消耗量增加，且所需的rFVIIa输注次数较少。其便利性在静脉通路困难的病例和目标关节出血的情况下尤为重要。
