Highly purified VWF/FVIII concentrates in the treatment and prophylaxis of von Willebrand disease: the PRO.WILL study
Highly purified VWF/FVIII concentrates in the treatment and prophylaxis of von Willebrand disease: the PRO.WILL study
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DOI：
10.1111/j.1365-2516.2007.01573.x
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发表时间：
2007-12-01
期刊：
影响因子：
3.9
通讯作者：
Federici, A. B.
中科院分区：
文献类型：
--
作者：
Federici, A. B.
血管性血友病（VWD）有两种治疗方法：(i)去氨加压素（DDAVP）诱导内皮室释放内源性血管性血友病因子（VWF）；（ii）输入外源性VWF/FVIII血浆衍生浓缩物中所含的VWF。只有少数高纯度的VWF/FVIII浓缩物在药代动力学（PK）试验以及VWD的回顾性或前瞻性疗效研究中得到了广泛的评估。2002年，alpha研究小组发表了PK和临床疗效研究的结果。疗效结果显示，75%的出血事件通过1 - 2次输注得到控制，71%的患者接受手术或侵入性手术的预防性治疗，临床反应良好。在另一项回顾性研究中，意大利的22名VWD患者接受了Fanhdi，一种类似于alphaate的VWF浓缩物。在92%的出血发作和93%的外科手术中观察到极好的临床反应。最近，Fanhdi的疗效和安全性在一个更大的意大利患者队列（n = 103）中进行了回顾性评估，其中97%（出血）和99%（手术）的临床反应为优秀/良好。在瑞典收集了35例严重VWD患者的VWD二级预防方面的最大经验。二级预防也在一组意大利VWD患者中实施。7例3型（n = 1）、2A型（n = 4）、2M型（n = 1）和I型（n = 1）患者因胃肠道出血而开始预防，4例3型VWD患者因关节出血而开始预防。预防措施完全防止了8名患者出血，并大大减少了其余3名患者因输血而住院的时间。现在将在意大利组织的一项大型前瞻性研究（PRO.WILL）中调查这些预防方案与按需治疗的成本效益。
Two therapeutic approaches are available to manage patients with von Willebrand disease (VWD): (i) the release of endogenous von Willebrand factor (VWF) from endothelial compartments induced by desmopressin (DDAVP); (ii) the transfusion of exogenous VWF contained in VWF/FVIII plasma-derived concentrates. Only a few high-purity VWF/FVIII concentrates have been extensively evaluated in pharmacokinetic (PK) trials as well as in retrospective or prospective efficacy studies in VWD. The Alphanate Study Group published results of PK and clinical efficacy studies in 2002. Efficacy results showed that 75% of bleeding episodes were controlled with one or two infusions, and 71% of patients who received prophylactic treatment for surgeries or invasive procedures had good clinical responses. In another retrospective study, 22 VWD patients in Italy received Fanhdi, a VWF concentrate similar to Alphanate. Excellent-good clinical responses were seen in 92% of bleeding episodes and in 93% of surgical procedures. More recently, the efficacy and safety of Fanhdi have been evaluated retrospectively in a larger cohort of Italian patients (n = 103) with 97% (bleedings) and 99% (surgeries) of excellent/good clinical responses. The largest experience on secondary prophylaxis in VWD has been collected in Sweden in 35 patients with severe forms of VWD. Secondary prophylaxis was also implemented in a cohort of Italian patients with VWD. Prophylaxis was started because of GI bleeds in seven patients with types 3 (n = 1), 2A (n = 4), 2M (n 1) and type I (n = 1) and for Joint bleeds in four patients with type 3 VWD (n = 4). Prophylaxis prevented bleeding completely in eight patients and largely reduced hospitalization for blood transfusions in the remaining three. The cost-effectiveness of these prophylaxis regimens versus on demand therapy will be now investigated in one large prospective study (PRO.WILL) organized in Italy.