Haemophilia Centre of Perugia, Internal and Vascular Medicine, Via G. Dottori 1, Perugia, Italy.
Blood Transfus. 2011 Jan;9(1):60-9. doi: 10.2450/2010.0011-10. Epub 2010 Apr 30.
The in vivo recovery of recombinant factor IX (rFIX) is reported to be lower than that of plasma-derived products, with potential clinical implications for dosing. In clinical practice, a conversion (augmentation) factor is suggested to calculate the necessary doses of rFIX. The aim of this study was to assess the range of values for the conversion factor in usual clinical practice in Italy.
The study was questionnaire-based and proposed to all Italian Haemophilia centres treating patients with haemophilia B. Age, weight, dosage used in the last effective infusion, treatment regimen (prophylaxis versus on-demand), human immunodeficiency virus (HIV) and hepatitis C virus (HCV) status, and years of previous therapy with rFIX were recorded for patients with severe haemophilia B treated with rFIX. Mean, standard deviation, median and range were calculated for demographic and treatment data for the overall population and for subgroups. The conversion factor for the theoretical dosage of 40 IU/Kg was calculated.
Among 207 patients with severe haemophilia B being followed in 24 centres, 138 (66.7%) were being treated with rFIX. The sample of 207 patients represents 83.1% of the population of Italian patients with severe haemophilia B. The age range of the studied patients was 0-72 years (mean, 24 years) and the weight range was 3-108 kg (mean, 60 kg). Nineteen patients (14.4%) were positive for HIV and 51 (42.9%) were positive for HCV. The mean dosage of rFIX was 44 IU/Kg, with no significant difference between those receiving the product as prophylaxis or on-demand. A reduction in dosage was observed with increasing age (0.23 IU/kg/year). The mean value for the conversion factor was 1.10 ± 0.36 (median 1.00, range 0.51-2.08), when estimated for the whole population. No effect of HIV and HCV status was found on the dose prescribed. No evident correlation was found with the underlying genetic mutation.
We found that dosing of rFIX in clinical practice is very close to that of plasma-derived FIX concentrates. As a consequence, dosing in the non-surgical setting should be started using the same criteria as those for plasma-derived FIX and treatment effectiveness verified on a clinical basis rather than relying on in vivo recovery assessments.
与血浆源性产品相比，重组因子 IX（rFIX）的体内回收率较低，这可能对剂量有潜在的临床影响。在临床实践中，建议使用转换（增效）因子来计算 rFIX 的必要剂量。本研究旨在评估意大利临床实践中常用的转换因子范围。
本研究采用问卷调查的形式，向所有治疗乙型血友病患者的意大利血友病中心提出。记录了接受 rFIX 治疗的重度乙型血友病患者的年龄、体重、最后一次有效输注的剂量、治疗方案（预防治疗与按需治疗）、人类免疫缺陷病毒（HIV）和丙型肝炎病毒（HCV）状态以及之前接受 rFIX 治疗的年数。对接受 rFIX 治疗的 207 例重度乙型血友病患者的人口统计学和治疗数据进行了计算，得到了总体人群和亚组的平均值、标准差、中位数和范围。计算了理论剂量为 40 IU/Kg 的转换因子。
在 24 个中心接受治疗的 207 例重度乙型血友病患者中，有 138 例（66.7%）接受 rFIX 治疗。207 例患者的样本代表了意大利重度乙型血友病患者人群的 83.1%。研究患者的年龄范围为 0-72 岁（平均 24 岁），体重范围为 3-108 公斤（平均 60 公斤）。19 例（14.4%）患者 HIV 阳性，51 例（42.9%）HCV 阳性。rFIX 的平均剂量为 44 IU/Kg，预防治疗与按需治疗之间无显著差异。随着年龄的增长，剂量呈下降趋势（0.23 IU/kg/年）。当估计整个人群时，转换因子的平均值为 1.10 ± 0.36（中位数为 1.00，范围为 0.51-2.08）。未发现 HIV 和 HCV 状态对所开剂量有影响。与潜在的遗传突变也没有明显的相关性。
我们发现，临床实践中 rFIX 的剂量非常接近血浆源性 FIX 浓缩物。因此，非手术环境中的剂量应使用与血浆源性 FIX 相同的标准开始，而不是依赖于体内回收率评估，治疗效果应根据临床情况进行验证。
