Henrard S, Hermans C
Institute of Health and Society (IRSS), Université catholique de Louvain, Brussels, Belgium.
Haemostasis and Thrombosis Unit, Division of Haematology, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Haemophilia. 2016 May;22(3):361-7. doi: 10.1111/hae.12848. Epub 2015 Nov 11.
Treatment of haemophilia A (HA) requires infusions of factor VIII (FVIII) concentrates. The number of FVIII units infused to obtain a specific circulating FVIII level is calculated with the formula: [body weight (BW) (kg) × desired FVIII increase (%)]/2, with the assumption that each unit of FVIII infused per kg of BW increases the circulating FVIII level by 2%.
The aim of this study was to evaluate the impact of several morphometric parameters (BW, body mass index (BMI)-for-age, height), age and type of FVIII concentrate on FVIII recovery in children with HA.
A total of 66 children aged between 10 and 18 with severe HA selected from six pharmacokinetic (PK) clinical trials using two recombinant FVIII concentrates were included in the analysis. Regression tree (RT) was used to identify predictors of FVIII recovery.
The median age was 14.5 years with a median FVIII recovery of 2.09 for all children. The median FVIII recovery was not significantly different between age groups. Two groups were created by RT: children with a BMI-for-age percentile <P95 (Median FVIII recovery: 1.94) and obese children with a BMI-for-age percentile ≥P95 (Median FVIII recovery: 2.65). The FVIII recovery was significantly different between these two groups (P < 0.001).
These results are consistent with previous studies conducted in adults with HA and confirm that the long-held and current practice of applying an arbitrary and universal recovery of two to the calculations of FVIII dosage should be abolished in both children and adults.
治疗甲型血友病(HA)需要输注凝血因子VIII(FVIII)浓缩物。输注特定数量的FVIII单位以达到特定的循环FVIII水平可通过以下公式计算:[体重(BW)(kg)×所需FVIII增加量(%)]/2,前提是每千克体重输注的FVIII单位可使循环FVIII水平提高2%。
本研究旨在评估多个形态学参数(体重、年龄别体重指数(BMI)、身高)、年龄以及FVIII浓缩物类型对HA患儿FVIII恢复情况的影响。
从六项使用两种重组FVIII浓缩物的药代动力学(PK)临床试验中选取了66名年龄在10至18岁之间的重度HA患儿纳入分析。采用回归树(RT)来确定FVIII恢复情况的预测因素。
所有患儿的中位年龄为14.5岁,FVIII恢复情况的中位数为2.09。各年龄组之间的FVIII恢复情况中位数无显著差异。通过RT将患儿分为两组:年龄别BMI百分位数<P95的患儿(FVIII恢复情况中位数:1.94)和年龄别BMI百分位数≥P95的肥胖患儿(FVIII恢复情况中位数:2.65)。这两组之间的FVIII恢复情况存在显著差异(P<0.001)。
这些结果与先前针对成年HA患者开展的研究一致,并证实应摒弃长期以来在儿童和成人中计算FVIII剂量时随意且通用地采用2的恢复系数这一做法。