Impact of patient’s body build on replacement therapy in haemophilia A: a review of evidence in both children and adults

Henrard, Séverine [UCL] Hermans, Cédric [UCL]

Introduction: The number of factor VIII (FVIII) units infused in order to obtain a specific circulating FVIII level in haemophilia A (HA) 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 the present study was to evaluate the impact of several morphometric parameters (body mass index (BMI) for adults or BMI-for-age for children), age and type of coagulation factor concentrate on the FVIII recovery in a large group of children and adults. Methods: A total of 201 adults (>18 years) and 72 children (6-17 years) with HA carefully selected from 8 pharmacokinetic clinical trials using Advate®, Kogenate FS® or ReFacto AF/Xyntha® were included in the analysis. The FVIII recovery was calculated using the maximum FVIII concentration measured at 15 and 30 minutes after infusion. BMI and BMI-for-age cut-off values to determine overweight, normal weight, overweight and obesity were taken from the literature and defined as body mass categories. Regression tree (RT) was used to identify predictors of FVIII recovery. RT-based models are non-linear and non-parametric alternatives to linear models for regression problems. Results: The median FVIII recovery of 2.15 for all patients. The median FVIII recovery was significantly different body mass categories (p<0.001) with a median FVIII recovery of 1.72, 1.97, 2.18 and 2.64 for underweight (n=11), normal (n=149), overweight (n=60) and obese patients (n=53), respectively. The median age was similar in these 4 groups (p=0.070). In multivariate analysis, 2 groups were created by RT: underweight, normal and overweight patients (Group 1; Median [P25; P75] FVIII recovery: 2.04 [0.51; 2.35]) and obese patients (Group 2; Median [P25; P75] FVIII recovery: 2.64 [2.36; 2.84]). The FVIII recovery was significantly different between these two groups (P<0.001). Discussion/ Conclusion: Our findings support that dose calculation of FVIII to reach a specific FVIII target level should be adapted in both obese children and adults since only a small fraction of FVIII distributes outside the vascular system. These results confirm that the long-held and current practice of applying an arbitrary and universal recovery of 2 to the calculations of FVIII dosage should be abolished.