Body weight and fat mass index as strong predictors of in vivo factor VIII recovery in adults with hemophilia A

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

Background. The treatment of hemophilia A requires preventive or curative intravenous injections of clotting factor VIII (FVIII) concentrates. The number of units of FVIII to be infused depends of the following Oxford’s formula: [body weight (BW) (kg) × desired FVIII increase (%)] / 2, which is based on the assumption that each unit of FVIII infused per kg of BW increases the FVIII level by 2 % in the patient’s blood, since the 70’s. Objectives. The aim of this study is to validate the value of the in vivo FVIII recovery and study its relation to morphometric variables (BW, fat mass index, body mass index and difference between BW and ideal BW). Patients/Methods. FVIII recovery was measured in 46 not actively bleeding hemophilia A patients after administration of a dose of recombinant FVIII concentrate (Advate®, Kogenate® or Refacto®). Kruskall-Wallis tests were used to compare continuous variables between groups and regression trees were used to identify morphometric predictors of FVIII recovery. Results. The median FVIII recovery was 2.08 in the whole sample. It was 2.63 for patients with a BW ≥ 81.0 kg and 1.87 for patients with a BW < 81.0 kg (p<0.001). The FVIII recovery was significantly higher in patients with a fat mass index (FMI) ≥ 20% compared to patients with a FMI < 15% (median FVIII recovery: 2.35 vs 1.74; p=0.007). Using multivariate analysis, regression trees divided the patients into three homogeneous groups according to FVIII recovery: patients with BW < 80.5 kg and FMI < 22.3%, patients with BW < 80.5 kg and FMI ≥ 22.3% and patients with BW ≥ 80.5 kg. Median FVIII recovery in these 3 groups was 1.80, 2.16 and 2.63 respectively (p<0.001). Conclusions. FVIII dosing should take into account the BW and the FMI and should be individualized in underweight or overweight patients according to the individual recovery. A FVIII recovery value of 2 can only be used for normal BW patients with a FMI in the range of 15 to 20%. A comparison of the average recovery reported with different FVIII concentrates in clinical study should consider the morphometric characteristics of studied patients.