Monitoring rFVIII prophylaxis dosing using global haemostasis assays

Secondary factor VIII (FVIII) prophylaxis converts severe haemophiliacs (FVIII:C<1IUdL1) to a moderate phenotype (FVIII:C1IUdL1), however, plasma FVIII:C is a poor predictor of bleeding risk. This study used thromboelastography (TEG) and thrombin generation assay (TGA) to quantify coagulation across a 48h rFVIII prophylaxis period. 10 severe haemophiliacs with varying clinical bleeding phenotypes received their standard rFVIII prophylaxis dose and blood samples were obtained over 48h. Measured parameters included FVIII:C, TEG and TGA at each time point. FVIII:C pharmacokinetics (PK) and correlation between global assay parameters was performed. The FVIII:C PK parameters were consistent with previous literature. There was significant correlation between FVIII:C and TEG R-time and aPTT (both P<0.001). Significant correlations existed between FVIII:C and TGA peak, ETP and velocity parameters (all P<0.001). At 24h the TEG parameters were sub-therapeutic despite median FVIII:C of 13.0IUdL1. TGA was sensitive to FVIII:C below 1IUdL1. Those with the severest bleeding phenotype had the lowest TGA parameters. There was significant correlation between FVIII:C and TEG and TGA. TEG lost sensitivity at 48h, but not TGA. Prospective studies are needed to determine whether these data can be used to design individualized rFVIII prophylaxis regimens.