Monitoring rFVIII prophylaxis dosing using global haemostasis assays.

ABSTRACT

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