Monitoring rFVIII prophylaxis dosing using global haemostasis assays


Correspondence: Dr. Donald F. Brophy, Virginia Commonwealth University, PO Box 980533, Richmond, VA 23298-0533, USA.

Tel.: +1 804 828 8367; fax: +1 804 828 0343;



Secondary factor VIII (FVIII) prophylaxis converts severe haemophiliacs (FVIII:C < 1 IU dL−1) to a moderate phenotype (FVIII:C ≥ 1 IU dL−1), 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 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 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 24 h the TEG parameters were sub-therapeutic despite median FVIII:C of 13.0 IU dL−1. TGA was sensitive to FVIII:C below 1 IU dL−1. 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 48 h, but not TGA. Prospective studies are needed to determine whether these data can be used to design individualized rFVIII prophylaxis regimens.