title: Monitoring rFVIII prophylaxis dosing using global haemostasis assays.
abstract: 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.
authors.affiliation: Coagulation Advancement Laboratory, Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, VA 23298-0533, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Al Hawaj
authors.forename: E J
authors.initials: EJ
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Venitz
authors.forename: J C
authors.initials: JC
authors.lastname: Barrett
authors.forename: J G
authors.initials: JG
authors.lastname: Kuhn
authors.forename: M E
authors.initials: ME
authors.lastname: Nolte
authors.forename: D F
authors.initials: DF
authors.lastname: Brophy
mesh_terms: D000328:Adult; D001780:Blood Coagulation Tests; D005169:Factor VIII / Q000032:analysis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006467:Hemophilia A / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis / Q000493:pharmacokinetics; D013916:Thrombelastography; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; D005169:Factor VIII; D013917:Thrombin