The pharmacokinetics and pharmacodynamics of single‐dose and multiple‐dose recombinant activated factor VII in patients with haemophilia A or B

Summary Monitoring recombinant activated factorVII(rFVIIa) treatment outcomes remains challenging. Thromboelastography (TEG) and the thrombin generation assay (TGA), measure coagulation dynamics over time and are being assessed as potential methods for evaluating and monitoring haemophilia treatment. Lack of standardizedTEG/TGAmethods makes it difficult to compare results and to establish a correlation with clinical outcomes. Aims To compare the pharmacokinetics (PK) ofrFVIIa after 3×90 μg kg−1doses vs a single dose (270 μg kg−1) in haemophilia patients and to evaluateTEG/TGAresults postdosing to determine how these assays relate toPKfindings. Methods Patients in this open‐label, single‐centre, randomized, crossover trial received one injection of 270 μg kg−1rFVIIa crossed over with three injections of 90 μg kg−1rFVIIa in a non‐bleeding state. ForTEG, kaolin and tissue factor were used as activators;TGAwas performed on frozen platelet‐rich and platelet‐poor plasma, with and without corn trypsin inhibitor.FVIIa activity was evaluated using in vivo samples. Results TGAshowed a dose‐dependent effect ofrFVIIa on thrombin generation;TEGrevealed lower dose‐dependent effects. Both showed some differences between single‐/multiple‐doserFVIIa; both supported thePKfindings. Conclusion WhileTEGandTGAare not yet clinically predictive, both supported thePKresults. Data suggest that, while a single dose of 270 μg kg−1rFVIIa provides slightly higher haemostatic potential than the multiple‐dose regimen of 3×90 μg kg−1, the latter results in prolonged activity levels compared with a higher single dose.