title: Variability of thromboelastographic responses following the administration of rFVIIa to haemophilia A dogs supports the individualization of therapy with a global test of haemostasis.
abstract: The efficacy of recombinant factor VIIa (rFVIIa) therapy in haemophilia A is challenged by the lack of a reliable monitoring tool for treatment response. This is further complicated by the significant inter-patient variability associated with this response. Thromboelastography (TEG), a real time global haemostatic test has shown superiority over conventional tests of haemostasis and has proven efficiency in the monitoring of bypass agents such as rFVIIa and FEIBA™. However, this evaluation has been limited to a few case studies or very small patient series. In this study, six severe haemophilia A dogs were treated with a clinically relevant single dose of rFVIIa, and therapy was monitored by thromboelastography predrug and at 15, 30 and 60 min postdrug administration using citrated whole blood samples activated with tissue factor and compared with non-tissue factor-activated samples. Despite the homogeneity of the tested dogs, a clear inter-individual variation was observed in the pre-and post-rFVIIa Thromboelastography analyzes. The improvement of global haemostatic parameters was seen as early as 15 min following drug administration, with a peak for factor VIIa activity in plasma at the same time. There is a significant correlation between plasma FVIIa and TEG parameters 15 min postinjection, and the baseline TEG profile influences the individual postdrug administration outcome. Together, these data support the value of TEG not only as an effective monitoring haemostatic test, but also as a tool for individualization of therapy to achieve the best haemostatic and cost effectiveness of rFVIIa therapy.
authors.affiliation: Department of Pathology and Molecular Medicine, Queen's University, and Clinical Research Centre, Kingston general Hospital, Kingston, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Othman
authors.forename: S
authors.initials: S
authors.lastname: Powell
authors.forename: W M
authors.initials: WM
authors.lastname: Hopman
authors.forename: D
authors.initials: D
authors.lastname: Lillicrap
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D004283:Dog Diseases; D004285:Dogs; D015942:Factor VIIa / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006467:Hemophilia A / Q000188:drug therapy* / Q000662:veterinary; D006487:Hemostasis / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D013916:Thrombelastography / Q000187:drug effects*
chemical_list: D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa