title: Management and monitoring of recombinant activated factor VII.
abstract: Recombinant factor VIIa (rFVIIa) has recently been introduced as a new 'bypassing' agent to improve haemostasis in haemophilia patients with inhibitors to factor (F) VIII or FIX. In noninhibitor patients, levels of circulating FVIII or FIX can be used to assess the quality of substitution therapy. In contrast, laboratory monitoring of haemostatic efficacy in patients treated with rFVIIa has proved more complex. Evaluation of patient samples saved during rFVIIa treatment have revealed some correlation between FVII:C levels and improved haemostasis, while whole blood elasticity, as determined by thromboelastography, has been shown to improve following rFVIIa treatment. The investigation aimed to study the efficacy of rFVIIa in activating FX:C and in shortening the whole blood clotting time (WBCT) using the newly-developed roTEG coagulation instrument. Results indicated a substantial and apparently dose-dependent activation of FX:C by rFVIIa. In addition, the presence of FIX appeared to influence FX:C activation. In-vitro and ex-vivo roTEG thromboelastograph measurements showed that FVIIa shortened WBCT, although normalization did not occur. The results presented here are based on a small number of observations in a few patients and further studies should be planned to test the efficacy of these monitoring principles in clinical treatment practice with rFVIIa.
authors.affiliation: Department of Clinical Immunology, Centre for Haemophilia and Thrombosis, Aarhus, Denmark. j-ing@post3.tele.dk
authors.forename: J
authors.initials: J
authors.lastname: Ingerslev
authors.forename: K
authors.initials: K
authors.lastname: Christiansen
authors.forename: A
authors.initials: A
authors.lastname: Calatzis
authors.forename: M
authors.initials: M
authors.lastname: Holm
authors.forename: L
authors.initials: L
authors.lastname: Sabroe Ebbesen
mesh_terms: D001760:Bleeding Time; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D015942:Factor VIIa / Q000008:administration & dosage*; D005170:Factor X / Q000378:metabolism; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D011486:Protein C / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D011486:Protein C; D011994:Recombinant Proteins; D005170:Factor X; D015942:Factor VIIa