title: Recombinant activated factor VII for treatment of intramuscular haemorrhages: a comparison of early versus late treatment.
abstract: In the compassionate-use protocols, treatment with recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) was almost always instituted quite late, after the patient's bleeding had failed to respond to other forms of treatment. In the case of intramuscular haemorrhages, this resulted in worsening of the haemorrhage by the time treatment with rFVIIa was started. The mean number of doses given was 13.6 (64.8 for tense muscle and compartment syndrome), and 62% of episodes were judged to have an excellent or effective response. In the dose-finding study protocol, patients were required to come to the haemophilia centre for treatment, thus resulting in some delay (of at least a few hours and often longer) before rFVIIa was given. In the dose-finding study, the average time from onset of bleeding to the first dose of rFVIIa was 9 h. The average number of doses given was 3.6 for the 70 microg/kg dosage group and 3.5 for the 35 microg/kg dosage group. In contrast, patients on the US home treatment study with rFVIIa could be treated quite soon after the onset of bleeding. We have analysed the response to treatment of intramuscular haemorrhages, based on the time interval from onset of bleeding to initiation of treatment with rFVIIa. Our analysis includes cases of full-blown 'compartment syndrome', as well as other less severe peripheral intramuscular haemorrhages. The mean number of doses given was 13.6 (64.8 for tense muscle and compartment syndrome, response rated as excellent or effective in 62% of bleeding episodes) in the compassionate use study; 3.6 and 3.5 for the 70 microg/kg (72% effective) and 35 microg/kg dosage groups, respectively, in the dose-finding study, and 2.3 (92% effective) in the home treatment study. The findings clearly indicate a greater success rate, and with fewer doses, when rFVIIa was started early.
authors.affiliation: Children's Hospital of Michigan, Detroit 48201, USA. jlusher@med.wayne.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Lusher
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D015942:Factor VIIa / Q000627:therapeutic use*; D006470:Hemorrhage / Q000188:drug therapy*; D006699:Home Care Services; D006801:Humans; D008297:Male; D009132:Muscles / Q000098:blood supply*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013577:Syndrome
chemical_list: D011994:Recombinant Proteins; D015942:Factor VIIa