Recombinant, activated factor VII for surgery in factor VII deficiency: a prospective evaluation – the surgical STER

Abstract

SummaryExcessive bleeding represents a major complication of surgical interventions and its control is especially relevant in patients with Congenital Bleeding Disorders (CBD). In factor VII (FVII) deficiency, scanty data on surgery is available to guide treatment strategies. The STER (Seven Treatment Evaluation Registry) is a multi-centre, prospective, observational, webbased study protocol providing the frame for a structured and detailed data collection. Inhibitor occurrence was checked in a centralized fashion. Fortyone surgical operations (24 'major' and 17 'minor') were performed in 34 subjects with a carefully characterized FVII deficiency under the coverage of recombinant activated Factor VII (rFVIIa). Bleeding occurred during three major interventions of orthopaedic surgery, but rFVIIa was given at very low dose in each case. An antibody to FVII was observed in one patient who underwent a multiple dental extraction. No thromboses were reported during the 30-d follow up period. Replacement therapy with rFVIIa proved effective when suitable doses were used, which, during the period of maximum bleeding risk (the day of operation), were calculated (Receiver Operated Characteristic analysis) to be of at least 13 lg/kg/body weight per single dose and no less than three administrations. This indication is important especially in the case of major surgery.

Women with congenital factor VII deficiency: clinical phenotype and treatment options from two international studies

“…As bleeding complications only occurred during the first 24 postoperative hours and baseline FVII:C levels did not help to predict bleeding (all <1%), the analysis restricted to the early RT period showed that nonbleeders were given a higher first dose (at least 22 µg/kg) and no less than two doses in comparison to those patients who had bled. These findings highlight the importance of using a sufficiently effective RT schedule during the first 24 postoperative hours to prevent postoperative bleeding [26,27].…”

Prophylaxis in congenital factor VII deficiency: indications, efficacy and safety. Results from the Seven Treatment Evaluation Registry (STER)

“…6 In our cohort, despite the large number of infusions, no thrombotic events of any kind were reported during the follow-up period, either in adults or elderly patients, a finding consistent with the experience reported in a recent surgical study of FVII-deficient patients. 41 Limitations to our study include the efficacy evaluation performed by the investigators, the retrospective part of the follow-up and also the small number of patients, which may have hampered a more precise definition of the efficacy of the prophylactic schedule. Nevertheless, for the patients with "excellent" results, no breakthrough bleeding episodes were reported in the database, in contrast to the less favorable outcomes in which bleeding episodes were reported.…”

Management of Arthropathy in Moderately Deficient Factor VII Patients: Results From Hospital Developed Treatment Protocol

“…These results were not different significantly from the other studies conducted. In one article, it is stated that two patients with FVIId underwent hip and knee replacement surgery and total dose of rFVII administered was 263 and 241 IU/kg, respectively [9]. Our patients received a much higher dose than the above mentioned study, i.e.…”

“…Mean dose/procedure ranged from 13.85 to 26.29 μg/kg and the number of doses/procedure varied from 30 to 112. Other results from different groups showed that 20 -25 μg/dL of rFVII should be given at every 4 -6 h in combination with tranexamic acid which was seen to be effective in surgical settings for FVIId patients but treatment duration is not well defined [5,8,9,15]. Pharmacokinetic studies of rFVII helped in choosing the dose and time interval between the subsequent infusions, but it is still not defined about minimum requirement for FVII in plasma to attain hemostasis [15,16].…”

“…Even though rFVII is widely used in FVIId patients, there is scarce of literature for treatment patterns in FVIId patients with surgical intervention [5,9]. The main objective of our study was to give a result of the treatment protocol for FVIId patients undergoing orthopedic surgery in our hospital (Table 1) and compare its results with other studies conducted around the world.…”