An even higher dosing regimen has been proposed [49], with a preoperative bolus of 120–180 μg kg−1, followed by doses of 90 μg kg−1 at 2 h intervals for the next 48 h, thereafter the intervals being increased to 3, 4 then 6 h on days 3, 5 and 8, respectively, and continued this website until discharge. For those preferring continuous infusion, a 50 μg kg−1 h−1 dosing was suggested

[48] based on a prospective study [50]. Some authors prefer bolus dosing because they believe that the burst of thrombin generation achieved is important for haemostasis [51]. There are less data available for surgeries performed with FEIBA compared to rFVIIa. The publications from single institutions, national or international cohorts reported

mainly minor surgeries and a limited number of major procedures [52–56]. Usually a first dose of 50–100 U kg−1 per dose is given 1 h before the surgery and is repeated every 6–12 h for a maximum daily dose of 200 U kg−1 and tapered until discharge. The ongoing SURgical Interventions with FEIBA (SURF) open-label, prospective, non-interventional, post-authorization safety surveillance study has already recorded 13 major surgeries of a total of 35 procedures and will further increase this experience [57]. Globally, rFVIIa or APCC secured haemostasis safely in different types of elective or emergency minor and major surgeries, in adult and paediatric patients with inhibitors. Comparison of efficacy is difficult selleck compound due to the variety of treatments, the different definitions for minor or major surgery and the diverse modalities for evaluation of success. For surgery, no comparative studies between the two products have been carried out. The absence of objective evidence of differences in the relative responsiveness and safety, has led to a recommendation of both agents equally [5]. However, in 2008, a MEDLINE search indicated that 82% of AMP deaminase major procedures were covered with rFVIIa and 71% of the minor procedures were performed with APCC [58]. Despite a twofold to fivefold increase in the cost concentrate to cover surgery with bypassing agents compared

to non-inhibitor patients [53,59,60], outcomes were not always favourable. Indeed, discordant responsiveness to both agents has been described, including some patients treated with high doses, pointing out the inter-individual variability of efficacy [58,61]. Bleeding complications remained more frequent in inhibitor (2/7, 28%) than in non-inhibitor patients (2/109, 2%; P < 0.05) in a retrospective study of outcome of 116 primary total knee replacements (TKR). Inhibitor was also a risk factor for infection as inhibitor was present in 3/9 patients with TKR infection (33%) and 4/83 patients without TKR infection (5%; P < 0.05) [62]. Insufficient correction of haemostasis may indeed increase angiogenesis and induce delayed wound healing [63].