1), although therapy is often highly individualized In particula

1), although therapy is often highly individualized. In particular, the limited availability of bypassing agents or even factor concentrates in certain parts of the world may necessitate an individualized approach to management

and adaptations in haemostatic regimens, such as the intra- and postoperative use of low-dose aPCC, cryoprecipitate, or Talazoparib solubility dmso adjunctive therapies like antifibrinolytics and fibrin glue [25, 26]. The use of rFVIIa for haemostatic coverage in major and minor emergency and (mostly) elective surgeries in paediatric and adult patients with CHwI has been described in several retrospective series [6, 27-31], a recent literature review [32], and a more recent analysis by Valentino et al. of data from two prospective studies, the Hemophilia and Thrombosis Research Society registry and the literature [5]. Dosing varied substantially across these sources. In most cases, initial rFVIIa doses of 90–120 µg kg−1 were used, with a tendency towards higher initial doses for major surgeries [27-29]. Subsequent intra- and postoperative rFVIIa dosing varied and incorporated both bolus and continuous administration of rFVIIa. In some of the centres represented in retrospective case series, standardized regimens were described [6, 27]. Overall, rFVIIa was reported as

effective in the vast majority of cases encompassed by Veliparib mouse the aforementioned sources. In the analysis by Valentino et al. [5], which incorporated a small number of medical procedures (n = 45) in addition to surgical and dental procedures, rFVIIa was deemed effective in 333 (84%) of the very 395 cases represented. Thromboembolic complications attributable to rFVIIa were reported in 0.025% of procedures included in that analysis. Consensus recommendations for rFVIIa dosing for minor and intermediate or major surgical procedures in both adult and paediatric patients with CHwI have been published (Table 3) [33].

Subsequently, a consensus protocol [13] for rFVIIa dosing was devised specifically for EOS based on published data and expert opinion, incorporating recommendations for concomitant tranexamic acid dosing (Table 4), provided there are no contraindications. Satisfactory intraoperative haemostasis was achieved utilizing the higher initial rFVIIa dosing endorsed by this protocol in 13 procedures performed in five comprehensive haemophilia care centres in the United Kingdom and Ireland [13]. More recently, Caviglia et al. [34] recommended the following for optimal perioperative dosing of rFVIIa and aPCC: for rFVIIa, 120–180 µg kg−1 preoperatively followed by 90 µg kg−1 every 2 h postoperatively, and for aPCC, 100 U kg−1 preoperatively followed by 75–100 U kg−1 postoperatively, to a maximum of 200 U kg−1.

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