In general, initial doses of 50–100 U kg−1 were given prior to surgery, either as a single dose or as multiple doses in the days or hours preceding surgery. Subsequent aPCC doses

totalling up to 200 U kg−1 day−1 were administered beginning 6–8 h after surgery at 6- to 12-h intervals for variable durations of time. Consensus recommendations for aPCC dosing for both major and minor surgeries have been developed (Table 3) [33]. Criteria for satisfactory haemostasis were met in 80% or more of cases in each of the aforementioned series. There was a single thromboembolic event reported across more than 170 surgeries in the combined series. The sequential or combined use of rFVIIa and aPCC for haemostatic coverage during surgery and

the early postoperative period has also been described in patients buy Erlotinib with CHwI [35, 40]; in some cases, this strategy was adopted due to prior clinical response to one or both bypassing agents or bleeding complications relative to the current surgery [35, 40], while in others, patients were switched to aPCC after initial coverage with rFVIIa because of cost [35]. With combined therapies, one should be cautious about the occurrence of thromboembolic events [40], although none have been reported in patients with CHwI undergoing surgery. Although not available at all institutions, preoperative evaluation of haemostatic response to bypassing agents using thrombin generation testing (TGT) or thromboelastography (TEG) has been proposed as a means to optimize the haemostatic 上海皓元 management of individual patients with inhibitors for surgery [13, 41]. In a small prospective Selleck Stem Cell Compound Library study of 10 surgeries in patients with inhibitors, in vitro and ex vivo TGT were used to assess the dose-dependent haemostatic response to each bypassing agent preoperatively; TGT was then used intra- and postoperatively to monitor the response to haemostatic therapy, which was selected based on the preoperative TGT results [41]. Thrombin generation correlated with clinical haemostasis in this study, and preoperative TGT results were generally predictive of perioperative haemostatic response. Thromboelastography was similarly used to guide rFVIIa therapy

in a patient with CHwI undergoing urgent evacuation of a spinal cord haematoma [42]. Although these preliminary findings suggest the potential utility of these techniques for optimizing haemostatic therapy in individual patients with CHwI undergoing surgery, further study and validation are needed before they can be more widely adopted for this purpose [13, 41]. Preoperative planning of haemostatic coverage for surgery should incorporate a strategy for monitoring haemostatic response during surgery. However, this poses a challenge in CHwI as the major drawbacks of rFVIIa and aPCC are their unpredictable haemostatic effect, lack of laboratory assays to monitor efficacy and dosing frequency, as well as the potential risk of thrombosis.