Increasingly, prophylaxis with bypassing therapy is being used in haemophilic patients with inhibitors . aPCC has been used as part of the Bonn ITI Protocol for more than 30 years [18,19]. In a study evaluating aPCC prophylaxis in 22 children undergoing ITI aged 0.1–6 years and with high-titre inhibitors (>5 BU mL−1), Kreuz et al. found that the median annual incidence of joint bleeding during aPCC prophylaxis (50 U kg−1 daily or 100 U kg−1 twice daily for those experiencing breakthrough bleeding) was very low (1; range, 0–6), and no patient suffered a life-threatening haemorrhage.
Moreover, no evidence of arthropathy was observed in six of eight patients evaluated radiographically, and only minimal damage was observed in the remaining two patients . Further data showing the use of aPCC as prophylaxis in ITI were reported by Valentino. In this study, three prospectively followed inhibitor patients (aged 3.7–24.1 years) were administered concomitant aPCC Selleck Small molecule library prophylaxis at a daily dose of 100 U kg−1 during ITI . Prior to initiation of aPCC, prophylaxis patients were experiencing a median of 4.1
joint bleeds per 100 days (equivalent to 15 bleeds per year); this declined to 1.4 per 100 days during LEE011 purchase treatment (equivalent to six bleeds per year). This study also showed that aPCC prophylaxis during ITI was well tolerated and no thromboses were observed . The effectiveness of aPCC prophylaxis in reducing bleeding frequency has also been investigated in patients not receiving concomitant ITI therapy. Hilgartner et al. retrospectively investigated the efficacy of aPCC 50–100 U kg−1 three to four times weekly as prophylaxis
(for 3–6.5 years) in seven patients with known long-term, high-titre FVIII inhibitors . Hilgartner et al. noted that there was a significant degree of arthropathy present in all seven patients (all had target Ergoloid joints) at the time of prophylaxis initiation. Analysis showed mixed efficacy, as two patients showed functional improvement in their arthropathy and four patients experienced a decrease in bleeding episodes. However, joint damage progressed in all target joints of these patients suggesting that prophylaxis was probably commenced too late. aPCC was also well tolerated during the study . In another retrospective analysis, Leissinger et al. evaluated five patients (aged 3–16 years), with high-titre inhibitors treated with aPCC prophylaxis (50–100 U kg−1 once daily to three times weekly) for 0.5–2 years . These data showed that aPCC prophylaxis reduced the frequency of bleeding episodes by a mean of 73–83% (see Table 1) and also maintained or improved orthopaedic status in all patients . To assess the efficacy and safety of aPCC prophylaxis, Valentino carried out a review of six studies that included a total of 34 patients . The average dose of prophylaxis used across the studies was 78.5 U kg−1, typically infused 3–4 times weekly.