The benefits of prophylaxis in haemophilia have been demonstrated repeatedly. Prevention of bleeding and arthropathy [10, 11], better quality of life [16, 17], fewer school absences and higher academic achievement in young school-age children have been documented [18]. Importantly, children with VWD in a Swedish

cohort who started prophylaxis early never developed joint disease [12]. A few additional investigations have been reported using different VWF-containing concentrates [19, 20], [21, 22]. Common among these was the finding that prophylaxis appears to be effective at decreasing or eliminating bleeding, and that side effects are mild. No cases of thromboembolism have been reported. click here In the Swedish cohort, one patient developed an inhibitor. In a recent publication from Germany, a retrospective study of 32 patients was reported. Following a 12-month period, the monthly bleeding frequency was significantly reduced compared with the preprophylaxis values (3 vs. 0.07), and an Everolimus in vivo inhibitor developed in one patient. Allo-antibodies against VWF are a rare complication of treatment with plasma-derived concentrates containing VWF [23]. They usually occur in type 3 VWD characterized by large deletions

of the VWF gene; however, there are currently no data regarding the clinical and molecular markers of these complications. In particular, there is no evidence that prophylaxis with VWF concentrates triggers their appearance as in almost all cases reported, the antibodies developed during on-demand treatment. In this study, the effect of prophylaxis appeared to be most pronounced in the case of joint bleeding, as has been observed in other investigations [12]. Joint haemorrhage occurs when FVIII levels are low. Haemarthroses are prevented primarily by the increase in FVIII levels during prophylaxis and not impacted by the VWF levels, per se. Mucosal bleeding, i.e. epistaxis, GI bleeding

and menorrhagia, was reduced but not to the same degree, perhaps because these haemorrhages are not only dependent on normal circulating levels of active VWF, but also on the presence of discrete concentrations Meloxicam of normal VWF inside the platelets and within endothelial matrices. These considerations of the biology and physiopathology of VWF should be kept in mind when therapeutic approaches are chosen to stop or prevent mucosal bleeding, especially in patients with VWD types 3 or 2A, which are characterized by absent or abnormal VWF in platelet and endothelial sites. In ex vivo experiments, the lack of normal platelet VWF was reported to be the major factor for impaired platelet adhesion to subendothelium in patients with VWD types 3 and 2A [24]. More importantly, when patients with VWD type 3 were given large doses of cryoprecipitate containing all the VWF multimers, all could correct VWF:RCo whereas 60% still showed prolonged bleeding time (BT), the surrogate marker of the cellular defect of VWF at the vascular sites.