1). It was also introduced for ‘safety’ reasons as bleed prophylaxis after child-felt trauma (i.e. typical head trauma without bleeding signs). Prophylaxis was initiated without insertion of a Port-A-Cath after a minimal number of on-demand FVIII exposures. In patients with Everolimus research buy early joint bleeds prophylaxis was introduced at the higher frequency of 25 IU kg−1 twice a week, and in those with early severe joint or life threatening bleeds at 25–50 IU kg−1 three times a week. When required by the severity of the bleeding tendency the frequency was increased from one per week
to two per week or three per week. For tolerization (as also known from ITI programs in inhibitor patients) it seems to be important to give prophylactic FVIII doses always on the same weekday
and to avoid interrupting the prophylaxis regimen even when additional on-demand FVIII doses to manage bleeds are given. During this ‘tolerization’ period, immunological danger signals were minimized by avoiding giving first FVIII in a severe bleeding situation or during an infection, avoiding surgery during the first 20 EDs, avoiding giving vaccinations on the same day as FVIII and giving all Selleck Torin 1 vaccinations subcutaneously rather than intramuscularly. Any bleeds that did occur were treated early by giving a higher than the prophylactic dose immediately, thereby avoiding long or intensive treatment. Patients in the study group were tested for inhibitors every 3–4 EDs. Patients in the control group were treated with a standard joint-protection prophylaxis regimen of 40–50 IU kg−1 FVIII three times a week, starting at or after the first joint or other severe bleed. Please note that some of the patients in the control group (n = 8) developed their inhibitors already during on-demand therapy before they entered a standard prophylaxis program. The vaccination guidelines have been the same for both the study and the control group. Differences in inhibitor development between the study group and the historical control group were analysed by Fisher’s exact test and odds ratios (OR). The effect of potential determinants on inhibitor risk such as FVIII gene mutation
Morin Hydrate and type of product (recombinant vs. plasma-derived FVIII) was evaluated for the two groups in a logistic regression model. Differences between the two study groups of treatment-related parameters such as median EDs before prophylaxis and age at start of prophylaxis were assessed by Wilcoxon test. Fifty six of the 58 subjects studied had more than 100 EDs to FVIII therapy. Data from these were analysed for inhibitor development and both patient-related and treatment-related factors which might have affected inhibitor development. There were no significant differences between the study and control groups in any patient-related factors (Table 1), nor in the majority of treatment-related factors (Table 2). In a logistic regression model for inhibitor development with factors for study group (standard vs.