Analysis of data from the Haemophilia and Thrombosis Research Society (HTRS) Registry was performed on episodes where doses of ≥250 μg kg−1 were reported. From 2041 rFVIIa-treated bleeds, 172 bleeding episodes were identified in 25 individuals with CHwI who were treated with ≥1 higher doses (≥250 μg kg−1, ≥270 μg kg−1
or ≥300 μg kg−1) of rFVIIa between January 2004 and November 2008. Bleeds occurred in individuals ranging in age from 0.4 to 41.7 years who were predominantly non-Hispanic and white (40%) with haemophilia Doxorubicin A (88%). Bleed types most frequently treated with higher doses of rFVIIa were spontaneous (62–65%) or traumatic (27–32%). Bleed locations most frequently treated with higher doses of rFVIIa were joint (60–68%) or muscle (20–25%). A total of 1521 rFVIIa doses were administered (median, three doses per bleed); 26% were 250 μg kg−1 or higher (initial dose, 82%). Bleeding stopped in 93% (160/172) of bleeds treated with rFVIIa 250 μg kg−1 or higher. No serious adverse drug-related events or thrombotic complications were reported. This data
analysis from the HTRS Registry provides evidence of the safe and effective use of higher doses of rFVIIa (≥250 μg kg−1) in US practice. “
“Summary. The most problematic complication of haemophilia A treatment is the development of inhibitors Selleck Z-VAD-FMK to FVIII. The highest risk of developing inhibitors is during the first 20 exposure days (EDs). If the patient can be brought through this high risk period without inhibitor development, the subsequent risk is low. Therefore, as a pilot project, we developed a prophylaxis regimen for the first 20–50 EDs specifically designed to induce tolerance to the administered FVIII and to minimize
inhibitor development by avoiding immunological danger signals. Twenty-six consecutive previously untreated patients (PUPs) with severe haemophilia A were treated with the new prophylaxis regimen and the incidence of inhibitor development in this group was compared with that in a historical control group of 30 consecutive PUPs treated N-acetylglucosamine-1-phosphate transferase with a standard joint protection prophylaxis regimen (40–50 IU kg−1, three times a week). There were no significant differences between the study and control groups in patient-related inhibitor risk factors such as ethnicity (all Caucasian), severity of haemophilia (all <1% FVIII), severity of FVIII gene mutation (P < 0.0006) nor in some treatment-related factors such as product type, age at first exposure, vaccination regimen or the need for surgery. 14 of 30 subjects given standard prophylaxis but only one of the 26 subjects given the new regimen developed an inhibitor (P = 0.0003, odds ratio 0.048, 95% CI: 0.001–0.372). Our results indicate that minimizing danger signals during the first 20 EDs with FVIII may reduce the risk of inhibitor formation. These results should be confirmed in a larger prospective clinical study.