Trends in bleeding patterns during prophylaxis for severe XXXX : observations from a series of prospective clinical trials.

@entity1 @entity2801 @entity548 @entity447
Replacement therapy or prophylaxis, has become the standard of care for the treatment of severe @entity447 . To describe bleeding patterns in @entity1 , adolescents and adults on prophylaxis and their observed relationships to times of infusion (during the week and during the day) as well as season of the year. Data from Advate pre-licensure prospective clinical trials from 145 @entity1 with @entity2801 ( @entity2801 ) <1%, were used. All @entity1 underwent a 48-h pharmacokinetic study. The 10-65 year group had >=  75 exposure days on fixed prophylaxis (25-40 IU kg(-1) 3-4x per week). Prophylaxis was not fixed but similar for 1-6 year olds. Bleeding patterns were analysed. Overall, 700 @entity548 were observed in 110/145 @entity1 . All were treated with prophylaxis, mean dose 108 IU kg(-1) week(-1) in on average 2.9 infusions (1-6 years), 86 IU kg (-1) week(-1) in 2.7 infusions (10-17 years), and 75 IU kg (-1) week(-1) in 2.6 infusions (18-65 years), respectively. On prophylaxis, median total @entity548 per year were low at 3.1 for @entity1 aged 1-6 years, 3.3 for those aged 10-17 years and 2.1 for @entity1 aged 18-65 years. @entity1 aged 1-6 years had predominantly soft tissue @entity548 (79%). Incidence of @entity548 was not associated with season, but was significantly lower in @entity1 who infused @entity2801 in the mornings: median 0 per year (IQR 0.0-0.4) compared to those who infused later [median 1.8 per year (IQR 0.0-5.2)]. Older @entity1 predominantly experienced joint @entity548 (50% and 62%, respectively). More joint @entity548 occurred during the summer [43 and 46% respectively, (P < 0.01)]. Bleeding patterns in @entity1 on prophylaxis varied according to age. In addition, the 10-65 year olds showed increased bleeding during the summer. After confirmation in prospective studies, this information may be used to improve tailoring of prophylactic treatment.
