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

Summary.  Replacement therapy or prophylaxis, has become the standard of care for the treatment of severe haemophilia A. To describe bleeding patterns in children, 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 patients with factor VIII (FVIII) <1%, were used. All patients 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 bleeds were observed in 110/145 patients. 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 −1week−1 in 2.7 infusions (10–17 years),and 75 IU kg −1week−1 in 2.6 infusions (18–65 years), respectively. On prophylaxis, median total bleeds per year were low at 3.1 for patients aged 1–6 years, 3.3 for those aged 10–17 years and 2.1 for patients aged 18–65 years. Patients aged 1–6 years had predominantly soft tissue bleeds (79%). Incidence of joint bleeding was not associated with season, but was significantly lower in patients who infused FVIII 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 patients predominantly experienced joint bleeds (50% and 62%, respectively). More joint bleeds occurred during the summer [43 and 46% respectively, (P < 0.01)]. Bleeding patterns in patients 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.