One prospective study [42] of 19 evaluable patients has shown that patients Obeticholic Acid with severe haemophilia A (FVIII < 1 IU dL−1) and a median age of 36 years, 80% of whom had target joints at study entry, treated with 25 IU kg−1 3 days a week, had a median of 0 bleeds in 6 months compared with a median of 21 bleeds while receiving on-demand treatment. The median (inter-quartile range) FVIII trough levels measured at 48 and 72 h in these patients were

6 (1–11) and 4 (0.5–6) IU dL−1, respectively. Further studies will be required to establish whether reducing FVIII usage to target lower trough levels would have resulted in a similar reduction in bleeds. Accordingly, it is important that studies performed on young children are not extrapolated to adults. Paediatric PK data on pdFIX are conspicuously absent in the literature. Data for rFIX are available, however, for the entire age range of patients with haemophilia

B [9,37–41,43]. There was no relationship between age and terminal half-life. In addition, there were only marginal trends with age for peak and trough levels, or for dose requirements to maintain a 1 IU dL−1 trough level, during prophylactic treatment [9]. These findings contrast with those for FVIII and it would be of interest to know whether they apply also to pdFIX. Knowledge of an individual patient’s FVIII half-life is likely MS-275 mouse to be useful when prescribing a prophylactic regimen. Patients with a long half-life may respond well to being treated every third day with dose adjustment having a useful effect on the trough level. Patients who undertake relatively limited activity and/or have a mild bleeding phenotype/pattern [44] are potentially more likely to be able to tolerate the more prolonged period of time with low factor levels associated with this type of regimen. Patients with shorter FVIII half-lives will probably respond better to adjusting the frequency of dosing. Patients, for example, who are having problems with break through bleeds or target joints despite routine prophylaxis or who want to undertake Phosphatidylinositol diacylglycerol-lyase very active sports are

likely to benefit from a higher trough level. In both cases, this would be achieved more cost effectively by a period of daily dosing rather than increasing the dose on alternate days or three times a week, especially in patients with short half-lives. The benefit of frequently infused low-dose vs. intermittent high-dose FVIII treatment was recognized early [45,46]. Daily treatment, however, will not be a realistic option in many young children unless they have a central catheter. Understanding the effect of coagulation factor PK and dosing schedules also has important implications for treating patients where health care resources are limited. A low-dose daily prophylactic regimen may be possible in countries where standard regimens are too expensive.