These adjustments can be informed, and potentially made more cost-effective, by pharmacokinetic measurements. For example, if a person on prophylaxis has had no Trichostatin A breakthrough bleeds and their trough level is measured at 6 IU dL−1, then their dose of FVIII/FIX could be halved and their trough would still be 3 IU dL−1, if the dose is cut by 66% the trough would be 2 IU dL−1. Although this may not need to be considered in a country with an unlimited supply of concentrate,
in countries with limited health care resources, the saved concentrate could allow another one or two people to be started on prophylaxis. If an individual has a target joint, then a period of more intensive prophylaxis that sustains a higher trough can be tried. Once the joint has settled, the regimen can be reduced. If bleeds occur in relation to a specific activity, the timing of the infusions can be adjusted to provide better cover. Regimen may be better adjusted, if pharmacokinetic data are available that give information about the factor level at the time of the break-through bleeds or anticipated activity. It is common practice
to infuse prophylaxis on a Monday, Wednesday and Friday and FIX twice a week. This has the disadvantage of allowing periods with low levels, and potentially increases the risk of break-through bleeds. Giving an increased dose of FVIII on a Friday is a common practice, but to cover the extra day a fourfold increase is required MCE公司 (Fig. 2). A more cost-effective strategy, and one that results in substantially better factor levels, is to give an extra, lower dose, infusion on Saturday or Sunday, depending on when the most activity Selleckchem LY294002 is anticipated (Fig. 3). Infusing
on alternate day avoids this problem and some families find this an easy regimen to follow. The choice of which regimen to use is individual, and often depends on what the patient is used to, in our experience, if alternate prophylaxis is started at a young age, then there are very few problems with adherence. Increasing the frequency of FVIII/FIX infusions can be used to maintain a desired trough level whilst using substantially less FVIII/FIX or to allow a much higher trough to be achieved with the same amount of concentrate (Fig. 3). In haemophilia B, for example, to maintain a trough FIX level above 1 IU dL−1 treating 1–3 times a week, every third day or on alternate days takes an average of 240 000, 137 000 and 108 000 IU year−1 respectively [22]. Similar effects are seen by increasing the frequency of FVIII infusions [23]. An important potential advantage of more frequent dosing is that, by using less concentrate, more people with haemophilia can have access to treatment. For example, in a 70 kg adult with an average FVIII half-life, the baseline FVIII can be maintained above 1 IU, with 100 IU day−1, 36 500 IU year−1 compared with standard weight-based dosing of 110 000 IU year−1 [14].
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