rFIX, on the other hand, should not be given with longer dosing intervals than 3 (or preferably 2) days due to its higher CL and shorter terminal half-life [9]. If studies confirm that it is appropriate to target specific trough levels, which are likely to vary between patients and across time in an individual, then knowledge of a patient’s coagulation factor PK is necessary for this to be done effectively. Direct measurement of a trough level may be inconvenient

to the patient and is technically more demanding, as measuring low FVIII/IX levels is associated with a wider variance in the assay and single measurements are more prone to error. Furthermore, if the level is below 1 IU dL−1, no information U0126 solubility dmso is gained and the dose cannot be adjusted to target a desired level. PK estimated by Bayesian analysis Torin 1 clinical trial from suitable FVIII/FIX data points well above the baseline provides a coagulation level vs. time curve from which the trough level can be predicted [20]. Thus, a dose that targets a specific level can be calculated with more confidence. Although a trough level of 1 IU dL−1 is often recommended for patients on prophylaxis, in many cases, this is unlikely to be appropriate. Patients may be adequately treated despite a trough level below 1 IU dL−1 or require a level above 1 IU dL−1 to prevent bleeds. Very few data are available

on appropriate trough levels in different patients and clinical situations. Higher levels are likely to be required

to suppress target joints or to cover high levels of physical activity than to prevent bleeds in quiescent joints. The effect that the same level of FVIII and IX has in correcting global haemostasis clinically is also unclear, but may well be different. Once an appropriate trough level is decided, the dose of concentrate required to maintain this level is straightforward to calculate because the trough is directly proportional to the dose. For example, if a patient has a trough level of 2 IU dL−1 and the required trough is 4 IU dL−1, then the dose needs to be doubled, whereas if the desired trough is 1 IU dL−1, the 上海皓元医药股份有限公司 dose needs to be halved. If tailoring prophylaxis to target a specified trough level is shown to be efficacious, then a consequence would be the need for smaller vials of concentrate to allow more flexible dosing. This is particularly the case in children or adults on daily regimens. The recent trend towards higher dose vials tends to have the effect of increasing the amount of coagulation factor used during prophylaxis, and the increased cost of patient convenience of using one vial rather than two may be hard to justify. The concepts discussed in this review are based on a number of hypotheses that, although plausible, need to be confirmed in prospective studies. It will need to be established whether dosing patients to a predetermined trough level leads to adequate bleed prevention.