The evidence behind inhibitor treatment with recombinant factor VIIa.

Over the past 10 years considerable use has been made of recombinant factor VIIa (rFVIIa) for the treatment of patients with inhibitors to coagulation factors. During this time, its place in the management of acute bleeds and surgery has become better defined. Although pharmacokinetic studies report the half-life of rFVIIa as 2.7 h, there is considerable intersubject variability. Moreover, rFVIIa is cleared more rapidly in children than in adults. Assays for the measurement of rFVIIa plasma levels are not readily available in clinical diagnostic laboratories, although there is evidence that plasma FVII:C levels, measured by a one-stage prothombin-based assay, reflect the plasma concentration of rFVIIa:C. The level of FVII:C required to achieve haemostasis in different clinical circumstances remains uncertain. In order to overcome the logistic difficulties of repeated frequent bolus injections, and potentially to minimise usage, administration of rFVIIa by continuous infusion has been reported. However, there is some uncertainty as to whether continuous infusion of rFVIIa has similar therapeutic efficacy to an equivalent total dose administered by bolus injections. The extensive clinical experience with rFVIIa in haemophilic patients with inhibitors has been recorded in descriptive accounts of the Compassionate Use Programme and the Emergency Use Study. On the basis of the apparent clinical efficacy and safety reported in these studies, prospective randomised trials of different dose regimens have been undertaken for the treatment of acute bleeds and surgery. These have helped to define the minimum dose needed to achieve haemostasis. There remains considerable uncertainty about the minimal effective dose and appropriate duration of therapy in different clinical circumstances. There is therefore a need for the development of evidence-based guidelines for the use of rFVIIa in bolus and continuous infusion regimens in different settings, and for the therapeutic value of measuring plasma concentrations of rFVIIa, to facilitate the optimal use of this product. Furthermore, additional randomised clinical trials will help ensure that rFVIIa is used in the most clinically and cost effective way.