A correlation between thrombin generation test results and clinical bleeding phenotype has already been reported by several groups. It has been reported that patients with haaemophilia and severe clinical bleeding tendency have this website a low thrombin generating capacity (endogenous thrombin potential, ETP < 50% of normal),

independently of their fVIII/fIX levels [6–8]. A recent case-control study showed that ETP measurement in platelet-rich plasma was able to identify patients with severe haemophilia but with a mild clinical phenotype [8]. The development of an inhibitor in patients with haemophilia renders treatment and prevention of bleeding episodes more challenging. The optimal use of bypassing

agents is hampered by a lack of laboratory assays to evaluate and monitor therapeutic efficacy of these drugs and determine adequate dosing. The capability of determining most effective therapeutic option and the optimal individual dose of bypassing agents for a given patient would represent a major advance [9–12]. A recent prospective assessment of the thrombin generation test for monitoring the coagulation induced by rfVIIa and activated prothrombin complex concentrate (aPCC) showed a correlation between thrombin generating capacity and clinical outcome of patients with inhibitors in ten elective surgeries [13]. In this Erlotinib datasheet study, dose tailoring of bypassing agents was performed using a standardized three-step-protocol including (i) in vitro spiking experiments evaluating the thrombin generation ability of increasing concentrations of rfVIIa and aPCC in order to determine the minimal dose of each bypassing agent that normalizes thrombin generation capacity (Fig. 1A); (ii) ex vivo confirmation step where thrombin generation is measured before and after the administration of

the bypassing agent which fully normalized in-vitro thrombin generation (Fig. 1B) and (iii) monitoring of the chosen dose of the bypassing agent during the surgery and postoperative period (Fig. 1C). Another potential interest medchemexpress of thrombin generation measurement in haemophilia might be represented by individual tailoring of prophylaxis regimens. Two pilot studies reported promising results showing that 24 h after factor replacement therapy, patients having similar fVIII levels might have significantly different thrombin generation capacity [6,14]. Furthermore, pilot data have illustrated that the three step protocol previously used in surgical setting might be helpful to individually tailor prophylaxis regimen of patients with severe haemophilia and inhibitors [15]. However, these hypotheses need to be prospectively investigated.