In contrast, inhibitor reactivity in rFVIII concentrates varies considerably among products and shows no correlation with any particular epitope profile [25]. Thus, while epitope mapping selleck chemicals llc is unquestionably of interest, it is insufficient in itself to predict the neutralizing effect of inhibitors on various FVIII concentrates and, ultimately, the outcome of ITI therapy. The possibility also exists that other constituents in FVIII concentrates (e.g. phospholipids, FVIII fragments) and/or epitopes present in the light

chain not shielded by VWF may have a role in inhibitor reactivity [25]. Clinical data are essential to understand whether inhibitor reactivity against a specific FVIII concentrate may influence its haemostatic effect and, in turn, whether this might impact on the outcome of ITI therapy. Deeper insight into inhibitor reactivity at the clinical level is expected to assist in predicting response to ITI and improving candidate selection for ITI. To investigate the haemostatic role of inhibitor Cabozantinib ic50 reactivity variation among different FVIII concentrates, an Italian group compared inhibitor titres against a panel of FVIII concentrates

and correlated titres with the capacity to inhibit thrombin generation [26]. Inhibitor titres required to inhibit 50% of the maximum thrombin generation were lowest for rFVIII, intermediate for a purified product containing only trace amounts of VWF, and highest and similar for two VWF-containing pdFVIII (pdVWF/FVIII) (Fig. 3). Although this in vitro

study hinted that a global assay might be of use clinically to individualize treatment, the results required in vivo confirmation. This led to the design and conduct of the Predict TGA Study. The ongoing Predict TGA Study involves 20 participating centres across this website Italy. To date, 30 patients (24 with high-responding inhibitors and six with low-responding inhibitors) have been enrolled. The Predict TGA pilot study has two main objectives: To evaluate whether the thrombin generation assay can distinguish inhibitor reactivities against different FVIII concentrates (either devoid of or rich in VWF) in plasma samples from inhibitor patients (in vitro mixing experiments). To evaluate in vivo the utility of the thrombin generation assay in monitoring and detecting the haemostatic effect of FVIII concentrates in inhibitor patients. Patients with haemophilia A and inhibitors who are candidates to receive FVIII treatment are eligible for inclusion. Most eligible patients are expected to have high-responding inhibitors and receive ITI therapy. In accordance with usual practice in Italy, patients with low-responding inhibitors are to be treated with high-dose FVIII concentrates either as prophylaxis or on demand.