Recombinant wild-type GPIb has been coupled to uniform beads making the assay completely platelet free. The assay is available in two versions, one based on turbidimetric detection and the other on chemiluminescence. Recent evaluations showed that the new assay protocols were precise and suitable for diagnosis of VWD [17-19]. With

specific amino acid substitutions in the GPIb receptor it is possible to obtain constructs that bind Liproxstatin-1 research buy VWF without requiring ristocetin. With these gain-of-function GPIb peptides, novel assays, based on the ELISA format or particle-based automated assays, have been successfully developed [20, 21]. It appears, also, that activity is unaffected by a common VWF gene polymorphism known to result in false low VWF:RCo activity results [20]. An automated version of this assay type was recently commercialized and has gained popularity in regions where it has been released. According to the European external quality assessment (EQA) organization, ECAT, the number of laboratories that use a VWF:RCo assay protocol is steadily declining whereas the number using alternative activity assays is increasing. The method group for assays determining GPIb binding capacity in the ECAT programme is now divided into two activity groups: classical VWF:RCo and novel ‘VWF activity’. The current number

of participants in the two groups Navitoclax purchase is almost equal. The majority use the latex VWF activity assay, from Instrumentation Laboratory, or the Innovance VWFAc, from Siemens. PAK6 The former is not a ‘true’ activity assay as it relies on a monoclonal antibody that recognizes the functional GPIb binding epitope on VWF. However, the Innovance VWFAc assay is based on the gain-of-function GPIb construct that binds VWF without ristocetin. Despite their apparent success, based on the number of users

in various EQAs, surprisingly few independent evaluations of the novel assays have been published [22]. Compared with the VWF:RCo assay, the novel assays have several practical advantages that probably explain the rapid transition from the VWF:RCo to the novel activity assays. Moreover, the total number of users in the ECAT VWF module has increased recently and it is likely that the simplicity of the novel assays encourages less experienced laboratories to include them as the activity assay in their test repertoire. With the increased diversity of VWF activity assays, other problems arise. First, the diagnostic industry provides assays that have been developed for specific instruments that may not be available in all countries. Second, the assays themselves may not be approved for clinical use in large parts of the world. This is currently the case for the Siemens Innovance VWFAc assay, not yet approved by the US FDA. As a consequence, it is difficult to suggest general recommendations on VWD testing that include the novel activity assays.