Identifying haemophilia patients with inhibitors for clinical trials is difficult due to the limited number of patients available. Registries are therefore being established as an additional means of data collection. The aim of this study was to investigate the effect of different recombinant activated factor VII (rFVIIa; NovoSeven dose ranges and dosing schedules on the incidence of re-bleeding in haemophilia patients with inhibitors. In this retrospective, uncontrolled study, data on the bleeding patterns of adult haemophilia patients with high responding inhibitors were analysed. Only data from the Czech Republic, obtained by the HemoRec registry, were used. This study analysed 'real-life' clinical data and focused on the collection of the same parameters in different patients: time from bleeding onset to first injection, effect of first injection, number of re-bleedings, total number of injections and total amount of haemostatic drug used. Fifteen patients met the inclusion criteria and were included into the study (128 bleeding episodes). Patients treated within 2 h of bleeding onset experienced less re-bleeding than patients treated after 2 h of bleeding onset (5.2% vs. 13.7%, respectively). In addition, patients who were treated after 2 h of bleeding onset experienced fewer re-bleedings when high-dose rFVIIa was used (15.8% and 0%; <120 microg kg(-1) and >250 microg kg(-1), respectively). Initial high-dose rFVIIa was also associated with a decline in total rFVIIa consumption. This registry has provided a unique insight into the bleeding patterns of inhibitor patients, highlighting the importance of early treatment initiation and appropriate starting dose.

RCo and HemosIL are ristocetin dependent, whereas INNOVANCE does not rely upon ristocetin and is not influenced by VWF polymorphisms increasing VWF:GPIb-binding activity levels. INNOVANCE seems to be the best choice as a first-line VWF:GPIb-binding activity assay, providing the best balance between sensitivity and specificity for type 2 VWD.

Background von Willebrand disease (VWD) is an inherited bleeding disorder caused by a quantitative (type 1 and 3) or qualitative (type 2) defect of von Willebrand factor (VWF). The heterogeneity of laboratory phenotyping makes diagnosing difficult. Objective A cross-sectional, family-based VWD study in a collaboration between University Hospital Brno (Czech Republic) and Antwerp University Hospital (Belgium) to improve the understanding of laboratory phenotype/genotype correlation. Patients and Methods A total of 205 patients with suspected VWD were identified from historical records. Complete laboratory analysis was established using all available VWD assays including VWF multimers and genetic analysis. Results Based on the current International Society of Thrombosis and Haemostasis (ISTH) – Scientific and Standardization Committee VWD classification and type 2A sub-division into 2A/IIA, IID, IIC and IIE, the majority was characterized as a type 1 VWD, followed by type 2. Proposed laboratory phenotypes were confirmed by their multimeric pattern within 98% of this cohort. All type 2, 3 and 75% of type 1 VWD patients were confirmed by underlying causative mutations. Forty-six different causal mutations (117 not previously described in the literature) could be identified. Fifty per cent of all cases was represented by eight individual mutations, mainly p.Pro812ArgfsX31. Thirteen patients had a large heterozygous gene alteration. Conclusion Although an extensive panel of tests was used, VWD classification and (sub)typing remains difficult and fluid. This study provides a cross-sectional overview of the VWD population in the Czech Republic and provides important data to the ISTH/European Association for Haemophilia and Allied Disorders VWD mutation database in linking causal mutations with unique VWD (sub)types. It also identifies new, as not previously described in the literature, causal mutations.

This study is registered under the identifier NCT04832841 on ClinicalTrials.gov.