Expression in COS-1 cells indicated that the mutant protein is poorly secreted and not functional. In conclusion, the c.1281C>G mutation, which was predicted to be translationally silent and hence neutral, causes FV deficiency by impairing pre-mRNA splicing. This finding underscores the importance of cDNA analysis for the correct assessment of exonic mutations. “
“Clotting factor replacement therapy, while highly effective in controlling bleeding in patients with hemophilia, is hampered by the formation of inhibitory antibodies and a c-Met inhibitor relatively

short duration of hemostatic activity. An important focus of current hemophilia research is the development of less immunogenic and more potent and/or longer-acting factor concentrates. “
“A Post-Authorization Safety Study (PASS) global program was designed to assess safety and effectiveness of rAHF-PFM (ADVATE) use in haemophilia patients in routine clinical settings. The main aim of this project was to estimate the rate of inhibitors DAPT and other adverse events across ADVATE-PASS studies by meta-analysing individual patient data (IPD). Eligible Studies: PASS studies conducted in different countries, between 2003 and 2013, for

which IPD were provided. Eligible patients: haemophilia A patients with baseline

FVIII:C < 5%, with a known number of prior exposure days (EDs). Primary outcome: de novo inhibitors in severe, previously treated patients (PTPs) with > 150 EDs. Secondary outcomes: de novo inhibitors according to prior exposure and MCE disease severity; other adverse events; annualized bleeding rate (ABR). Analysis: random-effects logistic regression. Five of seven registered ADVATE-PASS (Australia, Europe, Japan, Italy and USA) and 1188 patients were included (median follow-up 384 days). Among severe PTPs with > 150 EDs, 1/669 developed de novo inhibitors (1.5 per 1000; 95% confidence interval [CI] 0.2, 10.6 per 1000). Among all patients included in the PASS studies, 21 developed any type of inhibitors (2.0%, 95% CI: 0.8%, 4.7%). Less than 1% of patients presented with other serious adverse events possibly related to ADVATE. The overall median ABR was 3.83 bleeds/year (first, third quartiles: 0.60, 12.90); 1.66 (0, 4.78) in the 557 patients continuously on prophylaxis ≥ twice/week. Meta-analysing PASS data from different countries confirmed the overall favourable safety and effectiveness profile of ADVATE in routine clinical settings.