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Summary Switching between different therapeutic FVIII concentrate types has been postulated as a possible cause of inhibitor development in patient with haemophilia A. In this single-centre, retrospective study, the incidence, titre and duration of inhibitor development in multitransfused patients, defined as patients with more than 150 exposure days (ED), were analysed from January 1970 to December 2007 in relation to ED and the number of switches between different products. Inhibitor titre was assessed by Bethesda assay (before 1998) or Nijmegen assay (after 1998). Medical records of 167 patients were screened, of which 97 patients met the inclusion criteria. Fourteen products of plasmatic origin (different purities) and five recombinant (three generations) were used. Nine patients (9%) developed inhibitors, all transient, low-titre (1.41 ± 0.54 BU) after 323 ± 287 ED in average. Seventeen patients had no product switches of which four patients (23%) developed inhibitors (97 ED in average), whereas 13 patients (77%) did not (ED: 230). Fifty patients switched between plasmatic products only (median: 10 changes) of which five patients (10%) developed inhibitors (ED: 503), whereas 45 patients did not (ED: 932). Five patients switched between recombinant products only (seven changes) of which no patient developed inhibitors (748 ED). Twenty-five patients switched between plasmatic and recombinant products (13 changes) of which no patient developed inhibitors (ED: 1654). No statistically significant differences between patient groups were observed. Neither the number of different FVIII products administered nor the switching of products influenced the incidence of inhibitor in multitransfused patients.

Summary. Measuring von Willebrand factor (VWF)activity is essential for the diagnosis of von Willebranddisease (VWD). The VWF activity is usually assessedbased on measurement of the ristocetin cofactor (VWF:RCo). However, that test is technically challenging andhas high intra- and inter-assay variabilities. A newautomated chemiluminescent immunoassay VWFactivity has recently become commercially available(HemosIL AcuStar von Willebrand Factor RistocetinCofactor Activity). The main objective of this study wasto evaluate this new method and to compare it with theVWF:RCo assay as the reference method. We studied91 samples, 18 healthy volunteers samples and 73samples from patients (VWF:RCo level

Head-on comparative studies of factor IX (FIX) concentrates performed under standardized conditions are rarely conducted regardless of being a valuable instrument guiding health care providers towards better informed and cost-effective decisions. This study is an extension of a multicentre study that assessed the efficacy, safety and pharmacokinetics (PK) of AlphaNine(®) in 25 previously treated patients with severe haemophilia B (FIX:C ≤ 2%). After a washout period ≥ 7 days following the last PK performed with AlphaNine(®) after a dose of 65-75 IU kg(-1) , an identical PK study was performed with BeneFIX(®) on 22 of the same patients. Venous blood samples for analysis were taken at baseline and at 0.25, 0.5, 1, 3, 6, 9, 24, 48, 72 and 74 h post infusion. The outcomes of the comparison of the PK parameters were as follows: Mean (± SD) in vivo recovery (IVR) was 1.3 ± 0.4 IU dL(-1) per IU kg(-1) for AlphaNine(®) and 1.0 ± 0.3 IU dL(-1) per IU kg(-1) for BeneFIX(®) (P < 0.01). Mean terminal half-life, mean residence time, area under the curve, clearance and volume of distribution of BeneFIX(®) were 36.0 ± 12.8 h, 39.3 ± 13.9 h, 1631 ± 467 IU h dL(-1) , 0.046 ± 0.01 dL kg(-1) min(-1) and 1.75 ± 0.52 mL kg(-1) respectively. These values were not significantly different to those observed in AlphaNine(®), although BeneFIX(®) displayed higher than expected IVR values and lower than expected clearance values. In conclusion, AlphaNine(®) showed a comparable half-life, but an IVR significantly higher than that of BeneFIX(®). This dissimilarity may have implications on dosing requirements for on-demand treatment regimes affecting optimal resource allocation.

The discrepancy of the levels of factor VIII activity (FVIII:C) by different assays in some mild and moderate haemophilic A patients has been long known. Specific mutations affecting FVIII:C discrepancies have been described. No consensus exit as to which method most accurately represents the FVIII cofactor function in vivo and which has a better correlation with the haemorrhagic clinical expression. We studied 163 mild A haemophiliacs, and detected discrepancies in 20% of the patients, most of whom presented higher levels of FVIII:C with the one-stage assay. In nine families, the FVIII mutation was found, while three showed mutations not previously described (Leu1978Phe and Ser1791Pro associated with higher levels of FVIII:C by one-stage method; Arg1639His in a patient with low level of FVIII:C by the one-stage, but normal, chromogenic assay). Assessing the level of FVIII:C by different methods could help to learn the possible haemorrhagic expressions of patients.