A comparative in vitro evaluation of seven von Willebrand factor concentrates

Abstract number: P1672

Lethagen S., Carlson M., Hillarp A.

Malmo University, Sweden

von Willebrand disease (VWD) is characterized by a deficiency of functional von Willebrand factor (VWF). The aim of this study was to evaluate the content of factor VIII (FVIII) and VWF in commercial concentrates intended for VWD. Seven concentrates from six manufacturers, Haemate P (Aventis Behring), Immunate (Baxter), Koate DVI (Bayer), 8Y (BPL), Octate (Octapharma), Innobrand (LFB) and Facteur Willebrand (LFB) were evaluated (Table 1). Large discrepancies were found between the different concentrates regarding antigen concentration, functional activity and specific activity of VWF. The specific activity (VWF activity/total protein content) varied from 4.7 to 129.5 kIU g^-1 and the ratio VWF:RCo/VWF:Ag varied from 0.19 to 0.88 in the different concentrates. There was a strong correlation between VWF antigen measured with two different assay principles (lateximmuno assay and ELISA) as well as between the two functional assays, ristocetin cofactor (RCo) and collagen binding (CB). However, the correlation between VWF antigen concentration and VWF activity was poor. The ratios VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag correlated well with the relative amount of high molecular weight multimers (HMWM) larger than the 7th multimer as determined by densitometry. In summary, our study revealed considerable differences in relative content and activity of VWF and FVIII. Concentrates lacking the HMWM are probably less efficient against mucosal bleedings as these multimers have a higher VWF:RCo and VWF:CB activity. FVIII is important for surgical bleedings, but repeated doses of a concentrate with high FVIII/VWF ratio may cause very high, pro-thrombotic FVIII levels in plasma. On the other hand, a FVIII free product may not generate sufficient FVIII levels in acute situations. It is important that the treating physicians are aware of the differences between the concentrates, and the possible clinical consequences of them.

Table 1