Background: VWF-containing concentrates from human plasma (pdVWF) vary in the content
and composition of VWF, FVIII and other constituents. rVWF (vonicog alfa, Baxalta US Inc., a Takeda company, Lexington, MA, USA) is a highly purified VWF protein produced in CHO cells. In contrast to any pdVWF, rVWF maintains an intact multimer pattern because it is never exposed to proteolytic degradation, particularly not by the VWF cleaving protease ADAMTS13. Although some comparisons of pdVWF and rVWF are published, a comprehensive analysis of multimers and functional characteristics of VWF products is lacking.

Aims: Structural and functional comparison of clinically used pd and rVWF concentrates:

• pdFVIII/VWF: HAEMATE P/HUMATE-P, VONCENTO (CSL Behring, King of Prussia, USA); WILATE/EQWILATE (Octapharma, Lachen, Switzerland)
• pdVWF: WILFACTIN/WILLFACT (LFB, Courtaboeuf, France)
• rVWF: VONVENDI/VEYVONDI

Methods: Cross-product comparisons included VWF content by determination of VWF:Ag, and biological function assessed by VWF:RCo, VWF:CB, and VWF:GpIbM (VWF activity assay Innovance; Siemens) using routine commercial test kits. VWF multimeric structure was determined by low (1 %) and high (2.5 %) resolution agarose electrophoresis.

Results: In all pdVWF concentrates the ratio between measurements of biological function of VWF and VWF:Ag content was below 1, indicating the presence of not fully active VWF between 5 and 30%. Corresponding ratios for rVWF were above 1. Thus, rVWF has higher specific activity by all biological measurements. Only rVWF contained the full spectrum of ultra-large and high molecular weight multimers (Figure 1). While pdVWF showed varying satellite band structures indicative for different degrees of proteolysis, rVWF had an intact multimeric pattern. VWF:GpIbM measurements were, for all products, higher than those obtained with the VWF:RCo assay.

Conclusions: VWF products differ in their contents, multimer size and structure of functional VWF. These differences may translate into improved biological activity of rVWF in clinical settings and influence the treatment regimen of individuals with VWD.

[Figure 1. Low resolution (1%) agarose electrophoresis of rVWF and pdVWF concentrates]

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/recombinant-human-von-willebrand-factor-rvwf-differs-in-structure-and-function-from-plasma-derived-concentrates/