title: ADAMTS13 content and VWF multimer and triplet structure in commercially available VWF/FVIII concentrates.
abstract: ADAMTS13 is a metalloproteinase that cleaves von Willebrand factor (VWF) into smaller multimers in vivo. This cleavage creates both the typical multimeric size distribution and the characteristic triplet band distribution of VWF. Here we analysed ADAMTS13 content, VWF multimeric size distribution and VWF triplet structure in five commercial VWF/factor VIII (FVIII) concentrates. The relative distribution of ADAMTS13 activity values corresponded well to the ADAMTS13 antigen values for all examined concentrates except Haemate HS®, which had markedly higher ADAMTS13 antigen/activity ratio, with Fanhdi® and Haemate HS® displaying the most intense ADAMTS13 signal. Interestingly, ADAMTS13 levels did not correlate with the high molecular weight multimer content of the concentrates, but did correlate with VWF triplet distribution. Densitometric quantification showed that Wilate®, Immunate® and Willfact® displayed human plasma-like VWF triplet distribution, whereas Fanhdi® and Haemate HS® showed enhanced content of the faster migrating triplet band, which corresponded well to their higher ADAMTS13 content. In summary, Immunate®, Willfact® and Wilate® had lower levels of ADAMTS13 antigen and activity and exhibited a plasma-like VWF triplet structure. Fanhdi® and Haemate HS® had higher ADAMTS13 content and an altered triplet structure. The possible impact of these observations on function and clinical efficacy of VWF/FVIII concentrates is discussed.
authors.affiliation: Octapharma Research & Development, Molecular Biochemistry Department, Berlin, Germany. Electronic address: christoph.kannicht@octapharma.com.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kannicht
authors.affiliation: Octapharma Research & Development, Molecular Biochemistry Department, Berlin, Germany.
authors.forename: Claudine
authors.initials: C
authors.lastname: Fisseau
authors.affiliation: Octapharma Research & Development, Molecular Biochemistry Department, Berlin, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Hofmann
authors.affiliation: Beuth University of Applied Sciences, Berlin, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Kröning
authors.affiliation: Octapharma Research & Development, Molecular Biochemistry Department, Berlin, Germany.
authors.forename: Birte
authors.initials: B
authors.lastname: Fuchs
mesh_terms: D051722:ADAM Proteins / Q000032:analysis*; D000071120:ADAMTS13 Protein; D005169:Factor VIII / Q000737:chemistry*; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry*; D014841:von Willebrand Factor / Q000737:chemistry*
chemical_list: D046912:Multiprotein Complexes; D014841:von Willebrand Factor; C078147:F8 protein, human; D005169:Factor VIII; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13; VWF triplets; VWF/FVIII concentrate; Wilate(®); von Willebrand factor