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The Super Glue of Ultra-Large Multimers – Characterisation of Recombinant and Platelet Derived von Willebrand Factor

T. Kragh1, M. Spannagl1, H.W. Ott2, P. Möhnle1,3, I. Pekrul1,3

1Ludwig-Maximilians-University Munich, Transfusion Medicine, Cell Therapeutics and Haemostaseology, Munich, Germany, 2Labor Augsburg MVZ GmbH, Augsburg, Germany, 3Ludwig-Maximilians-University Munich, Anaesthesiology, Munich, Germany

Abstract Number: PB1529

Meeting: ISTH 2020 Congress

Theme: Platelet Disorders and von Willebrand Disease » von Willebrand Factor Biology

Background: The multimeric composition of recombinant von Willebrand factor (rVWF) concentrate as well as platelet VWF (plateletVWF) is different compared to plasma-derived VWF (pdVWF). rVWF as well as plateletVWF retain full-spectrum multimers with a higher proportion of ultra-large multimers (ULM).

Aims: We aimed to characterize and compare structural and functional properties of plateletVWF, pdVWF, and rVWF.

Methods: pdVWF was obtained from whole blood of 10 healthy volunteers and plateletVWF was isolated after centrifugation, two washing steps and application of detergent. Two approved and commercially available plasma derived VWF concentrates and a recombinant VWF were tested. Standard assays (IL Instrumentation Laboratory, Bedford, MA, USA) for 1) VWF:Ag, 2) VWF:GP1bM, and VWF:GP1bR, 3) VWF:CBA were used. Gel electrophoresis served for multimeric analysis.

Results: For optimized comparability VWF measurements were standardized for VWF:Ag (=100%). Results for VWF:Ag and activity parameters are shown in table 1 and 2. Multimer analysis showed the previously described structural differences with both rVWF and plateletVWF containing a high portion of ultra-large multimers (plateletVWF >rVWF>pdVWF) and the absence of triplet bands compared to pdVWF or pdVWF concentrates.

  VWF:Ag VWF:GP1bM VWF:GP1bR VWF:CBA
pdVWF concentrate 1 100 71 82 58
pdVWF concentrate 2 100 70 78 50
rVWF concentrate 100 120 105 110

[Table 1: Analysis of commercial VWF products (measured in duplicates).]

  VWF:Ag VWF:GP1bM VWF:GP1bR VWF:CBA
plateletVWF 100 ± 21 142 ± 44* 46 ± 8* 72 ± 15*
pdVWF 100 ± 36 90 ± 39 81 ± 34 99 ± 29

[Table 2: Analyses of pVWF and pdVWF from healthy donors (n=10; mean ± SD). * denotes statistically significant difference to pdVWF.]

Conclusions: Significant functional and structural differences between plasmatic, platelet and recombinant VWF could be demonstrated. Importantly, the rVWF preparation clinically used as an equivalent of the plasmatic VWF, shows partial structural and functional similarities to plateletVWF with comparable values of activity parameters and multimeric structure potentially implying improved hemostatic efficacy compared to pdVWF.

To cite this abstract in AMA style:

Kragh T, Spannagl M, Ott HW, Möhnle P, Pekrul I. The Super Glue of Ultra-Large Multimers – Characterisation of Recombinant and Platelet Derived von Willebrand Factor [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-super-glue-of-ultra-large-multimers-characterisation-of-recombinant-and-platelet-derived-von-willebrand-factor/. Accessed September 22, 2023.

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