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. 2022 May;197(4):497-501.
doi: 10.1111/bjh.18145. Epub 2022 Mar 22.

Platelet degranulation and bleeding phenotype in a large cohort of Von Willebrand disease patients

Maurice Swinkels  1 , Ferdows Atiq  1 , Petra E Bürgisser  1 , Iris van Moort  1 , Karina Meijer  2 , Jeroen Eikenboom  3   4 , Karin Fijnvandraat  5 , Karin P M van Galen  6 , Joke de Meris  7 , Saskia E M Schols  8 , Johanna G van der Bom  9 , Marjon H Cnossen  10 , Jan Voorberg  11   12 , Frank W G Leebeek  1 , Ruben Bierings  1 , A J Gerard Jansen  1 ; WiN study group
Collaborators, Affiliations

Platelet degranulation and bleeding phenotype in a large cohort of Von Willebrand disease patients

Maurice Swinkels et al. Br J Haematol. 2022 May.

Abstract

Von Willebrand disease (VWD) is a bleeding disorder caused by quantitative (type 1 or 3) or qualitative (type 2A/2B/2M/2N) defects of circulating von Willebrand factor (VWF). Circulating VWF levels not always fully explain bleeding phenotypes, suggesting a role for alternative factors, like platelets. Here, we investigated platelet factor 4 (PF4) in a large cohort of patients with VWD. PF4 levels were lower in type 2B and current bleeding phenotype was significantly associated with higher PF4 levels, particularly in type 1 VWD. Based on our findings we speculate that platelet degranulation and cargo release may play a role across VWD subtypes.

Keywords: VWD; VWF; bleeding disorders; platelet activation; platelet factor 4.

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Conflict of interest statement

F. W. G. Leebeek received research support from CSL Behring and Shire for performing the Willebrand in the Netherlands (WiN) study, and is consultant for uniQure, Biomarin, Novo Nordisk and Shire, of which the fees go to the institution. F. Atiq received the CSL Behring‐Heimburger Award 2018, and a travel grant from Sobi. I. van Moort received the CSL Behring‐Heimburger Award 2021. A. J. G. Jansen received speaker fees and travel cost payments from 3SBio, Amgen and Novartis, is on the international advisory board at Novartis and received research support from Sanofi, Argenx and CSL Behring. J. Eikenboom received research support from CSL Behring and he has been a teacher on educational activities of Roche. K. P. M. van Galen received unrestricted research support from CSL Behring and Bayer. J. G. van der Bom has received unrestricted research/educational funding for various projects from the following companies: Bayer Schering Pharma, Baxter, CSL Behring, Novo Nordisk, and Pfizer. In addition, she has been a consultant to Baxter and Pfizer, and she has been a teacher on educational activities of Bayer Schering Pharma. M. H. Cnossen has received unrestricted research/educational and travel funding from the following companies: Pfizer, Baxter, Bayer Schering Pharma, CSL Behring, Novo Nordisk and Novartis, and serves as a member on steering boards of Roche and Bayer of which fees go to the institution. K. Fijnvandraat is a member of the European Haemophilia Treatment and Standardization Board sponsored by Baxter, has received unrestricted research grants from CSL Behring and Bayer, and has given lectures at educational symposiums organized by Pfizer, Bayer and Baxter. K. Meijer received speaker fees from Alexion, Bayer and CSL Behring, fees for participation in trial steering committee for Bayer, consulting fees from Uniqure, and fees for participation in data monitoring and endpoint adjudication committee for Octapharma. S. Schols received travel grants from Bayer and Takeda and consultancy grants from Takeda and Novo Nordisk. None of the other authors has a conflict of interest to declare.

Figures

FIGURE 1
FIGURE 1
Platelet factor 4 (PF4) levels in the von Willebrand disease (VWD) cohort. Distribution of PF4 plasma levels in ng/ml are shown per subtype of VWD. Subtypes are type 1 (n = 368), type 2A (n = 125), type 2B (n = 50), type 2M (n = 20), type 2N (n = 12) and type 3 (n = 19). Data shown as median ± interquartile range. ****, p < 0.0001 [Colour figure can be viewed at wileyonlinelibrary.com]
FIGURE 2
FIGURE 2
Platelet factor 4 (PF4) levels in relation to current bleeding phenotype in the von Willebrand disease (VWD) cohort. PF4 plasma levels were related to bleeding that required treatment in the year prior to inclusion. For this analysis, PF4 was subdivided into quartiles: 0.00–65.00 ng/ml (Q1), 65.40–105.90 ng/ml (Q2), 106.30–161.00 ng/ml (Q3) and 161.80–384.50 ng/ml (Q4). The proportion of patients with no bleeding (no bleed, blue) versus bleeding (bleed, red) were plotted across the four quartiles of PF4 levels (A). Bleeding versus PF4 levels are also plotted per subtype and total population (B). Data are shown as proportion (A) and median ± interquartile range (B) [Colour figure can be viewed at wileyonlinelibrary.com]
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