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

WiN study group

doi:https://doi.org/10.1111/bjh.18145

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

WiN study group

Research output: Contribution to journal › Article › Academic › peer-review

2 Citations (Scopus)

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.

Original language	English
Pages (from-to)	497-501
Number of pages	5
Journal	British journal of haematology
Volume	197
Issue number	4
DOIs	https://doi.org/10.1111/bjh.18145
Publication status	Published - 1 May 2022

Keywords

VWD
VWF
bleeding disorders
platelet activation
platelet factor 4

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https://doi.org/10.1111/bjh.18145

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@article{84e739bf0f7348c7b327ee012a9977d5,

title = "Platelet degranulation and bleeding phenotype in a large cohort of Von Willebrand disease patients",

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",

author = "Maurice Swinkels and Ferdows Atiq and B{\"u}rgisser, {Petra E.} and {van Moort}, Iris and Karina Meijer and Jeroen Eikenboom and Karin Fijnvandraat and {van Galen}, {Karin P. M.} and {de Meris}, Joke and Schols, {Saskia E. M.} and {van der Bom}, {Johanna G.} and Cnossen, {Marjon H.} and Jan Voorberg and Leebeek, {Frank W. G.} and Ruben Bierings and Jansen, {A. J. Gerard} and {WiN study group} and K. Fijnvandraat and M. Coppens and {de Meris}, J. and L. Nieuwenhuizen and K. Meijer and Tamminga, {R. Y. J.} and Ypma, {P. F.} and Eikenboom, {H. C. J.} and {van der Bom}, {J. G.} and Smiers, {F. J. W.} and B. Granzen and F. Moenen and P. Brons and Schols, {S. E. M.} and Leebeek, {F. W. G.} and Cnossen, {M. H.} and F. Atiq and {van Kwawegen}, {C. B.} and {van Galen}, {K. P. M.}",

note = "Funding Information: 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. Funding Information: This work was supported by grants from the Landsteiner Stichting voor Bloedtransfusie Research (LSBR-1707) (Ruben Bierings), the Netherlands Organization for Scientific Research (NWO NWA.1160.18.038) (Ruben Bierings and Iris van Moort) and an EHA Clinical Research Fellowship (A. J. Gerard Jansen). The WiN study was supported (in part) by research funding from the Dutch Haemophilia Foundation (Stichting Haemophilia) (Frank W. G. Leebeek) and CSL Behring (Frank W. G. Leebeek, unrestricted grant). Funding Information: This work was supported by grants from the Landsteiner Stichting voor Bloedtransfusie Research (LSBR‐1707) (Ruben Bierings), the Netherlands Organization for Scientific Research (NWO NWA.1160.18.038) (Ruben Bierings and Iris van Moort) and an EHA Clinical Research Fellowship (A. J. Gerard Jansen). The WiN study was supported (in part) by research funding from the Dutch Haemophilia Foundation (Stichting Haemophilia) (Frank W. G. Leebeek) and CSL Behring (Frank W. G. Leebeek, unrestricted grant). Publisher Copyright: {\textcopyright} 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.",

year = "2022",

month = may,

day = "1",

doi = "https://doi.org/10.1111/bjh.18145",

language = "English",

volume = "197",

pages = "497--501",

journal = "British journal of haematology",

issn = "0007-1048",

publisher = "Wiley-Blackwell",

number = "4",

}

TY - JOUR

T1 - Platelet degranulation and bleeding phenotype in a large cohort of Von Willebrand disease patients

AU - Swinkels, Maurice

AU - Atiq, Ferdows

AU - Bürgisser, Petra E.

AU - van Moort, Iris

AU - Meijer, Karina

AU - Eikenboom, Jeroen

AU - Fijnvandraat, Karin

AU - van Galen, Karin P. M.

AU - de Meris, Joke

AU - Schols, Saskia E. M.

AU - van der Bom, Johanna G.

AU - Cnossen, Marjon H.

AU - Voorberg, Jan

AU - Leebeek, Frank W. G.

AU - Bierings, Ruben

AU - Jansen, A. J. Gerard

AU - WiN study group

AU - Fijnvandraat, K.

AU - Coppens, M.

AU - de Meris, J.

AU - Nieuwenhuizen, L.

AU - Meijer, K.

AU - Tamminga, R. Y. J.

AU - Ypma, P. F.

AU - Eikenboom, H. C. J.

AU - van der Bom, J. G.

AU - Smiers, F. J. W.

AU - Granzen, B.

AU - Moenen, F.

AU - Brons, P.

AU - Schols, S. E. M.

AU - Leebeek, F. W. G.

AU - Cnossen, M. H.

AU - Atiq, F.

AU - van Kwawegen, C. B.

AU - van Galen, K. P. M.

N1 - Funding Information: 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. Funding Information: This work was supported by grants from the Landsteiner Stichting voor Bloedtransfusie Research (LSBR-1707) (Ruben Bierings), the Netherlands Organization for Scientific Research (NWO NWA.1160.18.038) (Ruben Bierings and Iris van Moort) and an EHA Clinical Research Fellowship (A. J. Gerard Jansen). The WiN study was supported (in part) by research funding from the Dutch Haemophilia Foundation (Stichting Haemophilia) (Frank W. G. Leebeek) and CSL Behring (Frank W. G. Leebeek, unrestricted grant). Funding Information: This work was supported by grants from the Landsteiner Stichting voor Bloedtransfusie Research (LSBR‐1707) (Ruben Bierings), the Netherlands Organization for Scientific Research (NWO NWA.1160.18.038) (Ruben Bierings and Iris van Moort) and an EHA Clinical Research Fellowship (A. J. Gerard Jansen). The WiN study was supported (in part) by research funding from the Dutch Haemophilia Foundation (Stichting Haemophilia) (Frank W. G. Leebeek) and CSL Behring (Frank W. G. Leebeek, unrestricted grant). Publisher Copyright: © 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

PY - 2022/5/1

Y1 - 2022/5/1

N2 - 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.

AB - 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.

KW - VWD

KW - VWF

KW - bleeding disorders

KW - platelet activation

KW - platelet factor 4

UR - http://www.scopus.com/inward/record.url?scp=85133798606&partnerID=8YFLogxK

U2 - https://doi.org/10.1111/bjh.18145

DO - https://doi.org/10.1111/bjh.18145

M3 - Article

C2 - 36165954

SN - 0007-1048

VL - 197

SP - 497

EP - 501

JO - British journal of haematology

JF - British journal of haematology

IS - 4

ER -

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

Abstract

Keywords

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