Evaluation of von Willebrand factor concentrates by platelet adhesion to collagen using an in vitro flow assay.

ADAMTS13 von Willebrand disease von Willebrand factor

Journal

Research and practice in thrombosis and haemostasis
ISSN: 2475-0379
Titre abrégé: Res Pract Thromb Haemost
Pays: United States
ID NLM: 101703775

Informations de publication

Date de publication:
Jan 2019
Historique:
received: 15 04 2018
accepted: 19 10 2018
entrez: 19 1 2019
pubmed: 19 1 2019
medline: 19 1 2019
Statut: epublish

Résumé

Von Willebrand disease (VWD) results from quantitative or qualitative deficiency of von Willebrand factor (VWF) and is treated using VWF-containing concentrates. Several studies have compared the function of various VWF containing concentrates however this has not been performed using shear based assays. To compare the platelet-capture potential of 10 commercially available, plasma-derived VWF concentrates under shear conditions. VWF containing concentrates were assessed for VWF:Ag, VWF:CB, VWF:RCo, factor VIII:C ADAMTS13 content, VWF multimeric profile and glycan content using lectin binding assays. Free-thiol content of each concentrate was investigated using MPB binding assays. An in vitro flow assay was used to determine the ability of each concentrate to mediate platelet capture to collagen. VWF multimeric analysis revealed reduction of high molecular weight (HMW) forms in four of the concentrates (Alphante, Octanate and Haemoctin, and 8Y). The high MW multimer distribution of the remaining six concentrates (Optivate, Wilate, Fandhi, Wilfactin, Haemate P, and Voncento) was similar to the plasma control. Lectin analysis demonstrated that 8Y had increased amount of T-antigen. Although platelet capture after 5 minutes perfusion was similar for all concentrates; Alphante, Octanate, and Haemoctin, demonstrated the lowest levels of platelet capture after 60 seconds of perfusion. Free-thiol content and ADAMTS13 levels varied widely between the concentrates but was not correlated with function. Alphanate, Octanate, and Haemoctin, lacked HMW multimers and had the lowest initial platelet capture levels suggesting that the presence of VWF HMW multimers are required for initial platelet deposition.

Sections du résumé

BACKGROUND BACKGROUND
Von Willebrand disease (VWD) results from quantitative or qualitative deficiency of von Willebrand factor (VWF) and is treated using VWF-containing concentrates. Several studies have compared the function of various VWF containing concentrates however this has not been performed using shear based assays.
OBJECTIVES OBJECTIVE
To compare the platelet-capture potential of 10 commercially available, plasma-derived VWF concentrates under shear conditions.
METHODS METHODS
VWF containing concentrates were assessed for VWF:Ag, VWF:CB, VWF:RCo, factor VIII:C ADAMTS13 content, VWF multimeric profile and glycan content using lectin binding assays. Free-thiol content of each concentrate was investigated using MPB binding assays. An in vitro flow assay was used to determine the ability of each concentrate to mediate platelet capture to collagen.
RESULTS RESULTS
VWF multimeric analysis revealed reduction of high molecular weight (HMW) forms in four of the concentrates (Alphante, Octanate and Haemoctin, and 8Y). The high MW multimer distribution of the remaining six concentrates (Optivate, Wilate, Fandhi, Wilfactin, Haemate P, and Voncento) was similar to the plasma control. Lectin analysis demonstrated that 8Y had increased amount of T-antigen. Although platelet capture after 5 minutes perfusion was similar for all concentrates; Alphante, Octanate, and Haemoctin, demonstrated the lowest levels of platelet capture after 60 seconds of perfusion. Free-thiol content and ADAMTS13 levels varied widely between the concentrates but was not correlated with function.
CONCLUSION CONCLUSIONS
Alphanate, Octanate, and Haemoctin, lacked HMW multimers and had the lowest initial platelet capture levels suggesting that the presence of VWF HMW multimers are required for initial platelet deposition.

Identifiants

pubmed: 30656286
doi: 10.1002/rth2.12166
pii: S2475-0379(22)01513-8
pmc: PMC6332833
doi:

Types de publication

Journal Article

Langues

eng

Pagination

126-135

Subventions

Organisme : British Heart Foundation
ID : FS/11/3/28632
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/11/50/28984
Pays : United Kingdom

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Auteurs

Anne Riddell (A)

Katharine Dormandy Haemophilia Centre and Thrombosis Unit Royal Free London NHS Foundation Trust London UK.

Saravanan Vinayagam (S)

Katharine Dormandy Haemophilia Centre and Thrombosis Unit Royal Free London NHS Foundation Trust London UK.

Keith Gomez (K)

Katharine Dormandy Haemophilia Centre and Thrombosis Unit Royal Free London NHS Foundation Trust London UK.

Mike Laffan (M)

Department of Haematology Imperial College of Science Technology and Medicine London UK.

Tom McKinnon (T)

Department of Haematology Imperial College of Science Technology and Medicine London UK.

Classifications MeSH