Evaluation of von Willebrand factor concentrates by platelet adhesion to collagen using an in vitro flow assay
Author(s)
Riddell, Anne
Vinayagam, Saravanan
Gomez, Keith
Laffan, Mike
McKinnon, Tom
Type
Journal Article
Abstract
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
To compare the platelet‐capture potential of 10 commercially available, plasma‐derived VWF concentrates under shear conditions.
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
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
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.
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
To compare the platelet‐capture potential of 10 commercially available, plasma‐derived VWF concentrates under shear conditions.
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
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
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.
Date Issued
2019-01-01
Date Acceptance
2018-10-19
Citation
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS, 2019, 3 (1), pp.126-135
ISSN
2475-0379
Publisher
WILEY
Start Page
126
End Page
135
Journal / Book Title
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
Volume
3
Issue
1
Copyright Statement
© 2018 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals, Inc on behalf of International Society on Thrombosis
and Haemostasis. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in
any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
and Haemostasis. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in
any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Sponsor
British Heart Foundation
British Heart Foundation
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000455653800019&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
FS/11/3/28632
PG/11/50/28984
Subjects
Science & Technology
Life Sciences & Biomedicine
Hematology
ADAMTS13
von Willebrand factor
von Willebrand disease
FACTOR-VIII
VONWILLEBRAND-FACTOR
HIGH-PURITY
ADAMTS13 CONTENT
GLYCOPROTEIN IB
DISEASE VWD
PLASMA
ANTIGEN
SUBENDOTHELIUM
GLYCOSYLATION
Publication Status
Published
Date Publish Online
2018-12-07