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Abnormal clot microstructure formed in blood containing HIT-like antibodies

Bethan Thomas, Rebecca J. Hambly, John W. Weisel, Lubica Rauova, Nafiseh Badiei, Rowan Brown Orcid Logo, Cathy Thornton Orcid Logo, Rhodri Williams Orcid Logo, Karl Hawkins Orcid Logo

Thrombosis Research, Volume: 193, Pages: 25 - 30

Swansea University Authors: Bethan Thomas, Nafiseh Badiei, Rowan Brown Orcid Logo, Cathy Thornton Orcid Logo, Rhodri Williams Orcid Logo, Karl Hawkins Orcid Logo

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DOI (Published version): 10.1016/j.thromres.2020.05.029

Abstract

IntroductionThrombosis is a severe and frequent complication of heparin-induced thrombocytopenia (HIT). However, there is currently no knowledge of the effects of HIT-like antibodies on the resulting microstructure of the formed clot, despite such information being linked to thrombotic events. We ev...

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Published in: Thrombosis Research
ISSN: 0049-3848
Published: Elsevier BV 2020
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URI: https://cronfa.swan.ac.uk/Record/cronfa54403
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However, there is currently no knowledge of the effects of HIT-like antibodies on the resulting microstructure of the formed clot, despite such information being linked to thrombotic events. We evaluate the effect of the addition of pathogenic HIT-like antibodies to blood on the resulting microstructure of the formed clot.Materials and methodsPathogenic HIT-like antibodies (KKO) and control antibodies (RTO) were added to samples of whole blood containing Unfractionated Heparin and Platelet Factor 4. The formed clot microstructure was investigated by rheological measurements (fractal dimension; df) and scanning electron microscopy (SEM), and platelet activation was measured by flow cytometry.Results and conclusionsOur results revealed striking effects of KKO on clot microstructure. A significant difference in df was found between samples containing KKO (df = 1.80) versus RTO (df = 1.74; p &lt; 0.0001). This increase in df was often associated with an increase in activated platelets. SEM images of the clots formed with KKO showed a network consisting of a highly branched and compact arrangement of thin fibrin fibres, typically found in thrombotic disease. This is the first study to identify significant changes in clot microstructure formed in blood containing HIT-like antibodies. These observed alterations in clot microstructure can be potentially exploited as a much-needed biomarker for the detection, management and monitoring of HIT-associated thrombosis.</abstract><type>Journal Article</type><journal>Thrombosis Research</journal><volume>193</volume><journalNumber/><paginationStart>25</paginationStart><paginationEnd>30</paginationEnd><publisher>Elsevier BV</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0049-3848</issnPrint><issnElectronic/><keywords>Blood coagulation; Thrombosis; Rheology; Clot microstructure; Fractal dimension</keywords><publishedDay>1</publishedDay><publishedMonth>9</publishedMonth><publishedYear>2020</publishedYear><publishedDate>2020-09-01</publishedDate><doi>10.1016/j.thromres.2020.05.029</doi><url/><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm/><funders>UKRI, EP/L024799/1</funders><projectreference/><lastEdited>2022-12-06T15:08:16.3997773</lastEdited><Created>2020-06-08T12:07:47.6290943</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>Bethan</firstname><surname>Thomas</surname><order>1</order></author><author><firstname>Rebecca J.</firstname><surname>Hambly</surname><order>2</order></author><author><firstname>John W.</firstname><surname>Weisel</surname><order>3</order></author><author><firstname>Lubica</firstname><surname>Rauova</surname><order>4</order></author><author><firstname>Nafiseh</firstname><surname>Badiei</surname><order>5</order></author><author><firstname>Rowan</firstname><surname>Brown</surname><orcid>0000-0003-3628-2524</orcid><order>6</order></author><author><firstname>Cathy</firstname><surname>Thornton</surname><orcid>0000-0002-5153-573X</orcid><order>7</order></author><author><firstname>Rhodri</firstname><surname>Williams</surname><orcid>0000-0002-6912-5288</orcid><order>8</order></author><author><firstname>Karl</firstname><surname>Hawkins</surname><orcid>0000-0003-0174-4151</orcid><order>9</order></author></authors><documents><document><filename>54403__17441__237f42a109f943cab031d3a2f4432e22.pdf</filename><originalFilename>54403VOR.pdf</originalFilename><uploaded>2020-06-08T12:10:48.6294129</uploaded><type>Output</type><contentLength>1319274</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>Released under the terms of a Creative Commons Attribution License (CC-BY).</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language><licence>http://creativecommons.org/licenses/by/4.0/</licence></document></documents><OutputDurs/></rfc1807>
spelling 2022-12-06T15:08:16.3997773 v2 54403 2020-06-08 Abnormal clot microstructure formed in blood containing HIT-like antibodies 09ea6b20932c7cf460b9e3459130be1f Bethan Thomas Bethan Thomas true false c82cd1b82759801ab0045cb9f0047b06 Nafiseh Badiei Nafiseh Badiei true false d7db8d42c476dfa69c15ce06d29bd863 0000-0003-3628-2524 Rowan Brown Rowan Brown true false c71a7a4be7361094d046d312202bce0c 0000-0002-5153-573X Cathy Thornton Cathy Thornton true false 642bf793695f412ed932f1ea4d9bc3f1 0000-0002-6912-5288 Rhodri Williams Rhodri Williams true false 77c39404a9a98c6e2283d84815cba053 0000-0003-0174-4151 Karl Hawkins Karl Hawkins true false 2020-06-08 MEDS IntroductionThrombosis is a severe and frequent complication of heparin-induced thrombocytopenia (HIT). However, there is currently no knowledge of the effects of HIT-like antibodies on the resulting microstructure of the formed clot, despite such information being linked to thrombotic events. We evaluate the effect of the addition of pathogenic HIT-like antibodies to blood on the resulting microstructure of the formed clot.Materials and methodsPathogenic HIT-like antibodies (KKO) and control antibodies (RTO) were added to samples of whole blood containing Unfractionated Heparin and Platelet Factor 4. The formed clot microstructure was investigated by rheological measurements (fractal dimension; df) and scanning electron microscopy (SEM), and platelet activation was measured by flow cytometry.Results and conclusionsOur results revealed striking effects of KKO on clot microstructure. A significant difference in df was found between samples containing KKO (df = 1.80) versus RTO (df = 1.74; p < 0.0001). This increase in df was often associated with an increase in activated platelets. SEM images of the clots formed with KKO showed a network consisting of a highly branched and compact arrangement of thin fibrin fibres, typically found in thrombotic disease. This is the first study to identify significant changes in clot microstructure formed in blood containing HIT-like antibodies. These observed alterations in clot microstructure can be potentially exploited as a much-needed biomarker for the detection, management and monitoring of HIT-associated thrombosis. Journal Article Thrombosis Research 193 25 30 Elsevier BV 0049-3848 Blood coagulation; Thrombosis; Rheology; Clot microstructure; Fractal dimension 1 9 2020 2020-09-01 10.1016/j.thromres.2020.05.029 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University UKRI, EP/L024799/1 2022-12-06T15:08:16.3997773 2020-06-08T12:07:47.6290943 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Bethan Thomas 1 Rebecca J. Hambly 2 John W. Weisel 3 Lubica Rauova 4 Nafiseh Badiei 5 Rowan Brown 0000-0003-3628-2524 6 Cathy Thornton 0000-0002-5153-573X 7 Rhodri Williams 0000-0002-6912-5288 8 Karl Hawkins 0000-0003-0174-4151 9 54403__17441__237f42a109f943cab031d3a2f4432e22.pdf 54403VOR.pdf 2020-06-08T12:10:48.6294129 Output 1319274 application/pdf Version of Record true Released under the terms of a Creative Commons Attribution License (CC-BY). true eng http://creativecommons.org/licenses/by/4.0/
title Abnormal clot microstructure formed in blood containing HIT-like antibodies
spellingShingle Abnormal clot microstructure formed in blood containing HIT-like antibodies
Bethan Thomas
Nafiseh Badiei
Rowan Brown
Cathy Thornton
Rhodri Williams
Karl Hawkins
title_short Abnormal clot microstructure formed in blood containing HIT-like antibodies
title_full Abnormal clot microstructure formed in blood containing HIT-like antibodies
title_fullStr Abnormal clot microstructure formed in blood containing HIT-like antibodies
title_full_unstemmed Abnormal clot microstructure formed in blood containing HIT-like antibodies
title_sort Abnormal clot microstructure formed in blood containing HIT-like antibodies
author_id_str_mv 09ea6b20932c7cf460b9e3459130be1f
c82cd1b82759801ab0045cb9f0047b06
d7db8d42c476dfa69c15ce06d29bd863
c71a7a4be7361094d046d312202bce0c
642bf793695f412ed932f1ea4d9bc3f1
77c39404a9a98c6e2283d84815cba053
author_id_fullname_str_mv 09ea6b20932c7cf460b9e3459130be1f_***_Bethan Thomas
c82cd1b82759801ab0045cb9f0047b06_***_Nafiseh Badiei
d7db8d42c476dfa69c15ce06d29bd863_***_Rowan Brown
c71a7a4be7361094d046d312202bce0c_***_Cathy Thornton
642bf793695f412ed932f1ea4d9bc3f1_***_Rhodri Williams
77c39404a9a98c6e2283d84815cba053_***_Karl Hawkins
author Bethan Thomas
Nafiseh Badiei
Rowan Brown
Cathy Thornton
Rhodri Williams
Karl Hawkins
author2 Bethan Thomas
Rebecca J. Hambly
John W. Weisel
Lubica Rauova
Nafiseh Badiei
Rowan Brown
Cathy Thornton
Rhodri Williams
Karl Hawkins
format Journal article
container_title Thrombosis Research
container_volume 193
container_start_page 25
publishDate 2020
institution Swansea University
issn 0049-3848
doi_str_mv 10.1016/j.thromres.2020.05.029
publisher Elsevier BV
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description IntroductionThrombosis is a severe and frequent complication of heparin-induced thrombocytopenia (HIT). However, there is currently no knowledge of the effects of HIT-like antibodies on the resulting microstructure of the formed clot, despite such information being linked to thrombotic events. We evaluate the effect of the addition of pathogenic HIT-like antibodies to blood on the resulting microstructure of the formed clot.Materials and methodsPathogenic HIT-like antibodies (KKO) and control antibodies (RTO) were added to samples of whole blood containing Unfractionated Heparin and Platelet Factor 4. The formed clot microstructure was investigated by rheological measurements (fractal dimension; df) and scanning electron microscopy (SEM), and platelet activation was measured by flow cytometry.Results and conclusionsOur results revealed striking effects of KKO on clot microstructure. A significant difference in df was found between samples containing KKO (df = 1.80) versus RTO (df = 1.74; p < 0.0001). This increase in df was often associated with an increase in activated platelets. SEM images of the clots formed with KKO showed a network consisting of a highly branched and compact arrangement of thin fibrin fibres, typically found in thrombotic disease. This is the first study to identify significant changes in clot microstructure formed in blood containing HIT-like antibodies. These observed alterations in clot microstructure can be potentially exploited as a much-needed biomarker for the detection, management and monitoring of HIT-associated thrombosis.
published_date 2020-09-01T12:04:17Z
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