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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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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
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa54403
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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 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.
Keywords: Blood coagulation; Thrombosis; Rheology; Clot microstructure; Fractal dimension
College: Faculty of Medicine, Health and Life Sciences
Funders: UKRI, EP/L024799/1
Start Page: 25
End Page: 30