Platelet reactivity influences clot structure as assessed by fractal analysis of viscoelastic properties

Despite the interwoven nature of platelet activation and the coagulation system in thrombosis, few studies relate both analysis of protein and cellular parts of coagulation in the same population. In the present study, we use matched ex vivo samples to determine the influences of standard antiplatel...

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Main Authors: Rebecca B. Knowles, Matthew J. Lawrence, Plinio M. Ferreira, Melissa A. Hayman, Lindsay A. D’Silva, Sophie N. Stanford, Ahmed Sabra, Arthur T. Tucker, Karl M. Hawkins, Phylip R. Williams, Timothy D. Warner, Phillip A. Evans
Format: Article
Language:English
Published: Taylor & Francis Group 2018-02-01
Series:Platelets
Subjects:
Online Access:http://dx.doi.org/10.1080/09537104.2017.1306039
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author Rebecca B. Knowles
Matthew J. Lawrence
Plinio M. Ferreira
Melissa A. Hayman
Lindsay A. D’Silva
Sophie N. Stanford
Ahmed Sabra
Arthur T. Tucker
Karl M. Hawkins
Phylip R. Williams
Timothy D. Warner
Phillip A. Evans
author_facet Rebecca B. Knowles
Matthew J. Lawrence
Plinio M. Ferreira
Melissa A. Hayman
Lindsay A. D’Silva
Sophie N. Stanford
Ahmed Sabra
Arthur T. Tucker
Karl M. Hawkins
Phylip R. Williams
Timothy D. Warner
Phillip A. Evans
author_sort Rebecca B. Knowles
collection DOAJ
description Despite the interwoven nature of platelet activation and the coagulation system in thrombosis, few studies relate both analysis of protein and cellular parts of coagulation in the same population. In the present study, we use matched ex vivo samples to determine the influences of standard antiplatelet therapies on platelet function and use advanced rheological analyses to assess clot formation. Healthy volunteers were recruited following fully informed consent then treated for 7 days with single antiplatelet therapy of aspirin (75 mg) or prasugrel (10 mg) or with dual antiplatelet therapy (DAPT) using aspirin (75 mg) plus prasugrel (10 mg) or aspirin (75 mg) plus ticagrelor (90 mg). Blood samples were taken at day 0 before treatment and at day 7 following treatment. We found that aspirin plus prasugrel or aspirin plus ticagrelor inhibited platelet responses to multiple agonists and reduced P-selectin expression. Significant platelet inhibition was coupled with a reduction in fractal dimension corresponding to reductions in mean relative mass both for aspirin plus prasugrel (−35 ± 16% change, p = 0.04) and for aspirin plus ticagrelor (−45 ± 14% change, p = 0.04). Aspirin alone had no effect upon measures of clot structure, whereas prasugrel reduced fractal dimension and mean relative mass. These data demonstrate that platelets are important determinants of clot structure as assessed by fractal dimension (df) and that effective platelet inhibition is associated with a weaker, more permeable fibrin network. This indicates a strong association between the therapeutic benefits of antiplatelet therapies and their abilities to reduce thrombus density that may be useful in individual patients to determine the functional relationship between platelet reactivity, eventual clot quality, and clinical outcome. df could represent a novel risk stratification biomarker useful in individualizing antiplatelet therapies.
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spelling doaj.art-305d318329e04f2a8626aaf53c2fd6c12023-09-15T10:31:57ZengTaylor & Francis GroupPlatelets0953-71041369-16352018-02-0129216217010.1080/09537104.2017.13060391306039Platelet reactivity influences clot structure as assessed by fractal analysis of viscoelastic propertiesRebecca B. Knowles0Matthew J. Lawrence1Plinio M. Ferreira2Melissa A. Hayman3Lindsay A. D’Silva4Sophie N. Stanford5Ahmed Sabra6Arthur T. Tucker7Karl M. Hawkins8Phylip R. Williams9Timothy D. Warner10Phillip A. Evans11Queen Mary University of LondonMedical School, Swansea UniversityQueen Mary University of LondonQueen Mary University of LondonMedical School, Swansea UniversityMedical School, Swansea UniversityMedical School, Swansea UniversityQueen Mary University of LondonMedical School, Swansea UniversityCollege of Engineering, Swansea UniversityQueen Mary University of LondonMedical School, Swansea UniversityDespite the interwoven nature of platelet activation and the coagulation system in thrombosis, few studies relate both analysis of protein and cellular parts of coagulation in the same population. In the present study, we use matched ex vivo samples to determine the influences of standard antiplatelet therapies on platelet function and use advanced rheological analyses to assess clot formation. Healthy volunteers were recruited following fully informed consent then treated for 7 days with single antiplatelet therapy of aspirin (75 mg) or prasugrel (10 mg) or with dual antiplatelet therapy (DAPT) using aspirin (75 mg) plus prasugrel (10 mg) or aspirin (75 mg) plus ticagrelor (90 mg). Blood samples were taken at day 0 before treatment and at day 7 following treatment. We found that aspirin plus prasugrel or aspirin plus ticagrelor inhibited platelet responses to multiple agonists and reduced P-selectin expression. Significant platelet inhibition was coupled with a reduction in fractal dimension corresponding to reductions in mean relative mass both for aspirin plus prasugrel (−35 ± 16% change, p = 0.04) and for aspirin plus ticagrelor (−45 ± 14% change, p = 0.04). Aspirin alone had no effect upon measures of clot structure, whereas prasugrel reduced fractal dimension and mean relative mass. These data demonstrate that platelets are important determinants of clot structure as assessed by fractal dimension (df) and that effective platelet inhibition is associated with a weaker, more permeable fibrin network. This indicates a strong association between the therapeutic benefits of antiplatelet therapies and their abilities to reduce thrombus density that may be useful in individual patients to determine the functional relationship between platelet reactivity, eventual clot quality, and clinical outcome. df could represent a novel risk stratification biomarker useful in individualizing antiplatelet therapies.http://dx.doi.org/10.1080/09537104.2017.1306039blood coagulationblood plateletsfibrinplatelet aggregation inhibitorsthrombosis
spellingShingle Rebecca B. Knowles
Matthew J. Lawrence
Plinio M. Ferreira
Melissa A. Hayman
Lindsay A. D’Silva
Sophie N. Stanford
Ahmed Sabra
Arthur T. Tucker
Karl M. Hawkins
Phylip R. Williams
Timothy D. Warner
Phillip A. Evans
Platelet reactivity influences clot structure as assessed by fractal analysis of viscoelastic properties
Platelets
blood coagulation
blood platelets
fibrin
platelet aggregation inhibitors
thrombosis
title Platelet reactivity influences clot structure as assessed by fractal analysis of viscoelastic properties
title_full Platelet reactivity influences clot structure as assessed by fractal analysis of viscoelastic properties
title_fullStr Platelet reactivity influences clot structure as assessed by fractal analysis of viscoelastic properties
title_full_unstemmed Platelet reactivity influences clot structure as assessed by fractal analysis of viscoelastic properties
title_short Platelet reactivity influences clot structure as assessed by fractal analysis of viscoelastic properties
title_sort platelet reactivity influences clot structure as assessed by fractal analysis of viscoelastic properties
topic blood coagulation
blood platelets
fibrin
platelet aggregation inhibitors
thrombosis
url http://dx.doi.org/10.1080/09537104.2017.1306039
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