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...
Main Authors: | , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Taylor & Francis Group
2018-02-01
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Series: | Platelets |
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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. |
first_indexed | 2024-03-12T00:27:58Z |
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issn | 0953-7104 1369-1635 |
language | English |
last_indexed | 2024-03-12T00:27:58Z |
publishDate | 2018-02-01 |
publisher | Taylor & Francis Group |
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series | Platelets |
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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