Platelet reactivity influences clot structure as assessed by fractal analysis of viscoelastic properties.
View/ Open
Volume
29
Pagination
162 - 170
DOI
10.1080/09537104.2017.1306039
Journal
Platelets
Issue
Metadata
Show full item recordAbstract
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.
Authors
Knowles, RB; Lawrence, MJ; Ferreira, PM; Hayman, MA; D'Silva, LA; Stanford, SN; Sabra, A; Tucker, AT; Hawkins, KM; Williams, PRCollections
- Centre for Immunobiology [1121]
Language
Licence information
Copyright statements
Related items
Showing items related by title, author, creator and subject.
-
Novel whole blood assay for phenotyping platelet reactivity in mice identifies ICAM-1 as a mediator of platelet-monocyte interaction
Armstrong, PCJ; Kirkby, NS; Chan, MV; Finsterbusch, M; Hogg, N; Nourshargh, S; Warner, TD (2015-09-03) -
Platelet responses to agonists in a cohort of highly characterised platelet donors are consistent over time
Garner, SF; Furnell, A; Kahan, BC; Jones, CI; Attwood, A; Harrison, P; Kelly, AM; Goodall, AH; Cardigan, R; Ouwehand, WH (2017-01) -
Platelet transfusions reduce fibrinolysis but do not restore platelet function during trauma hemorrhage
Vulliamy, P; Gillespie, S; Gall, LS; Green, L; Brohi, K; Davenport, RA (2017-09)