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Growth Differentiation Factor-15 Correlates Inversely with Protease-Activated Receptor-1-Mediated Platelet Reactivity in Patients with Left Ventricular Assist Devices
Growth differentiation factor (GDF)-15 inhibits platelet activation, prevents thrombus formation, and has been linked to bleeding events. This was a prospective study including 51 left-ventricular assist device (LVAD) patients on aspirin and phenprocoumon. Platelet surface expression of activated gl...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031879/ https://www.ncbi.nlm.nih.gov/pubmed/35455481 http://dx.doi.org/10.3390/ph15040484 |
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author | Tscharre, Maximilian Wittmann, Franziska Kitzmantl, Daniela Lee, Silvia Eichelberger, Beate Wadowski, Patricia P. Laufer, Günther Wiedemann, Dominik Panzer, Simon Perkmann, Thomas Zimpfer, Daniel Gremmel, Thomas |
author_facet | Tscharre, Maximilian Wittmann, Franziska Kitzmantl, Daniela Lee, Silvia Eichelberger, Beate Wadowski, Patricia P. Laufer, Günther Wiedemann, Dominik Panzer, Simon Perkmann, Thomas Zimpfer, Daniel Gremmel, Thomas |
author_sort | Tscharre, Maximilian |
collection | PubMed |
description | Growth differentiation factor (GDF)-15 inhibits platelet activation, prevents thrombus formation, and has been linked to bleeding events. This was a prospective study including 51 left-ventricular assist device (LVAD) patients on aspirin and phenprocoumon. Platelet surface expression of activated glycoprotein (GP) IIb/IIIa was assessed by flow cytometry, and platelet aggregation was measured by multiple electrode aggregometry (MEA) in response to arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor-activating peptide (TRAP), a protease-activated-receptor-1 (PAR-1) agonist. GDF-15 was determined with a commercially-available assay. There was a trend towards an inverse correlation of GDF-15 with activated GPIIb/IIIa in response to TRAP (r = −0.275, p = 0.0532) but not in response to AA and ADP. Moreover, GDF-15 correlated with MEA TRAP (r = −0.326, p = 0.0194), whereas it did not correlate with MEA ADP and MEA AA. In a second step, GDF-15 levels in the fourth quartile were defined as high GDF-15. Patients with high GDF-15 showed significantly lower TRAP-inducible platelet aggregation by MEA compared to patients in the first quartile (63 AU vs. 113 AU, p = 0.0065). In conclusion, in LVAD patients receiving state-of-the-art antithrombotic therapy, GDF-15 correlates inversely with residual platelet reactivity via PAR-1. |
format | Online Article Text |
id | pubmed-9031879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90318792022-04-23 Growth Differentiation Factor-15 Correlates Inversely with Protease-Activated Receptor-1-Mediated Platelet Reactivity in Patients with Left Ventricular Assist Devices Tscharre, Maximilian Wittmann, Franziska Kitzmantl, Daniela Lee, Silvia Eichelberger, Beate Wadowski, Patricia P. Laufer, Günther Wiedemann, Dominik Panzer, Simon Perkmann, Thomas Zimpfer, Daniel Gremmel, Thomas Pharmaceuticals (Basel) Article Growth differentiation factor (GDF)-15 inhibits platelet activation, prevents thrombus formation, and has been linked to bleeding events. This was a prospective study including 51 left-ventricular assist device (LVAD) patients on aspirin and phenprocoumon. Platelet surface expression of activated glycoprotein (GP) IIb/IIIa was assessed by flow cytometry, and platelet aggregation was measured by multiple electrode aggregometry (MEA) in response to arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor-activating peptide (TRAP), a protease-activated-receptor-1 (PAR-1) agonist. GDF-15 was determined with a commercially-available assay. There was a trend towards an inverse correlation of GDF-15 with activated GPIIb/IIIa in response to TRAP (r = −0.275, p = 0.0532) but not in response to AA and ADP. Moreover, GDF-15 correlated with MEA TRAP (r = −0.326, p = 0.0194), whereas it did not correlate with MEA ADP and MEA AA. In a second step, GDF-15 levels in the fourth quartile were defined as high GDF-15. Patients with high GDF-15 showed significantly lower TRAP-inducible platelet aggregation by MEA compared to patients in the first quartile (63 AU vs. 113 AU, p = 0.0065). In conclusion, in LVAD patients receiving state-of-the-art antithrombotic therapy, GDF-15 correlates inversely with residual platelet reactivity via PAR-1. MDPI 2022-04-15 /pmc/articles/PMC9031879/ /pubmed/35455481 http://dx.doi.org/10.3390/ph15040484 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tscharre, Maximilian Wittmann, Franziska Kitzmantl, Daniela Lee, Silvia Eichelberger, Beate Wadowski, Patricia P. Laufer, Günther Wiedemann, Dominik Panzer, Simon Perkmann, Thomas Zimpfer, Daniel Gremmel, Thomas Growth Differentiation Factor-15 Correlates Inversely with Protease-Activated Receptor-1-Mediated Platelet Reactivity in Patients with Left Ventricular Assist Devices |
title | Growth Differentiation Factor-15 Correlates Inversely with Protease-Activated Receptor-1-Mediated Platelet Reactivity in Patients with Left Ventricular Assist Devices |
title_full | Growth Differentiation Factor-15 Correlates Inversely with Protease-Activated Receptor-1-Mediated Platelet Reactivity in Patients with Left Ventricular Assist Devices |
title_fullStr | Growth Differentiation Factor-15 Correlates Inversely with Protease-Activated Receptor-1-Mediated Platelet Reactivity in Patients with Left Ventricular Assist Devices |
title_full_unstemmed | Growth Differentiation Factor-15 Correlates Inversely with Protease-Activated Receptor-1-Mediated Platelet Reactivity in Patients with Left Ventricular Assist Devices |
title_short | Growth Differentiation Factor-15 Correlates Inversely with Protease-Activated Receptor-1-Mediated Platelet Reactivity in Patients with Left Ventricular Assist Devices |
title_sort | growth differentiation factor-15 correlates inversely with protease-activated receptor-1-mediated platelet reactivity in patients with left ventricular assist devices |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031879/ https://www.ncbi.nlm.nih.gov/pubmed/35455481 http://dx.doi.org/10.3390/ph15040484 |
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