Growth Differentiation Factor-15 Correlates Inversely with Protease-Activated Receptor-1-Mediated Platelet Reactivity in Patients with Left Ventricular Assist Devices.
Maximilian TscharreFranziska WittmannDaniela KitzmantlSilvia LeeBeate EichelbergerPatricia P WadowskiGünther LauferDominik WiedemannSimon PanzerThomas PerkmannDaniel ZimpferThomas GremmelPublished in: Pharmaceuticals (Basel, Switzerland) (2022)
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.
Keyphrases
- left ventricular assist device
- end stage renal disease
- ejection fraction
- left ventricular
- newly diagnosed
- flow cytometry
- low dose
- atrial fibrillation
- type diabetes
- peritoneal dialysis
- heart failure
- gold nanoparticles
- poor prognosis
- sensitive detection
- signaling pathway
- cardiovascular events
- mouse model
- high throughput
- long non coding rna
- aortic stenosis
- coronary artery disease
- quantum dots
- aortic valve
- smoking cessation