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. 2023 Feb 17;12(4):1627.
doi: 10.3390/jcm12041627.

Growth Differentiation Factor 15 Is Associated with Platelet Reactivity in Patients with Acute Coronary Syndrome

David Mutschlechner  1 , Maximilian Tscharre  2   3 , Patricia P Wadowski  3 , Joseph Pultar  3   4 , Constantin Weikert  3 , Silvia Lee  3 , Beate Eichelberger  5 , Simon Panzer  5 , Thomas Perkmann  6 , Thomas Gremmel  1   3   7
Affiliations

Growth Differentiation Factor 15 Is Associated with Platelet Reactivity in Patients with Acute Coronary Syndrome

David Mutschlechner et al. J Clin Med. .

Abstract

Bleeding events in patients with acute coronary syndrome (ACS) are a risk factor for adverse outcomes, including mortality. We investigated the association of growth differentiation factor (GDF)-15, an established predictor of bleeding complications, with on-treatment platelet reactivity in ACS patients undergoing coronary stenting receiving prasugrel or ticagrelor. Platelet aggregation was measured by multiple electrode aggregometry (MEA) in response to adenosine diphosphate (ADP), arachidonic acid (AA), thrombin receptor-activating peptide (TRAP, a protease-activated receptor-1 (PAR-1) agonist), AYPGKF (a PAR-4 agonist) and collagen (COL). GDF-15 levels were measured using a commercially available assay. GDF-15 correlated inversely with MEA ADP (r = -0.202, p = 0.004), MEA AA (r = -0.139, p = 0.048) and MEA TRAP (r = -0.190, p = 0.007). After adjustment, GDF-15 was significantly associated with MEA TRAP (β = -0.150, p = 0.044), whereas no significant associations were detectable for the other agonists. Patients with low platelet reactivity in response to ADP had significantly higher GDF-15 levels (p = 0.005). In conclusion, GDF-15 is inversely associated with TRAP-inducible platelet aggregation in ACS patients treated with state-of-the-art antiplatelet therapy and significantly elevated in patients with low platelet reactivity in response to ADP.

Keywords: acute coronary syndrome; growth differentiation factor 15; platelet reactivity; prasugrel; ticagrelor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Correlations of GDF-15 with platelet aggregation by multiple electrode aggregometry (MEA). (a) Scatter plot showing GDF-15 (x-axis) versus adenosine diphosphate (ADP)-inducible platelet aggregation by MEA (y-axis). (b) Scatter plot showing GDF-15 (x-axis) versus arachidonic acid (AA)-inducible platelet aggregation by MEA (y-axis). (c) Scatter plot showing GDF-15 (x-axis) versus thrombin receptor-activating peptide (TRAP)-inducible platelet aggregation by MEA (y-axis). (d) Scatter plot showing GDF-15 (x-axis) versus collagen (COL)-inducible platelet aggregation by MEA (y-axis). (e) Scatter plot showing GDF-15 (x-axis) versus AYPGKF-inducible platelet aggregation by MEA (y-axis).
Figure 2
Figure 2
GDF-15 levels in patients with normal or high platelet reactivity versus low platelet reactivity to adenosine diphosphate (ADP). The boundaries of the box show the lower and upper quartiles, the line inside the box represents the median. Whiskers were drawn from the edge of the box to the highest and lowest values that are outside the box but within 1.5 times the box length.
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    Mutschlechner D, Tscharre M, Wadowski PP, Lee S, Pultar J, Weikert C, Panzer S, Gremmel T. Mutschlechner D, et al. Res Pract Thromb Haemost. 2025 Feb 20;9(2):102704. doi: 10.1016/j.rpth.2025.102704. eCollection 2025 Feb. Res Pract Thromb Haemost. 2025. PMID: 40177222 Free PMC article.

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