Abstract Number: PB1716
Meeting: ISTH 2020 Congress
Background: Upon activation, platelets release soluble and vesicular signals, termed the platelet releasate (PR), which plays critical role in haemostasis, wound healing and inflammatory responses. We have previously shown the stability of the PR proteome across healthy populations and reported fundamental PR changes in high-stress physiologic conditions, including pregnancy. We hypothesised that the PR could contribute novel biomarkers in early-onset preeclampsia (EOP), a potentially dangerous pregnancy-associated condition in which clinical prediction tools are urgently required to aid decision-making when facing challenging competing maternal and fetal risks.
1. To characterise PR changes in EOP.
2. Identify candidate biomarker proteins through data-dependent mass spectrometry analysis (DDA).
3. Assess and confirm these differences through a data-independent mass spectrometry (DIA) approach.
Methods: Thrombin-induced PRs from 22 EOP patients (onset < 34 gestational weeks) and matched healthy controls, were obtained with informed consent. After trypsin/lys-C double digest, samples were subjected to DDA and DIA analysis. Bioinformatic and statistical analysis was carried out using Perseus, Skyline, mapDIA and RStudio.
Results: Utilising a DDA approach we quantified >700 PR proteins and discovered that 69 and 14 proteins (including condition-specific proteins) were abnormally released in pregnancy and EOP patients respectively, compared to controls. Moreover 8/14 differential EOP proteins could be used to identify patients at high-risk of developing severe EOP with 90% accuracy. Subsequently, samples were subjected to DIA analysis and peptides from identified candidate biomarker-proteins (69+14) were further assessed. 59 peptides were confirmed to be abnormally released in EOP. Random forest analysis revealed that the combination of 6 of these peptides can diagnose EOP with 100% accuracy. Furthermore, a combination of 11/59 peptides improved our stratification of high-risk EOP patients (100% accuracy).
Conclusions: The PR proteome is dynamic and changes significantly in pathologic conditions such as EOP. The PR is a potential source of novel diagnostic and clinically-predictive biomarkers in EOP.
To cite this abstract in AMA style:Szklanna PB, Parsons MEM, Wynne K, O'Connor H, Higgins M, Egan K, Ni Ainle F, Maguire PB. In-Depth Platelet Releasate Proteome Profiling: A Novel Source of Biomarkers for Early-Onset Preeclampsia [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/in-depth-platelet-releasate-proteome-profiling-a-novel-source-of-biomarkers-for-early-onset-preeclampsia/. Accessed January 27, 2022.
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