Abstract Number: VPB0372
Meeting: ISTH 2022 Congress
Background: Recent evidence suggests that the two subtypes of pulmonary embolism (PE), isolated PE (iPE) and deep vein thrombosis (DVT)-associated PE (DVT-PE) differ in terms of plasma protein profiles in the acute phase.
Aims: This study aimed to determine specific plasma signatures for proteins related to platelets in acute iPE and DVT-PE compared to isolated DVT (iDVT).
Methods: Within the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism (GMP-VTE) Project, a multicenter prospective cohort study of 693 confirmed VTE cases, a highly sensitive targeted proteomics approach based on dual-antibody proximity extension assay was applied. Whole leg ultrasonography was performed to exclude DVT in individuals with iPE. This study was approved by the local Ethics committee including signed patient informed consent. A total of 135 platelet-related candidate proteins were selected from 444 proteins according to mass spectrometry-based platelet proteomics databases and a systematic literature screen. LASSO-regularized logistic regression models were utilized for analysis of regulated proteins.
Results: LASSO-analysis selected 33 and 30 of 135 platelet-related proteins in iPE and DVT-PE vs. iDVT, respectively. The majority of the selected proteins did not overlap between PE-subtypes. While iPE-specific proteins were assigned to be predominantly released via shedding mechanisms and extracellular vesicles, degranulation was identified as a major release mechanism assigned to DVT-associated PE-specific proteins. Network analysis demonstrated three interconnected clusters of specifically regulated proteins in iPE linked to immunoreceptor signaling, pathogen clearance and chemotaxis, whereas for DVT-associated PE one cluster was linked to tissue remodeling and leukocyte trafficking.
Conclusion(s): Machine learning-based analysis revealed specific plasma signatures and differential release mechanisms of proteins related to platelets in iPE and DVT- PE. These data suggest that the platelet protein releasate contributes to the differential regulation of plasma proteins in acute PE compared to iDVT, which may be associated with different platelet activation patterns.
GB is supported by EU-TICARDIO No. 813409.
To cite this abstract in AMA style:Baidildinova G, ten Cate V, Nagler M, Panova-Noeva M, Rapp S, Koeck T, Prochaska J, Heitmeier S, Gerdes C, Schwers S, Konstantinides S, Münzel T, Espinola-Klein C, Lackner K, Spronk H, ten Cate H, van der meijden P, Leineweber K, Wild P, Jurk K. Subtype-specific plasma signatures of platelet-related protein releasate in acute pulmonary embolism [abstract]. https://abstracts.isth.org/abstract/subtype-specific-plasma-signatures-of-platelet-related-protein-releasate-in-acute-pulmonary-embolism/. Accessed March 4, 2024.
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