Metabolomics profiling in venous thromboembolism and its chronic sequelae - A systematic review

High-throughput metabolomics studies have advanced the identification of novel biomarkers and enhanced the understanding of the pathogenesis of venous thrombosis. This systematic review aims to summarize metabolomics research conducted on venous thromboembolism (VTE), as well as its chronic sequelae, including chronic thromboembolic pulmonary hypertension (CTEPH) and post-thrombotic syndrome (PTS), encompassing both pre-clinical and clinical investigations.

A systematic search using relevant keywords related to metabolomics profiling and venous thromboembolism was conducted across four databases (PubMed, Embase, Scopus, and Web of Science). Quality assessment for animal studies was performed using SYRCLE, and for human studies, QUADOMICS was used. The study protocol is registered in PROSPERO under registry code CRD42024529490.

Multiple metabolic disturbances were identified in various venous thrombotic conditions, including dysregulations in cellular respiration and the metabolism of carbohydrates, amino acids, lipids, and nucleic acids. Notably, altered levels of serum amino acids and their derivatives were frequently reported in patients with venous thrombosis, though findings regarding specific amino acids such as alanine, arginine, and tryptophan were inconsistent. Additionally, disruptions in tricarboxylic acid (TCA) cycle metabolites were commonly observed. Pathway enrichment analysis revealed significant involvement of several metabolic pathways, including valine, leucine, and isoleucine biosynthesis; alanine and aspartate metabolism; d-glutamine and D-glutamate metabolism; and arginine metabolism.

This systematic review offers a comprehensive overview of metabolomics research in venous thromboembolism and its chronic sequelae, identifying the most affected metabolic pathways associated with disease progression.