Proteomics in thrombosis research

Abstract

A State of the Art lecture titled “Proteomics in Thrombosis Research” was presented at the ISTH Congress in 2021. In clinical practice, there is a need for improved plasma biomarker‐based tools for diagnosis and risk prediction of venous thromboembolism (VTE). Analysis of blood, to identify plasma proteins with potential utility for such tools, could enable an individualized approach to treatment and prevention. Technological advances to study the plasma proteome on a large scale allows broad screening for the identification of novel plasma biomarkers, both by targeted and nontargeted proteomics methods. However, assay limitations need to be considered when interpreting results, with orthogonal validation required before conclusions are drawn. Here, we review and provide perspectives on the application of affinity‐ and mass spectrometry‐based methods for the identification and analysis of plasma protein biomarkers, with potential application in the field of VTE. We also provide a future perspective on discovery strategies and emerging technologies for targeted proteomics in thrombosis research. Finally, we summarize relevant new data on this topic, presented during the 2021 ISTH Congress.

Identifying novel biomarkers using proteomics to predict cancer-associated thrombosis

“…29 Targeted approaches demonstrate high sensitivity, specificity, and reproducibility, proving effective for protein identification in diverse samples, and excluding the need for affinity reagents. [30][31][32] MS proteomics offers some advantages in comparison to conventional affinity-based assays (Table 1), such as its high specificity and ability to process large sample volumes. In addition, MS allows for the examination of post-translational modifications and characterization of isoforms, enhancing its versatility in protein analysis.…”

“…35 This disparity contributes to the weak correlation observed between MS and affinity-based platforms. 30…”

Innovative applications of global assays of hemostasis

“…Though facing several technical limitations, the profiling of a large number of proteins could lead to the discovery of novel (combined) biomarkers in hemostatic pathologies. 137 With respect to global assays of hemostasis, proteomics may allow further exploration of plasma proteins as determinants of assay parameters. This could help guide the work-up of confirmatory laboratory assays following abnormal results.…”