Exploration of the plasma proteomic profile of patients at risk of thromboembolic events

Abstract

Background

The elevated health burden of thromboembolic events necessitates development of blood-based risk monitoring tools.

Objectives

We explored the potential of mass spectrometry–based plasma proteomics to provide insights into underlying plasma protein signatures associated with treatment and occurrence of thromboembolic events.

Methods

Utilizing a high-throughput, data-independent acquisition, discovery-based proteomics workflow, we analyzed 434 plasma proteomes from different groups of individuals with elevated risk of thromboembolic events, including individuals I) on vitamin K antagonists (VKAs; n = 130), II) with a prior venous thromboembolism (n = 10), III) with acute cerebral venous sinus thrombosis (n = 10, and IV) with SARS-CoV-2 infection (n = 67). Plasma protein levels measured with mass spectrometry were correlated with international normalized ratio and conventional clinical laboratory measurements. Plasma profile differences between different groups were assessed using principal component analysis, moderated t-test, and clustering analysis.

Results

Plasma protein levels were in agreement with conventional clinical laboratory parameters, including albumin and fibrinogen. Levels of vitamin K–dependent proteins inversely correlated with international normalized ratio. In the individual studies, we found decreased levels of vitamin K–dependent coagulation proteins in patients on VKAs, alterations in inflammatory signatures among CVST patients and a distinctive signature indicative of SARS-CoV-2 infection. However, no protein signature associated with a thromboembolic event could be identified neither in individual nor combined studies.

Conclusion

Although VKA treatment–specific and disease-specific signatures were captured, our study highlights that the challenges of discovering biomarkers in patients at risk of thromboembolic events lie in the heterogeneity of individual plasma profiles in relation to treatment and etiology.