What question did this study set out to answer?

To identify associations between factor XI clotting activity and plasma protein profiles in patients with venous thromboembolism to elucidate biological roles beyond coagulation.

June 13, 2022Scientific ReportsOpen Access

Association of FXI activity with thrombo-inflammation, extracellular matrix, lipid metabolism and apoptosis in venous thrombosis

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Why the study?

Preclinical and early human trials suggest FXIa inhibition prevents VTE and alleviates cytokine storm, supporting roles for FXI beyond coagulation that warranted exploration.

Population

Patients with acute VTE (n = 549) and at 12 months after (n = 187)

Comparison

Plasma protein profiling associated with varying FXI:C levels

Design

Observational cohort study using targeted proteomics and bioinformatics

Follow-up

12-months

Authors

ARAlejandro Pallares RoblesHeidelberg University VCVincent ten CateJohannes Gutenberg University Mainz ASAndreas SchulzUniversity of Stuttgart

Discussion

Member takes

Implication

FXI:C-protein associations in VTE are hypothesis-generating; leaves open whether FXIa inhibition modulates inflammation or outcomes beyond anticoagulation.

Key Points

To identify associations between factor XI clotting activity and plasma protein profiles in patients with venous thromboembolism to elucidate biological roles beyond coagulation.
Analyzed plasma samples from the GMP-VTE project during an acute venous thromboembolism event (n = 549) and at 12-month follow-up (n = 187).
Measured factor XI activity using a modified activated partial thromboplastin time assay and screened 444 plasma proteins using proximity extension assays, bioinformatics, and machine learning.
Identified 21 proteins significantly associated with factor XI activity during the acute event and 66 proteins at 12 months.
Found 7 proteins consistently associated with factor XI activity across both acute and 12-month evaluation time points.
Pathway analyses revealed that factor XI-associated proteins are enriched in biological processes governing thrombo-inflammation, extracellular matrix interactions, lipid metabolism, and apoptosis.

Structured PICO

Population

549 patients with an acute venous thromboembolism (VTE) event, with a subset of 187 patients evaluated at 12-months follow-up, from the Genotyping and Molecular Phenotyping of Venous Thromboembolism (GMP-VTE) Project.

Outcome

Associations between FXI activity (FXI:C) and the plasma protein profile (444 proteins investigated)surrogate

FXI activity is associated with plasma proteins enriched in immune pathways related to thrombo-inflammation, extracellular matrix interaction, lipid metabolism, and apoptosis in patients with VTE.

Cite This Study

Robles et al. (2022) studied this question.

synapsesocial.com/papers/6a911c99da08d7e10a830170 https://doi.org/10.1038/s41598-022-13174-5

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Implication

FXI:C-protein associations in VTE are hypothesis-generating; leaves open whether FXIa inhibition modulates inflammation or outcomes beyond anticoagulation.

Association of FXI activity with thrombo-inflammation, extracellular matrix, lipid metabolism and apoptosis in venous thrombosis

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Association of FXI activity with thrombo-inflammation, extracellular matrix, lipid metabolism and apoptosis in venous thrombosis

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider