Background: Thrombosis is frequently manifested in critically ill patients with systemic inflammation, including sepsis. The coagulopathy in systemic inflammation is often associated with increased levels of fibrinogen and D-dimer. There are studies that have reported elevated levels of vimentin in serum/plasma of septic patients.

Aims: We sought to investigate the relationship between vimentin and fibrinogen in fibrin polymerization.

Methods: We measured vimentin levels in plasma from healthy subjects and critically ill patients with systemic inflammation. We used recombinant vimentin protein to conduct biochemical studies and fibrin formation assays. Anti-vimentin antibodies were used to analyze fibrin polymerization and fibrinolysis assays, to analyze fibrin clot structure using confocal microscopy, and for co-immunoprecipitation studies. Size exclusion chromatography was utilized to isolate extracellular vimentin from plasma.

Results: The levels of vimentin in plasma derived from critically ill subjects with sepsis were in average three-fold higher value compared to that of healthy subjects. We determined that vimentin interacts directly with fibrinogen and enhances fibrin formation. Anti-vimentin antibody effectively blocked fibrin formation and caused changes in the fibrin structure in plasma. Additionally, confocal imaging demonstrated plasma vimentin enmeshed in the fibrin fibrils. Co-immunoprecipitation assays demonstrated a direct interaction between extracellular vimentin and fibrinogen in plasma from critically ill patients but not in healthy plasma. Lastly, in contrast to healthy plasma, vimentin in plasma from critically ill patients co-eluted with fibrinogen from the size exclusion column chromatography.

Conclusion(s): This study describes a novel role for extracellular vimentin in regulating fibrin formation and clot structure. The data suggest that elevated levels of an aberrant extracellular vimentin in critically ill patients with systemic inflammation potentiates fibrin clot formation; being consistent with the notion that plasma vimentin may contribute to the pathogenesis of thrombosis.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/the-role-of-extracellular-vimentin-in-fibrin-formation/