Circulating Nucleosomes and Neutrophil Activation As Risk Factors for Deep Vein Thrombosis

The formation of neutrophil extracellular traps (NETs) and the exposure of nucleosomes on these NETs contribute to coagulation activation and the propagation of deep vein thrombosis (DVT) in animal models. However, no data is available on the role of NETs or nucleosomes in patients with thrombosis.

We conducted a case-control study, in which levels of circulating nucleosomes and neutrophil elastase–α1-antitrypsin (EA) complexes were assessed in plasma from 150 patients with objectified symptomatic DVT (cases) and compared with 195 patients with a clinical suspicion of DVT, but in whom DVT was excluded (controls). We explored the association between both nucleosomes and EA complexes, and the presence of DVT by calculating the odds ratio (OR) with corresponding 95% confidence intervals (CI). Elevated levels of both circulating nucleosomes and EA complexes were associated with a 3-fold risk of DVT, and the associations remained similar after adjustment for potential confounders (malignancy, smoking, recent immobilization, recent hospitalization). The risk increased with higher nucleosome and EA complex levels, suggesting a dose-dependent relationship between circulating nucleosomes, activated neutrophils and DVT.

Circulating nucleosomes and activated neutrophils contribute to the development of DVT in humans and might have implications for treatment and prevention.

No relevant conflicts of interest to declare.