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

Abstract

3387 Objective: 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. Methods and results: 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. Conclusions: Circulating nucleosomes and activated neutrophils contribute to the development of DVT in humans and might have implications for treatment and prevention. Disclosures: No relevant conflicts of interest to declare.

Integrated GWAS and Gene Expression Suggest ORM1 as a Potential Regulator of Plasma Levels of Cell-Free DNA and Thrombosis Risk

“…11 12 13 Accordingly, cfDNA levels have been found elevated in deep vein thrombosis (DVT) both in animals and humans. 11 14 15 16 Furthermore, in vivo DNase 1 treatment is effective in eliminating cfDNA from the blood stream and prevent DVT in mice. 16 Also, elevated levels of cfDNA have been able to predict mortality in venous thrombosis (VT) patients aged >65 years.…”

Multiallelic Copy Number Variation in ORM1 is Associated with Plasma Cell-Free DNA Levels as an Intermediate Phenotype for Venous Thromboembolism

“…15 16 There is evidence that NET components are present in human venous thrombi and are present at elevated levels in the plasma of DVT patients. 18 19 20 21 Therefore, NET biomarkers could be used as quantitative intermediate phenotypes of VTE. Specifically, cell-free DNA (cfDNA) levels have been analyzed as an unspecific marker of NETs in both animal and human studies of DVT.…”