Abstract Number: PB1036
Meeting: ISTH 2022 Congress
Theme: Coagulation and Natural Anticoagulants » Regulation of Coagulation
Background: Plasma cell-free DNA (cfDNA), derived from cellular death or neutrophil extracellular traps (NETs) is increased in patients with venous thromboembolism (VTE) and is associated with an increased risk of VTE. Other thrombotic disorders, like thrombotic microangiopathies, display increased plasma cfDNA through an impaired plasma DNaseI activity.
Aims: To ascertain whether increased plasma cfDNA in VTE patients may be mediated by lower DNaseI activity, measured with two functional assays.
Methods: We obtained plasma samples from 126 VTE patients and 79 healthy volunteers (controls). In patients, plasma samples were obtained between 6 and 24 months after the thrombotic event. cfDNA was quantified with PicoGreen (Life Technologies) and DNaseI activity was measured with two different assays: DNaseI assay Kit (Abcam) after optimization and the single radial enzyme-diffusion (SRED). Statistical analysis was performed with GraphPad (v.8.0.1).
Results: cfDNA levels were significantly increased in VTE patients (median 1799 ng/ml, 1st-3rd quartiles 1661-2088) than in controls (1632, 1185-1753) (P < 0.0001). However, DNaseI activity was also increased in VTE patients (5.814 μU/ml, 5.139-6.870) compared to controls (5.188, 4.794-6.217) (P=0.0041) when measured with the DNaseI assay Kit (Abcam); while, the increase was more discrete with the SRED method (0.49 cm2, 0.39-0.61 and 0.45, 0.36-0.52, respectively) (P=0.0512). cfDNA and DNaseI activity, measured by any method, did not inversely correlate, suggesting an independent mechanism for cfDNA increase.
Conclusion(s): Patients with VTE have long-lasting increased plasma levels of cfDNA and DNaseI activity. However, the increase in plasma cfDNA in VTE patients seems DNaseI-independent, evidenced by two different functional assays. We speculate that the increase in plasma DNaseI might be a protective mechanism against the presence of high cfDNA levels. ISCIII-FEDER (PI17/00495, PI20/00075, FI21/00171), GVA (ACIF/2017/138) and SETH.
To cite this abstract in AMA style:
Herranz R, Oto J, Plana E, Cana F, Fernández-Pardo A, Ferrando F, Cid A, Bonanad S, Medina P. The increase in plasma cell-free DNA in patients with venous thromboembolism is independent of DNaseI activity [abstract]. https://abstracts.isth.org/abstract/the-increase-in-plasma-cell-free-dna-in-patients-with-venous-thromboembolism-is-independent-of-dnasei-activity/. Accessed April 19, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/the-increase-in-plasma-cell-free-dna-in-patients-with-venous-thromboembolism-is-independent-of-dnasei-activity/