ORIGINAL RESEARCH article
Front. Physiol.
Sec. Vascular Physiology
Neutrophil Extracellular Trap Markers Predict Thrombotic Risk in Patients with Hyperhomocysteinemia: Development and Validation of a Predictive Model
Provisionally accepted
- 1Shandong Second Medical University, Weifang, China
- 2Weifang People's Hospital, Weifang, China
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Background:Venous thromboembolic diseases pose a serious threat to human health, and their pathogenesis is closely associated with the abnormal activation of neutrophils and neutrophil extracellular traps (NETs). However, the mechanisms underlying the role of NETs in thrombosis related to Hyperhomocysteinemia (hHcy) remain unclear. In this study, we systematically investigated the correlation between NETs and hHcy-associated thrombosis by measuring key NETs markers (myeloperoxidase, MPO; citrullinated histone H3, CitH3) and cell-free DNA (cfDNA) levels. Based on multivariate analysis, we developed and validated a thrombotic risk prediction model integrating clinical indicators and NETs markers, providing novel biomarkers and an assessment tool for early clinical identification of high-risk patients. Result: Laboratory test results revealed significantly elevated levels of NETs-related markers in the peripheral blood of DVT patients, including Myeloperoxidase-Deoxyribonucleic Acid (MPO-DNA), CitH3, cfDNA, and absolute neutrophil count. Multivariate logistic regression analysis confirmed that MPO-DNA (Odds Ratio, OR=11.58, 95% CI: 3.75–35.73, Probability Value, p<0.001), CitH3 (OR=1.11, 95% CI: 1.05–1.17, p<0.001), cell-free DNA (OR=1.02, 95% Confidence Interval, 95% CI: 1.01–1.02, p<0.001), and neutrophil (OR=1.67, 95% CI: 1.14–2.44, p=0.008) were all independent risk factors for DVT in hHcy patients. The risk prediction model constructed based on these factors demonstrated excellent discriminative performance, with area under the receiver operating characteristic curve values of 0.93 (95% CI: 0.88–0.99) in the training cohort and 0.96 (95% CI: 0.88–1.00) in the validation cohort. Conclusion: This study demonstrates that hHcy-associated thrombosis is significantly correlated with elevated levels of NETs. Based on these findings, we have developed a novel non-invasive thrombotic risk prediction model that can effectively identify high-risk hHcy patients.
Keywords: DVT, Hyperhomocysteinemia, NEtosis, NETs, nomogram
Received: 29 Aug 2025; Accepted: 27 Nov 2025.
Copyright: © 2025 Shao, Zhang, Wang, Pei, Jiang and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Guangxin Cao
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