{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T21:16:35Z","timestamp":1768338995798,"version":"3.49.0"},"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T00:00:00Z","timestamp":1639440000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Patients with chronic venous disease (CVD) have elevated levels of leucocyte elastase (LE) released from the activation of leucocytes. In acute deep venous thrombosis (DVT), LE can degrade fibrin from the thrombus resulting in cross-linked fibrin degradation products (E-XDP) being released into the bloodstream. In patients with CVD the levels and significance of circulating E-XDP are unknown. We aimed to investigate the association between plasma E-XDP concentration and severity of CVD. Levels of E-XDP were quantified with a specific enzyme-linked immunosorbent assay (ELISA) in plasma from 142 consecutively recruited CVD patients (mean age 64 years, (range 23\u201389), 81 were females and 61 males). Patients were also divided into three groups based on CVD severity using the C-class of the Clinical-Etiological-Anatomical-Pathophysiological (CEAP) classification, with C 0\u20131 class as the reference group, C 2\u20133 as the second group and C 4\u20136 as the third group with the most severely affected patients. We found significantly elevated levels of E-XDP in patients with C 4\u20136 compared with patients with C 0\u20131 (p = 0.007) and increased with increasing disease severity across the groups (p = 0.02). Significant independent association was observed between levels of E-XDP and the classes C 4\u20136 after adjustment for age and sex (p &lt; 0.05), but the association was no longer significant after further adjustment for use of statins, use of anticoagulants and history of DVT (p = 0.247). This exploratory study shows that E-XDP levels are elevated in patients with CVD, encouraging further studies on the role of E-XDP in CVD.<\/jats:p>","DOI":"10.1371\/journal.pone.0261073","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T18:41:42Z","timestamp":1639507302000},"page":"e0261073","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Plasma levels of leucocyte elastase-generated cross linked fibrin degradation products (E-XDP) are elevated in chronic venous disease"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9290-0393","authenticated-orcid":true,"given":"Helen","family":"Sinabulya","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Silveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena","family":"Blomgren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joy","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,12,14]]},"reference":[{"issue":"Suppl 1","key":"pone.0261073.ref001","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s12325-019-0881-7","article-title":"The Seriousness of Chronic Venous Disease: A Review of Real-World Evidence.","volume":"36","author":"AH Davies","year":"2019","journal-title":"Adv Ther."},{"key":"pone.0261073.ref002","article-title":"Global Epidemiology of Chronic Venous Disease: A Systematic Review with Pooled Prevalence Analysis","author":"S Salim","year":"2020","journal-title":"Ann Surg"},{"issue":"2","key":"pone.0261073.ref003","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.jvs.2008.09.014","article-title":"Updated terminology of chronic venous disorders: the VEIN-TERM transatlantic interdisciplinary consensus document","volume":"49","author":"B Eklof","year":"2009","journal-title":"Journal of vascular surgery"},{"issue":"3","key":"pone.0261073.ref004","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jvsv.2019.12.075","article-title":"The 2020 update of the CEAP classification system and reporting standards","volume":"8","author":"F Lurie","year":"2020","journal-title":"J Vasc Surg Venous Lymphat Disord"},{"issue":"4","key":"pone.0261073.ref005","doi-asserted-by":"crossref","first-page":"585","DOI":"10.5114\/ada.2021.108911","article-title":"Chronic venous disorders\u2014common and yet unknown\u2014a study of public awareness and primary symptoms in a selected group of patients.","volume":"38","author":"M Nowak","year":"2021","journal-title":"Postepy Dermatol Alergol"},{"issue":"4","key":"pone.0261073.ref006","doi-asserted-by":"crossref","first-page":"e123","DOI":"10.1016\/j.thromres.2013.01.011","article-title":"Negative impact of deep venous thrombosis on chronic venous disease","volume":"131","author":"FS Lozano S\u00e1nchez","year":"2013","journal-title":"Thrombosis Research"},{"issue":"4","key":"pone.0261073.ref007","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.ejvs.2014.12.031","article-title":"Epidemiological study on chronic venous disease in Belgium and Luxembourg: prevalence, risk factors, and symptomatology","volume":"49","author":"ME Vuylsteke","year":"2015","journal-title":"Eur J Vasc Endovasc Surg"},{"issue":"2","key":"pone.0261073.ref008","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1177\/1534734614535407","article-title":"Elevated Levels of Coagulation Factor VIII in Patients With Venous Leg Ulcers.","volume":"13","author":"PR Criado","year":"2014","journal-title":"Int J Low Extrem Wounds."},{"issue":"5","key":"pone.0261073.ref009","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/j.jvs.2008.12.017","article-title":"Higher prevalence of thrombophilia in patients with varicose veins and venous ulcers than controls","volume":"49","author":"KA Darvall","year":"2009","journal-title":"Journal of vascular surgery"},{"issue":"2","key":"pone.0261073.ref010","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.suc.2017.11.002","article-title":"Pathophysiology of Chronic Venous Disease and Venous Ulcers.","volume":"98","author":"JD Raffetto","year":"2018","journal-title":"Surg Clin North Am."},{"issue":"8","key":"pone.0261073.ref011","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1080\/10408363.2018.1529734","article-title":"D-dimer: Preanalytical, analytical, postanalytical variables, and clinical applications.","volume":"55","author":"J Favresse","year":"2018","journal-title":"Crit Rev Clin Lab Sci"},{"issue":"3","key":"pone.0261073.ref012","first-page":"546","article-title":"Association between statin use and plasma D-dimer levels. 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