Neutrophil Elastase-Derived Fibrin Degradation Products Indicate Presence of Abdominal Aortic Aneurysms and Correlate with Intraluminal Thrombus Volume

Liljeqvist, Moritz Lindquist; Silveira, Angela; Hultgren, Rebecka; Frebelius, Siw; Lengquist, Mariette; Engström, Jan; Gasser, Thomas C.; Eriksson, Per; Roy, Joy

doi:10.1160/th17-05-0348

Cited by 11 publications

(8 citation statements)

References 352 publications

(589 reference statements)

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“…Because leucocyte activation with consequent release of elastin has been shown to participate in the pathophysiology of CVD, it would be reasonable to assume that E-XDP determination would be more specific for CVD than D-dimer. Of note, the assay used in the present study was proven specific for measuring levels of E-XDP generated from fibrin by the proteolytic action of LE (and not plasmin) by Kohno et al and in a study done by our group [ 16 , 18 ].…”

Section: Discussionmentioning

confidence: 92%

“…Besides activation of leukocytes, it is possible that the patients have thrombi in other parts of the body or micro thrombi in the vein wall that are also degraded by LE, but other unknown sources of thrombi can not be excluded [ 14 , 23 ]. For example, in a previous study by our group, we observed an association between E-XDP and presence of intraluminal thrombi in patients with abdominal aortic aneurysms [ 18 ].…”

Section: Discussionmentioning

confidence: 93%

“…This enzyme degrades cross-linked fibrin specifically, in sites different from those hydrolyzed by plasmin, producing fibrin degradation products known as E-XDP which are structurally different from D-dimers [ 15 , 16 ]. Circulating levels of E-XDP have previously been observed to be elevated in patients with DVT and abdominal aortic aneurysms with large intraluminal thrombi [ 17 , 18 ], however to our knowledge no such study has been performed on CVD patients to date.…”

Section: Introductionmentioning

confidence: 99%

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Plasma levels of leucocyte elastase-generated cross linked fibrin degradation products (E-XDP) are elevated in chronic venous disease

et al. 2021

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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 23–89), 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 0–1 class as the reference group, C 2–3 as the second group and C 4–6 as the third group with the most severely affected patients. We found significantly elevated levels of E-XDP in patients with C 4–6 compared with patients with C 0–1 (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 4–6 after adjustment for age and sex (p < 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.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Plasma levels of leucocyte elastase-generated cross linked fibrin degradation products (E-XDP) are elevated in chronic venous disease

et al. 2021

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“…showed that E-XDP, neutrophil elastase had higher concentrations in patients with the presents of AAA and other coexisting aneurysms but popliteal artery aneurysms weren´t specifically studied. 41 The presence of AAAs associated with growth rate could be a surrogate marker for the presence of a more generalized aneurysmal disease and has not been shown by others.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 95%

Natural history, growth rates, and treatment of popliteal artery aneurysms

Jergovic

Cheesman

Siika

et al. 2022

Journal of Vascular Surgery

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“…Besides, there is a direct correlation between elastase activity and nicotine concentration [ 114 ]. Recently, studies showed that circulating NE-derived fibrin degradation products are elevated in patients with AAA and correlate with AAA and ILT volume as well as with the mechanical stress of the ILT [ 115 , 116 ]. The role of NE as a postoperative biomarker is controversial.…”

Section: Abdominal Aortic Aneurysms and Neutrophilsmentioning

confidence: 99%

Neutrophils as Regulators and Biomarkers of Cardiovascular Inflammation in the Context of Abdominal Aortic Aneurysms

et al. 2021

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Neutrophils represent up to 70% of circulating leukocytes in healthy humans and combat infection mostly by phagocytosis, degranulation and NETosis. It has been reported that neutrophils are centrally involved in abdominal aortic aneurysm (AAA) pathogenesis. The natural course of AAA is growth and rupture, if left undiagnosed or untreated. The rupture of AAA has a very high mortality and is currently among the leading causes of death worldwide. The use of noninvasive cardiovascular imaging techniques for patient screening, surveillance and postoperative follow-up is well established and recommended by the current guidelines. Neutrophil-derived biomarkers may offer clinical value to the monitoring and prognosis of AAA patients, allowing for potential early therapeutic intervention. Numerous promising biomarkers have been studied. In this review, we discuss neutrophils and neutrophil-derived molecules as regulators and biomarkers of AAA, and our aim was to specifically highlight diagnostic and prognostic markers. Neutrophil-derived biomarkers may potentially, in the future, assist in determining AAA presence, predict size, expansion rate, rupture risk, and postoperative outcome once validated in highly warranted future prospective clinical studies.

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Neutrophil Elastase-Derived Fibrin Degradation Products Indicate Presence of Abdominal Aortic Aneurysms and Correlate with Intraluminal Thrombus Volume

Abstract: E-XDP is a marker of the presence of AAA and coexisting aneurysms as well as the volume and mechanical stress of the ILT.

Cited by 11 publications

References 352 publications

Plasma levels of leucocyte elastase-generated cross linked fibrin degradation products (E-XDP) are elevated in chronic venous disease

Plasma levels of leucocyte elastase-generated cross linked fibrin degradation products (E-XDP) are elevated in chronic venous disease

Natural history, growth rates, and treatment of popliteal artery aneurysms

Neutrophils as Regulators and Biomarkers of Cardiovascular Inflammation in the Context of Abdominal Aortic Aneurysms

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