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

Abstract

Background The intraluminal thrombi (ILT) of abdominal aortic aneurysms (AAA) contain neutrophils, which can secrete elastase. We evaluated whether plasma neutrophil elastase-derived cross-linked fibrin degradation products (E-XDP) could reveal the presence, size and mechanical stress of AAAs and its ILTs.

Methods E-XDP and D-dimer were measured in plasma from 37 male patients with AAA and 42 male controls. The ILT volumes of the AAAs and any coexisting aneurysms could be measured in 29 patients and finite element analysis was performed to estimate mechanical stress of the ILT. E-XDP, neutrophil elastase and neutrophil marker CD66acd were evaluated in aortic tissue with immunohistochemistry (IHC). The association between ILT volume and E-XDP was validated in a separate cohort (n = 51).

Results E-XDP levels were elevated in patients with AAA compared with controls (p = 5.8e-13), indicated AAA with 98% sensitivity, 86% specificity and increased with presence of coexisting aneurysms. The association between AAA and increased E-XDP was independent of smoking, comorbidities and medication. E-XDP correlated with volume of all ILTs (r = 0.76, p = 4.5e-06), mean ILT stress (r = 0.46, p = 0.013) and the volume of the AAA-associated ILT (r = 0.64, p = 0.00017). E-XDP correlated stronger with ILT volume compared with D-dimer (r = 0.76 vs. r = 0.64, p = 0.018). The correlation between E-XDP and ILT volume was validated in the separate cohort (r = 0.53, p = 7.6e-05). IHC revealed E-XDP expression in the ILT, spatially related to neutrophil elastase and neutrophils.

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

Keywords

thrombus - leukocyte elastase - aortic aneurysm - abdominal - finite element analysis - computed tomography

Authors' Contributions

Conception and design: M.L.L., A.S., R.H., P.E., J.R.

Analysis and interpretation: M.L.L., A.S., P.E., J.R.

Data collection: M.L.L., A.S., J.E.

Writing the article: M.L.L., A.S., P.E., J.R.

Critical revision of the article: M.L.L., A.S., R.H., S.F., M.L., J.E., T.C.G., P.E., J.R.

Final approval of the article: M.L.L., A.S., R.H., S.F., M.L., J.E., T.C.G., P.E., J.R.

Statistical analysis: M.L.L., R.H., A.S., J.R.

Obtained funding: R.H., T.C.G., P.E., J.R.

Overall responsibility: J.R.

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