Thromb Haemost 2017; 117(10): 1919-1929
DOI: 10.1160/TH17-02-0130
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

Neutrophil extracellular traps are increased in patients with acute ischemic stroke: prognostic significance

Juana Vallés
1  Hemostasis, Thrombosis, Atherosclerosis, and Vascular Biology Unit, Health Research Institute La Fe, Valencia, Spain
,
Aida Lago
2  Department of Neurology, University and Polytechnic Hospital La Fe, Valencia, Spain
,
María Teresa Santos
1  Hemostasis, Thrombosis, Atherosclerosis, and Vascular Biology Unit, Health Research Institute La Fe, Valencia, Spain
,
Ana María Latorre
1  Hemostasis, Thrombosis, Atherosclerosis, and Vascular Biology Unit, Health Research Institute La Fe, Valencia, Spain
,
José I. Tembl
2  Department of Neurology, University and Polytechnic Hospital La Fe, Valencia, Spain
,
Juan B. Salom
3  Cerebrovascular Research Joint Unit, Health Research Institute La Fe, Valencia, Spain
4  Department of Physiology, University of Valencia, Valencia, Spain
,
Candela Nieves
2  Department of Neurology, University and Polytechnic Hospital La Fe, Valencia, Spain
,
Antonio Moscardó
1  Hemostasis, Thrombosis, Atherosclerosis, and Vascular Biology Unit, Health Research Institute La Fe, Valencia, Spain
› Author Affiliations
Financial support: This work was supported in part by grants from the Spanish Fondo de Investigaciones Sanitarias Carlos III [FIS13/00016] Fondos FEDER, una forma de hacer Europa, Fundación Española de Trombosis y Hemostasia, Sociedad Valenciana de Cardiología, Consellería Valenciana d’Educació (ACIF/2016/465), GV and RETICS networks INVICTUS (RD12/0014/0004) and INVICTUS+ (RD16/0019/0008) ‘Instituto de Salud Carlos III’.
Further Information

Publication History

Received: 23 February 2017

Accepted after major revision: 16 June 2017

Publication Date:
28 November 2017 (online)

Summary

Neutrophil extracellular traps (NETs) are networks of DNA, histones, and proteolytic enzymes produced by activated neutrophils through different mechanisms. NET formation is promoted by activated platelets and can in turn activate platelets, thus favoring thrombotic processes. NETs have been detected in venous and arterial thrombosis, but data in stroke are scarce. The aim of this study was to evaluate NETs in the plasma of patients with acute ischemic stroke and their potential association with baseline clinical characteristics, stroke severity, and one-year clinical outcomes. The study included 243 patients with acute ischemic stroke. Clinical and demographic data and scores of stroke severity (NIHSS and mRs) at onset and discharge were recorded. Markers of NETs (cell-free DNA, nucleosomes, and citrullinated histone 3 (citH3)), were determined in plasma. Patients were followed-up for 12 months after the ischemic event. NETs were significantly elevated in the plasma of patients with acute ischemic stroke when compared to healthy subjects. NETs were increased in patients who were over 65 years of age and in those with a history of atrial fibrillation (AF), cardioembolic stroke, high glucose levels, and severe stroke scores at admission and discharge. In multivariate analysis, elevated levels of citH3, the most specific marker of NETs, at onset were independently associated with AF and all-cause mortality at oneyear follow-up. NETs play a role in the pathophysiology of stroke and are associated with severity and mortality. In conclusion, citH3 may constitute a useful prognostic marker and therapeutic target in patients with acute stroke.