Correlation of Neutrophil to Lymphocyte Ratio with Expression of Neutrophil Extracellular Traps Within Stroke Emboli

2021 ◽  
pp. 159101992110655
Author(s):  
Jorge Arturo Larco ◽  
Mehdi Abbasi ◽  
Sarosh Irfan Madhani ◽  
Madalina Oana Mereuta ◽  
Yang Liu ◽  
...  

Background & Purpose It has been hypothesized that circulating neutrophils have a direct correlation with the composition of emboli in acute ischemic stroke (AIS). The aim of this study is to evaluate the association between neutrophil-lymphocyte ratio (NLR) in peripheral blood and the expression of neutrophil extracellular traps (NETs) within stroke emboli. Methods Consecutive patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) that underwent mechanical thrombectomy (MT) were included. Patients were divided into two groups based on NLR median value. Retrieved thrombi were histologically analyzed using Martius Scarlett Blue (MSB) for main thrombus components including red blood cells (RBCs), white blood cells (WBCs), fibrin and platelet. Immunohistochemistry staining for von Willebrand Factor (vWF) and anti-citrullinated H3 (H3Cit; NETs marker) was also performed. Results Samples from a total of 84 patients were included. The average percentage of RBCs, WBCs, fibrin, platelet, H3Cit, and vWF components in thrombi were 45.1%, 3.5%, 21.8%, 29.6%, 19.7% and 14.8% respectively. When stratifying by NLR group [low (≤3.94) versus high (>3.95)], high NLR group had significantly more WBCs (4.5%), fibrin (24.2%), H3Cit (22.7%) and vWF (17.1%) thrombus fractions compared to low NLR group. Additionally, RBC content (38.8%) was lower in the high NLR group. Conclusions NLR is correlated with the amounts of WBCs, fibrin, NETs and vWF within the thrombi retrieved from AIS patients due to LVO.

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Wei Li ◽  
Huan Wang ◽  
Wuwei Feng ◽  
Meng Zhang

Introduction: Neutrophil extracellular traps (NETs) are composed mainly of strands of filamentous DNA and nuclear proteins, such as chromatin or isoforms of histone and secretable neutrophil granular proteins. Recent studies have shown that NETs existed in the venous thrombi and might function as a scaffold and had implication for thrombolytic treatments. Hypothesis: NETs also exists in cerebral arterial thrombus collected from patients with acute ischemic stroke(AIS). Methods: Ten arterial thrombi were collected from 10 AIS patients (33-78 years old, 4 females) who were treated by endovascular therapy (eight of them accepted alteplase thrombolysis firstly)within 8 hours after symptoms onset. Hematoxylin-eosin (HE) staining, immunofluorescence staining (including anti-histone H3 and Hoechst 33342 which label DNA) and electron microscopy were performed to identify the existence of fibrin and/or NETs in thrombus. Results: There were 4 thrombi from middle cerebral artery, 3 from internal carotid artery and 3 from basilar artery. Cardioembolism were considered as etiology for 5 patients and large artery atherosclerosis was the etiology for another 5 patients. HE staining showed that large amounts of fibrin and white blood cells in all ten cerebral arterial thrombi. NETs structures were also identified in 10/10 cerebral arterial thrombi by immunofluorescence staining. Furthermore, the existence of neutrophil-released DNA network together with fibrin was confirmed using electron microscopy in all 10 thrombi. Conclusion: Our results directly demonstrated that NETs do exist in the arterial thrombi from patients with AIS. they may serve as another structural component in addition to fibrin in both cardiogenic and artery atherosclerotic thrombi. NETs can be a new potential target for the recanalization treatment. Keyword: Neutrophil extracellular traps (NETs); arterial thrombus; Acute ischemic stroke


Stroke ◽  
2018 ◽  
Vol 49 (3) ◽  
pp. 754-757 ◽  
Author(s):  
Celina Ducroux ◽  
Lucas Di Meglio ◽  
Stephane Loyau ◽  
Sandrine Delbosc ◽  
William Boisseau ◽  
...  

2020 ◽  
Author(s):  
Pengyu Gong ◽  
Yukai Liu ◽  
Yachi Gong ◽  
Gang Chen ◽  
Xiaohao Zhang ◽  
...  

Abstract Background and Purpose: To investigate the association of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR) with post-thrombolysis early neurological outcomes including early neurological improvement (ENI) and early neurological deterioration (END) in patients with acute ischemic stroke (AIS).Methods: AIS patients undergoing intravenous thrombolysis were enrolled from April 2016 to September 2019. Blood cell counts were sampled before thrombolysis. Post-thrombolysis END was defined as National Institutes of Health Stroke Scale (NIHSS) score increase of ≥4 within 24 hours after thrombolysis. Post-thrombolysis ENI was defined as NIHSS score decrease of ≥4 or complete recovery within 24 hours. Multivariable logistic regression analyses were performed to explore the relationship of NLR, PLR and LMR to post-thrombolysis END and ENI. We also used receiver operating characteristic curve analysis to assess the discriminative ability of three ratios in predicting END and ENI.Results: Among 1060 recruited patients, a total of 193 (18.2%) were diagnosed with ENI and 398 (37.5%) were diagnosed with END. Multivariable logistic models indicated that NLR (odds ratio [OR], 1.652; 95% confidence interval [CI] 1.510-1.807, P=0.001) and PLR (OR, 1.015; 95% CI 1.012-1.018, P=0.001) were independent factors for post-thrombolysis END. Moreover, NLR (OR, 0.686; 95% CI 0.631-0.745, P=0.001), PLR (OR, 0.997; 95% CI 0.994-0.999, P=0.006) and LMR (OR, 1.170; 95% CI 1.043-1.313, P=0.008) served as independent factors for post-thrombolysis ENI. Area under curve (AUC) of NLR, PLR and LMR to discriminate END were 0.763, 0.703 and 0.551, respectively. AUC of NLR, PLR and LMR to discriminate ENI were 0.695, 0.530 and 0.547, respectively.Conclusions: NLR and PLR were associated with and may predict post-thrombolysis END. NLR, PLR and LMR were related to post-thrombolysis ENI.


2015 ◽  
pp. 50-54
Author(s):  
V. V. Zhelezko ◽  
I. A. Novikova

The article presents the results of the assessment of functional features of neutrophils in 34 patients with rheumatoid arthritis. The study revealed a decrease in absorbing and oxygen producing activity associated with the increased formation of neutrophil extracellular traps (NET) and the dependence of parameters of NET forming activity of white blood cells on the rheumatoid factor, as well as the dependence of spontaneous oxygen producing activity on the functional class and the disease development.


2021 ◽  
Vol 16 (1) ◽  
pp. 1365-1376
Author(s):  
Yiping Cheng ◽  
Wenhao Yu ◽  
Yuping Zhou ◽  
Tao Zhang ◽  
Haiyan Chi ◽  
...  

Abstract The role of inflammation has been identified in the pathogenesis of diabetic ketoacidosis (DKA). The neutrophil/lymphocyte ratio (NLR) and white blood cells (WBC) can be used to predict a systemic inflammatory response. Changes in NLR and WBC levels have never been explored in type 1 diabetes mellitus (T1DM) patients with DKA and an uninfected state. This retrospective study included a total of 644 participants. NLR and WBC were measured in the control group (n = 316) and in T1DM patients with mild-DKA (n = 92), severe-DKA (n = 52), and non-DKA (n = 184) in an uninfected state. Then, we assessed the independent predictors of DKA occurrence in T1DM patients in an uninfected state. The diagnostic performance of variables was determined by receiver operating characteristic curve analysis. Serum NLR of T1DM patients is significantly higher than that of normal controls, and if DKA occurs, NLR increases further and increases with the severity of DKA. In addition to diastolic blood pressure, blood urea nitrogen, glycated hemoglobin (HbA1c), and WBC, NLR was also independently associated with DKA in T1DM patients with an uninfected state (OR = 1.386, 95% CI: 1.127–1.705, p = 0.002). Furthermore, the diagnosis analysis showed that except for NLR and WBC, the area under the curve (AUC) of indicators with a statistical difference in patients with and without DKA were 0.747 for DKA diagnosis, and after the addition of NLR and WBC, the AUC was 0.806. The increased NLR level represents a low-cost and highly accessible predictor for DKA in T1DM patients with an uninfected state. The addition of inflammation indicators can play a statistically significant role in the prediction model of the DKA occurrence.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qun Gao ◽  
Shen Hu ◽  
Ximeng Yang ◽  
Junjie Wang ◽  
Jun Lu ◽  
...  

Abstract Background The significance of carotid webs (CaWs) in ischemic stroke is becoming acknowledged. Histological features of clot composition in situ and secondary cerebrovascular embolized thrombi caused by CaW have not been described concurrently. Understanding clots’ histological composition is essential for understanding the pathophysiology of clot formation in CaW. Case presentation A 50-year-old male patient with acute ischemic stroke, which was believed to be caused by ipsilateral CaW, was admitted to the hospital. Mechanical thrombectomy was used to retrieve thromboemboli from the middle cerebral artery. One month thereafter, the patient underwent carotid endarterectomy, and in situ CaW thrombi were retrieved. Histological analysis by hematoxylin and eosin staining revealed that histopathologic embolized thrombi appeared as typical mixed thrombi, 46.03% fibrin/platelet ratio, 48.12% RBCs, and 5.85% white blood cells. In situ thrombi had a higher fibrin/platelet ratio (68.0%), fewer RBCs (17.2%), and 14.8% white blood cells. Conclusion The histopathology of large vessel occlusion stroke embolized thrombi by CaW is similar to that of other stroke etiologies. However, the clot composition of embolized thrombi significantly differs from that of in situ thrombi. CaW’s in situ thrombi showed predominantly fibrin, and embolized thrombi had equivalent contents of red blood cells and fibrin/platelets. Histopathological differences between in situ and embolized thrombi suggest new research directions for the etiology of embolization. Further studies are required to confirm these results.


2017 ◽  
Vol 117 (10) ◽  
pp. 1919-1929 ◽  
Author(s):  
Juana Vallés ◽  
María Teresa Santos ◽  
Ana María Latorre ◽  
José Tembl ◽  
Juan Salom ◽  
...  

SummaryNeutrophil 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.


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