Circulating DNAs, a Marker of Neutrophil Extracellular Traposis and Cancer-Related Stroke

Bang, Oh Young; Chung, Jong Won; Cho, Yeon Hee; Oh, Min‐Jeong; Seo, Woo Keun; Kim, Gyeong Moon; Ahn, Myung Ju

doi:10.1161/strokeaha.119.026373

Cited by 48 publications

(39 citation statements)

References 13 publications

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“…48 Our study and other studies showed that NETosis markers (e.g., circulating DNAs and citrullinated histone H2) were increased in patients with cancer-related stroke. 49,50 Increased circulating cancer cell-derived EVs could increase the formation of NETs in cancer-associated thrombosis. 49,51 Neutrophils, upon activation, release de-condensed chromatin for the formation of NETs, that promote thrombosis by the formation of a scaffold for adhesion of platelets, red blood cells, and platelet adhesion molecules such as fibrinogen, and activate both intrinsic and extrinsic coagulation pathways.…”

Section: Pathomechanisms Of Cancercoagulopathymentioning

confidence: 99%

Cancer-Related Stroke: An Emerging Subtype of Ischemic Stroke with Unique Pathomechanisms

et al. 2020

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Systemic cancer and ischemic stroke are common conditions and two of the most frequent causes of death among the elderly. The association between cancer and stroke has been reported worldwide. Stroke causes severe disability for cancer patients, while cancer increases the risk of stroke. Moreover, cancer-related stroke is expected to increase due to advances in cancer treatment and an aging population worldwide. Because cancer and stroke share risk factors (such as smoking and obesity) and treatment of cancer can increase the risk of stroke (e.g., accelerated atherosclerosis after radiation therapy), cancer may accelerate conventional stroke mechanisms (i.e., atherosclerosis, small vessel disease, and cardiac thrombus). In addition, active cancer and chemotherapy may enhance thrombin generation causing stroke related to coagulopathy. Patients with stroke due to cancer-related coagulopathy showed the characteristics findings of etiologic work ups, D-dimer levels, and infarct patterns. In this review, we summarized the frequency of cancer-related stroke among patients with ischemic stroke, mechanisms of stroke with in cancer patients, and evaluation and treatment of cancer-related stroke. We discussed the possibility of cancer-related stroke as a stroke subtype, and presented the most recent discoveries in the pathomechanisms and treatment of stroke due to cancer-related coagulopathy.

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Section: Pathomechanisms Of Cancercoagulopathymentioning

confidence: 99%

Cancer-Related Stroke: An Emerging Subtype of Ischemic Stroke with Unique Pathomechanisms

et al. 2020

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“…For example, the OASIS-Cancer study reported that patients with cancer and cryptogenic ischemic stroke have increased blood levels of extracellular vesicles and neutrophil extracellular trap formation (NETosis) than control patients. 14,15 Although both of these pathophysiological mechanisms are linked to hypercoagulability, their reproducibility and scalability may limit their clinical use. Furthermore, several studies have reported that plasma D-dimer levels are increased in patients with cancer and stroke, but D-dimer is a nonspecific fibrin degradation product and can be increased by stroke itself and in patients with cardiac disease.…”

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confidence: 99%

Mechanisms of Ischemic Stroke in Patients with Cancer: A Prospective Study

Navi

Sherman

Genova

et al. 2021

Annals of Neurology

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The objective of this study was to examine the pathophysiology of ischemic stroke with cancer. Methods: We conducted a prospective cross-sectional study from 2016 to 2020 at 2 hospitals. We enrolled 3 groups of 50 adult participants each. The main group included patients with active solid tumor cancer and acute ischemic stroke. The control groups included patients with acute ischemic stroke only or active cancer only. The patients with stroke-only and patients with cancer-only were matched to the patients with cancer-plus-stroke by age, sex, and cancer type, if applicable. The outcomes were prespecified hematological biomarkers and transcranial Doppler microemboli detection. Hematological biomarkers included markers of coagulation (D-dimer and thrombin-antithrombin), platelet function (P-selectin), and endothelial integrity (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], and soluble vascular cell adhesion molecule-1 [sVCAM-1]). Hematological biomarkers were compared between groups using the Kruskal-Wallis and Wilcoxon Rank-Sum tests. In multivariable linear regression models, we adjusted for race, number of stroke risk factors, smoking, stroke severity, and antithrombotic use. Transcranial Doppler microemboli presence was compared between groups using chi-square tests.Results: Levels of all study biomarkers were different between groups. In univariate between-group comparisons, patients with cancer-plus-stroke had higher levels of D-dimer, sICAM-1, sVCAM-1, and thrombomodulin than both control groups; higher levels of thrombin-antithrombin than patients with cancer-only; and higher levels of P-selectin than patients with stroke-only. Findings were similar in multivariable analyses. Transcranial Doppler microemboli were detected in 32% of patients with cancer-plus-stroke, 16% of patients with stroke-only, and 6% of patients with canceronly (p = 0.005). Interpretation: Patients with cancer-related stroke have higher markers of coagulation, platelet, and endothelial dysfunction, and more circulating microemboli, than matched controls.

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“…27 Cancer directly stimulates neutrophils to release decondensed chromatin, leading to the formation of neutrophil extracellular traps (NETs) that promote microthrombosis. 23,28 Thrombus in CRIS was also shown to be platelet-rich, which further confirmed that cancer cell may activate platelets, trigger thrombosis, and eventually lead to ischemic stroke. 29,30 The present study showed that BCRIS patients had significantly higher platelets counts and triggered thrombosis by increased platelets, which played a role in BCRIS occurrence.…”

Section: Discussionmentioning

confidence: 67%

“…Several animal studies showed that cancer cells can release extracellular vesicles into the circulating blood, leading to an increase in D-dimer levels and further triggering the development of microthrombosis, which suggests that cancer could lead to CRIS through the hypercoagulability pathway. 15,23 Previous studies showed that elevated serum D-dimer levels were associated with hypercoagulability and CRIS. 5,24 Seok et al 24 reported that the elevated Ddimer level was linearly correlated with the increase in microthrombus signals that were detected by superior and Doppler ultrasound of the internal carotid artery in stroke patients with active cancer; this further confirmed the association between hypercoagulability and CRIS.…”

Section: Discussionmentioning

confidence: 99%

Independent risk factors and the potential predictors of bladder cancer-related ischemic stroke

Quan

Qin

et al. 2020

J Int Med Res

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Objective To investigate the independent risk factors and potential predictors of bladder cancer-related ischemic stroke (BCRIS). Methods This was a multi-center retrospective study including patients with active bladder cancer and acute ischemic stroke without traditional stroke risk factors (BCRIS group), and sex- and age-matched patients with active bladder cancer alone (control group). Data were collected between January 2006 and December 2018. Uni- and multivariate analyses were performed to identify independent risk factors for BCRIS. The predictive performance of these risk factors was assessed using receiver operating characteristic (ROC) curves. Results Records were retrospectively reviewed from 60 BCRIS patients and 120 bladder cancer controls. Univariate analysis revealed that serum D-dimer and carcinoembryonic antigen (CEA) levels and the platelet and neutrophil counts were significantly higher in BCRIS patients compared with controls. Multivariate analysis identified the three above-mentioned variables as independent risk factors for BCRIS. The product of all three factors gave the largest area under the ROC curve. Conclusions Elevated serum D-dimer and CEA levels and increased platelet count were independent risk factors for BCRIS, and the cut-off value based on the product of the three independent risk factors (≥2,640,745.29) could serve as a potential predictor of BCRIS.

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Circulating DNAs, a Marker of Neutrophil Extracellular Traposis and Cancer-Related Stroke

Cited by 48 publications

References 13 publications

Cancer-Related Stroke: An Emerging Subtype of Ischemic Stroke with Unique Pathomechanisms

Cancer-Related Stroke: An Emerging Subtype of Ischemic Stroke with Unique Pathomechanisms

Mechanisms of Ischemic Stroke in Patients with Cancer: A Prospective Study

Independent risk factors and the potential predictors of bladder cancer-related ischemic stroke

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