scholarly journals Pharmacological Modulation of Neutrophil Extracellular Traps Reverses Thrombotic Stroke tPA (Tissue-Type Plasminogen Activator) Resistance

Stroke ◽  
2019 ◽  
Vol 50 (11) ◽  
pp. 3228-3237 ◽  
Author(s):  
Carolina Peña-Martínez ◽  
Violeta Durán-Laforet ◽  
Alicia García-Culebras ◽  
Fernando Ostos ◽  
Macarena Hernández-Jiménez ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Neutrophil Extracellular Traps ◽  
Dnase I ◽  
Tissue Type ◽  
Stroke Patients ◽  
Tissue Type Plasminogen Activator ◽  
Pharmacological Modulation ◽  
Extracellular Traps ◽  
Type Plasminogen Activator ◽  
Photothrombotic Stroke

Background and Purpose— Recanalization of the occluded artery is a primary goal in stroke treatment. Unfortunately, endovascular treatment is not always available, and tPA (tissue-type plasminogen activator) therapy is limited by its narrow therapeutic window; importantly, the rate of early arterial recanalization after tPA administration is low, especially for platelet-rich thrombi. The mechanisms for this tPA resistance are not well known. Since neutrophil extracellular traps (NETs) have been implicated in this setting, our aim was to study whether NET pharmacological modulation can reverse tPA resistance and the role of TLR4 (Toll-like receptor 4), previously related to NET formation, in thrombosis. Methods— To this goal, we have used a mouse photothrombotic stroke model, which produces a fibrin-free thrombus composed primarily of aggregated platelets and thrombi obtained from human stroke patients. Results— Our results demonstrate that (1) administration of DNase-I, which promotes NETs lysis, but not of tPA, recanalizes the occluded vessel improving photothrombotic stroke outcome; (2) a preventive treatment with Cl-amidine, impeding NET formation, completely precludes thrombotic occlusion; (3) platelet TLR4 mediates NET formation after photothrombotic stroke; and (4) ex vivo fresh platelet-rich thrombi from ischemic stroke patients are effectively lysed by DNase-I. Conclusions— Hence, our data open new avenues for recanalization of platelet-rich thrombi after stroke, especially to overcome tPA resistance.

Abstract TMP19: Intravenous Recombinant Tissue-type Plasminogen Activator Use in Young Adults With Acute Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jodi A Dodds ◽  
Ying Xian ◽  
Shubin Sheng ◽  
Gregg Fonarow ◽  
Ronald A Matsouaka ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Older Patients ◽  
Young Patients ◽  
Tissue Type ◽  
Stroke Patients ◽  
Younger Patients ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

Background: Intravenous recombinant tissue-type plasminogen activator (rt-PA) administration improves outcomes in acute ischemic stroke. However, young patients (<40 years old) presenting with stroke symptoms may experience delays in treatment due to misdiagnosis or a reluctance to treat since they do not fit the profile of a typical stroke patient. Methods: We analyzed data from the large national Get With The Guidelines–Stroke registry for acute ischemic stroke patients hospitalized between January 2009 and September 2015. Multivariable models with generalized estimating equations (GEE) were used to test for differences between younger (age 18-40) and older (age > 40) acute ischemic stroke patients, controlling for patient and hospital characteristics including stroke severity. Results: Of 1,320,965 AIS patients admitted to participating hospitals, 2.3% (30,448) were aged 18-40. Among these patients, 12.5% received rt-PA versus 8.8% of those aged >40 (p<0.001). Of patients arriving within 3.5 hours of symptom onset without contraindications, 68.7% of younger patients received IV rt-PA versus 63.3% of older patients (adjusted OR [aOR] 1.30, 95% CI 1.21 to 1.40), without evidence that age-related differences varied by sex (interaction p-value 0.25). Odds ratios of achieving target door-to-CT times and door-to-needle (DTN) times, and outcomes of rtPA-treated patients, are shown in the Table. Conclusions: Young acute ischemic stroke patients did not receive rt-PA treatment at lower rates than older patients. Outcomes were better and the rate of symptomatic intracranial hemorrhage was lower in the young patients. However, younger patients had significantly longer door-to-CT and DTN times, providing an opportunity to improve the care of these patients.

scholarly journals Intravenous Tissue-Type Plasminogen Activator in Acute Ischemic Stroke Patients With History of Stroke Plus Diabetes Mellitus

Stroke ◽  
2019 ◽  
Vol 50 (6) ◽  
pp. 1497-1503 ◽  
Author(s):  
Matthew E. Ehrlich ◽  
Li Liang ◽  
Haolin Xu ◽  
Andrzej S. Kosinski ◽  
Adrian F. Hernandez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Stroke Patients ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
History Of

scholarly journals Emergency Medicine Physicians Accurately Select Acute Stroke Patients for Tissue-Type Plasminogen Activator Treatment Using a Checklist

Stroke ◽  
2020 ◽  
Vol 51 (2) ◽  
pp. 663-665
Author(s):  
Ketevan Berekashvili ◽  
Alicia M. Zha ◽  
Mohammed Abdel-Al ◽  
Xu Zhang ◽  
Jazba H. Soomro ◽  
...  
Keyword(s):  
Emergency Medicine ◽  
Acute Stroke ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Stroke Patients ◽  
Tissue Type Plasminogen Activator ◽  
Stroke Mimics ◽  
Type Plasminogen Activator ◽  
Emergency Medicine Physician ◽  
Medicine Physician

Background and Purpose— There is uncertainty among many emergency medicine physicians about the decision to give intravenous tPA (tissue-type plasminogen activator), which limits its use. A checklist approach has been suggested as a solution. We compared agreement on tPA treatment in suspected acute ischemic stroke patients between emergency medicine residents (EMRs) using a checklist and vascular neurology fellows (VNFs). Methods— Every suspected acute stroke patient brought to our comprehensive stroke center emergency room within 4.5 hours from symptom onset was prospectively evaluated simultaneously and independently by VNFs and EMRs. The latter used a tPA screening checklist, which included guideline exclusion criteria to help with their treatment decision. Agreement was determined using kappa (k) statistics. Results— Over 6 months, 60 patients were enrolled; 10% large vessel atherosclerosis, 18% cardioembolism, 12% small vessel, 12% cryptogenic, and 47% mimic. Forty-two percent were deemed tPA eligible by the EMR, 30% by the VNF, and 37% by the vascular neurology faculty. There were no complications in any tPA-treated patients. Agreement was substantial between EMR and VNF (κ=0.68 [95% CI, 0.49–0.87]) and between EMR and vascular neurology faculty (κ=0.69 [95% CI, 0.50–0.87]). Stroke mimics were the main cause of disagreement between EMR and VNF (κ=0.24 [95% CI, −0.15 to 0.63]) and between EMR and vascular neurology faculty (κ=0.35 [95% CI, −0.08 to 0.78]). Conclusions— Our data suggest that with the aid of a checklist, EMRs can accurately treat stroke patients with tPA. Areas for improvement include recognition of stroke mimics. Further studies are warranted to evaluate checklist-enhanced tPA treatment to allay emergency medicine physician uncertainty and expand the use of tPA.

DWI Lesion Characteristics As A Predictor For Outcome In Acute Stroke Patients Treated By IV-tPA

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
H Aref ◽  
S Farag ◽  
S Helmy ◽  
H Mahmoud
Keyword(s):  
Ischemic Stroke ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
P Value ◽  
Stroke Patients ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Iv Tpa

Abstract Background Thrombolysis with tissue-type plasminogen activator (IV-tPA) is a well-proved, widely used treatment in acute ischemic stroke patients, many predictors of functional outcome have been proposed as Age, vascular risk factors, initial clinical evaluation on admission using National institute of health stroke scale(NIHSS), functional state of patient(b.L) baseline before stroke and 3 months (3m) after stroke using modified Rankin stroke scale (MRS)and the most controversial Diffusion weighted image characteristics (volume, heterogeneity) Objective To evaluate DWI MRI characteristics (volume, heterogeneity) as a predictor for outcome in Acute stroke patients treated by IV-tPA Patients and Methods This study will be done on a sample of 100 acute ischemic stroke Egyptian patients receiving intra-venous tissue -type plasminogen activator presenting to Ain-Shams university hospitals Results Highly statistically significant (p-value &lt; 0.001) Positive correlation (r = 0.394) between volume (DWI) and MRS (3m) post discharge in studied patients, No statistically significant (pvalue &gt; 0.05) relation between heterogeneity and other studied parameters (MRS, NIHSS D & ADC values) in studied patients Conclusion DWI infarct volume is a predictor for outcome in acute ischemic stroke patients treated by tPA

scholarly journals Primary Thrombectomy in tPA (Tissue-Type Plasminogen Activator) Eligible Stroke Patients With Proximal Intracranial Occlusions

Stroke ◽  
2018 ◽  
Vol 49 (1) ◽  
pp. 265-269 ◽  
Author(s):  
Urs Fischer ◽  
Johannes Kaesmacher ◽  
Carlos A. Molina ◽  
Magdy H. Selim ◽  
Andrei V. Alexandrov ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Type ◽  
Stroke Patients ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

scholarly journals Role of the MMP9 Gene in Hemorrhagic Transformations After Tissue-Type Plasminogen Activator Treatment in Stroke Patients

Stroke ◽  
2012 ◽  
Vol 43 (5) ◽  
pp. 1398-1400 ◽  
Author(s):  
Israel Fernández-Cadenas ◽  
Alberto del Río-Espínola ◽  
Caty Carrera ◽  
Sophie Domingues-Montanari ◽  
Maite Mendióroz ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Type ◽  
Stroke Patients ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Mmp9 Gene
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