Abstract TP254: Clot Dissolution Is Better With Ultrasound Assisted Thrombolysis For Fresh Clots With Higher Cholesterol Content

Background: Intravenous tissue plasminogen activator (IV-tPA) remains the only drug for arterial recanalization in acute ischemic stroke (AIS). Clot composition differs according to the stroke etiology- clot from heart being fresh and rich in fibrin while the clot from an ulcerated plaque is rich in cholesterol. These characteristics might influence the therapeutic response to tPA as well as ultrasound-enhanced thrombolysis. We evaluated the impact of cholesterol content and age of the clot on its dissolution with tPA and ultrasound in an in-vitro model. Methods: Clot was prepared by mixing horse blood with Calcium-chloride solution. Cholesterin was added to increase cholesterol level up to 100 mg/dL. Periodic serum replacement was used to ‘age’ the clot. The clots were exposed to continuous 2-MHZ diagnostic transcranial Doppler (TCD) ultrasound (acoustic intensity 340mW/cm2) during thromolysis with tPA (355 IU/ml). Efficiency of thrombolysis was calculated as the percentage of clot weight-loss after 60 minutes. Clot characteristics after lysis were evaluated with surface emission microscope (SEM). Results: Significant increase in the weight of clot occurred with its increasing age (from 2 to 10 hours, the clot-weight increased from 37.28±2.87mg to 51.56±5.34mg; p<0.005). Exposure to ultrasound and tPA resulted in significant reduction in the clot-weight at 1 hour (from 35.50±3.23% to 24.71±2.11%; p<0.005). Although, no significant differences were noted between clot-cholesterol levels and lysis with TCD or tPA alone, combination of these modalities induced significant lysis in clots with higher cholesterol levels (clot-weight reduced by 41.68±2.3%) as compared to clots with normal cholesterol (30.60±4.10%; p<0.005). SEM demonstrated thicker and denser fibrin network in aged clots while higher number of activated platelets were noted on the surface of cholesterol-rich clots. Conclusion: Ultrasound-assisted thrombolysis with tPA work better for fresh thrombi with higher cholesterol levels. Our findings provide insights into the differential recanalization rates in acute ischemic stroke of various etiologies

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In-Hospital Delays for Acute Stroke Treatment Delivery During the COVID-19 Pandemic

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2020.170 ◽

2020 ◽

pp. 1-7

Author(s):

Aristeidis H. Katsanos ◽

Danielle de Sa Boasquevisque ◽

Mustafa Ahmed Al-Qarni ◽

Mays Shawawrah ◽

Rhonda McNicoll-Whiteman ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Stroke Patients ◽

State Of Emergency ◽

Treatment Delivery ◽

Stroke Treatment ◽

Intravenous Tissue Plasminogen Activator ◽

Before And After ◽

The Impact ◽

Central South

ABSTRACT: Background: We investigated the impact of regionally imposed social and healthcare restrictions due to coronavirus disease 2019 (COVID-19) to the time metrics in the management of acute ischemic stroke patients admitted at the regional stroke referral site for Central South Ontario, Canada. Methods: We compared relevant time metrics between patients with acute ischemic stroke receiving intravenous tissue plasminogen activator (tPA) and/or endovascular thrombectomy (EVT) before and after the declared restrictions and state of emergency imposed in our region (March 17, 2020). Results: We identified a significant increase in the median door-to-CT times for patients receiving intravenous tPA (19 min, interquartile range (IQR): 14–27 min vs. 13 min, IQR: 9–17 min, p = 0.008) and/or EVT (20 min, IQR: 15–33 min vs. 11 min, IQR: 5–20 min, p = 0.035) after the start of social and healthcare restrictions in our region compared to the previous 12 months. For patients receiving intravenous tPA treatment, we also found a significant increase (p = 0.005) in the median door-to-needle time (61 min, IQR: 46–72 min vs. 37 min, IQR: 30–50 min). No delays in the time from symptom onset to hospital presentation were uncovered for patients receiving tPA and/or endovascular reperfusion treatments in the first 1.5 months after the establishment of regional and institutional restrictions due to the COVID-19 pandemic. Conclusion: We detected an increase in our institutional time to treatment metrics for acute ischemic stroke patients receiving tPA and/or endovascular reperfusion therapies, related to delays from hospital presentation to the acquisition of cranial CT imaging for both tPA- and EVT-treated patients, and an added delay to treatment with tPA.

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A new aspiration device equipped with a hydro-separator for acute ischemic stroke due to challenging soft and stiff clots

Interventional Neuroradiology ◽

10.1177/15910199211015060 ◽

2021 ◽

pp. 159101992110150

Author(s):

Naoki Kaneko ◽

Mahsa Ghovvati ◽

Yutaro Komuro ◽

Lea Guo ◽

Kasra Khatibi ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Stent Retriever ◽

Inverse Association ◽

Success Rates ◽

Endovascular Thrombectomy ◽

Vitro Model ◽

The Impact ◽

Continuous Suction

Objective Fragile soft clots and stiff clots remain challenging in the treatment of acute ischemic stroke. This study aims to investigate the impact of clot stiffness on the efficacy of thrombectomy devices and a new aspiration catheter with a hydro-separator. Methods The Neurostar aspiration catheter has a novel hydro-separator technology that macerates clots by a stream of saline inside the catheter. The Neurostar catheter and two commercially available devices, the SOFIA aspiration catheter and Solitaire stent retriever, were tested in this study. We evaluated the efficacy of each device on clots with various stiffness in a simple in vitro model. We also assessed single-pass recanalization performance in challenging situations with large erythrocyte-rich clots and fibrin-rich clots in a realistic vascular model. Results We observed an inverse association between the clot stiffness and recanalization rates. The aspiration catheter, SOFIA ingested soft clots but not moderately stiff clots. When removing soft clots with the stent retriever, fragmentation was observed, although relatively stiff clots were well-integrated and removed. The Neurostar ingested soft clots similar to the aspiration catheter, and also aspirated stiff clots by continuous suction with hydro-separator. In the experiments with challenging clots, the Neurostar led to significantly higher recanalization rates than the stent retriever and aspiration catheter. Conclusions The stiffness of the clots affected the efficacy of endovascular thrombectomy based on the type of device. The Neurostar catheter with hydro-separator resulted in better success rates than a commercially available aspiration catheter and stent retriever in this experimental model.

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Abstract 197: Time Dependency and Relationship to Reperfusion Grade in Acute Ischemic Stroke

Stroke ◽

10.1161/str.46.suppl_1.197 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Shyam Prabhakaran ◽

Alicia C Castonguay ◽

Rishi Gupta ◽

Chung-Huan Chung-Huan J. Sun ◽

Coleman Coleman Martin ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Strong Predictor ◽

Outcome Data ◽

Anterior Circulation ◽

Nihss Score ◽

Good Outcome ◽

The North ◽

Intravenous Tissue Plasminogen Activator ◽

The Impact

Background: Time to reperfusion following endovascular treatment (ET) strongly predicts outcomes after acute ischemic stroke (AIS). However, the impact of time may vary depending on the grade of reperfusion. We sought to assess time-outcome relationship within grades of reperfusion in the North American Solitaire Acute Stroke (NASA) registry. Methods: The investigator-initiated NASA registry recruited 24 clinical sites within North America to submit demographic, clinical, site-adjudicated angiographic, and clinical outcome data on consecutive patients treated with the Solitaire Flow Restoration device. We identified patients treated with anterior circulation ischemic stroke treated within 8 hours. The modified Thrombolysis in Cerebral Ischemia (TICI) was used wherein TICI 2 was divided in TICI 2a (< 50% reperfusion) and TICI 2b (> 50% reperfusion). We assessed the impact of time to reperfusion (onset to procedure completion time) on good outcome (modified Rankin Scale 0-2 at 3 months) in those who achieved at least TICI 2a reperfusion, independent of other relevant covariates using logistic regression analysis. We further assessed this relationship within strata of reperfusion grade. Results: Among 265 eligible patients, 209 (78.9%) had complete data (mean age 68.4 years, median NIHSS score 18). Reperfusion grade was as follows: TICI 3: 35.4%; TICI 2b: 39.7%, TICI 2a: 14.8%; TICI 0-1: 10.0%. Independent predictors of outcome at 3 months among those achieving TICI 2-3 reperfusion were: initial NIHSS score, intravenous tissue plasminogen activator use, symptomatic hemorrhage, and time to reperfusion. For each 30 minutes, the adjusted OR for time to reperfusion was 0.874 (95% CI 0.797-958). There was a significant interaction between final TICI grade and 30-minute time to reperfusion intervals (P=0.001) such that the effect of time was strongest in TICI 2a patients. Conclusions: Time to reperfusion is a strong predictor of outcome following ET for AIS with 13% decreased odds of good outcome per 30-minute delay in achieving TICI 2-3 reperfusion. However, the effect varied by TICI grade such that its greatest effect was in those achieving TICI 2a reperfusion.

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Symptomatic Intracerebral Hemorrhage Among Eligible Warfarin-Treated Patients Receiving Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke

Yearbook of Neurology and Neurosurgery ◽

10.1016/j.yneu.2011.03.014 ◽

2011 ◽

Vol 2011 ◽

pp. 10-11

Author(s):

A.A. Rabinstein

Keyword(s):

Ischemic Stroke ◽

Intracerebral Hemorrhage ◽

Acute Ischemic Stroke ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Intravenous Tissue Plasminogen Activator ◽

Symptomatic Intracerebral Hemorrhage ◽

Tissue Plasminogen

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Faculty Opinions recommendation of Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718021390.793479381 ◽

2013 ◽

Author(s):

Patrick Ray

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Time To Treatment ◽

Intravenous Tissue Plasminogen Activator ◽

Tissue Plasminogen

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The impact of antihypertensive use in the treatment of acute ischemic stroke in patients receiving alteplase

The American Journal of Emergency Medicine ◽

10.1016/j.ajem.2021.07.037 ◽

2021 ◽

Author(s):

Megan A. Rech ◽

Elisabeth Donahey ◽

Joshua M. DeMott ◽

Laura L. Coles ◽

Gary D. Peksa

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

The Impact

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Incorporation of α2-Plasmin Inhibitor into Fibrin Clots and Its Association with the Clinical Outcome of Acute Ischemic Stroke Patients

Biomolecules ◽

10.3390/biom11030347 ◽

2021 ◽

Vol 11 (3) ◽

pp. 347

Author(s):

Zsuzsa Bagoly ◽

Barbara Baráth ◽

Rita Orbán-Kálmándi ◽

István Szegedi ◽

Réka Bogáti ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Intravenous Thrombolysis ◽

Fibrin Clot ◽

Clot Lysis ◽

Stroke Patients ◽

Plasmin Inhibitor ◽

Fibrin Clots

Cross-linking of α2-plasmin inhibitor (α2-PI) to fibrin by activated factor XIII (FXIIIa) is essential for the inhibition of fibrinolysis. Little is known about the factors modifying α2-PI incorporation into the fibrin clot and whether the extent of incorporation has clinical consequences. Herein we calculated the extent of α2-PI incorporation by measuring α2-PI antigen levels from plasma and serum obtained after clotting the plasma by thrombin and Ca2+. The modifying effect of FXIII was studied by spiking of FXIII-A-deficient plasma with purified plasma FXIII. Fibrinogen, FXIII, α2-PI incorporation, in vitro clot-lysis, soluble fibroblast activation protein and α2-PI p.Arg6Trp polymorphism were measured from samples of 57 acute ischemic stroke patients obtained before thrombolysis and of 26 healthy controls. Increasing FXIII levels even at levels above the upper limit of normal increased α2-PI incorporation into the fibrin clot. α2-PI incorporation of controls and patients with good outcomes did not differ significantly (49.4 ± 4.6% vs. 47.4 ± 6.7%, p = 1.000), however it was significantly lower in patients suffering post-lysis intracranial hemorrhage (37.3 ± 14.0%, p = 0.004). In conclusion, increased FXIII levels resulted in elevated incorporation of α2-PI into fibrin clots. In stroke patients undergoing intravenous thrombolysis treatment, α2-PI incorporation shows an association with the outcome of therapy, particularly with thrombolysis-associated intracranial hemorrhage.

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Eosinophil-to-monocyte ratio is a potential biomarker in the prediction of functional outcome among patients with acute ischemic stroke

BMC Neuroscience ◽

10.1186/s12868-021-00610-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Shuhong Yu ◽

Yi Luo ◽

Tan Zhang ◽

Chenrong Huang ◽

Yu Fu ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Odds Ratio ◽

Poor Outcome ◽

Net Reclassification Improvement ◽

Potential Biomarker ◽

The Impact ◽

The Relationship ◽

Integrated Discrimination Improvement

Abstract Background It has been shown that eosinophils are decreased and monocytes are elevated in patients with acute ischemic stroke (AIS), but the impact of eosinophil-to-monocyte ratio (EMR) on clinical outcomes among AIS patients remains unclear. We aimed to determine the relationship between EMR on admission and 3-month poor functional outcome in AIS patients. Methods A total of 521 consecutive patients admitted to our hospital within 24 h after onset of AIS were prospectively enrolled and categorized in terms of quartiles of EMR on admission between August 2016 and September 2018. The endpoint was the poor outcome defined as modified Rankin Scale score of 3 to 6 at month 3 after admission. Results As EMR decreased, the risk of poor outcome increased (p < 0.001). Logistic regression analysis revealed that EMR was independently associated with poor outcome after adjusting potential confounders (odds ratio, 0.09; 95% CI 0.03–0.34; p = 0.0003), which is consistent with the result of EMR (quartile) as a categorical variable (odds ratio, 0.23; 95% CI 0.10–0.52; ptrend < 0.0001). A non-linear relationship was detected between EMR and poor outcome, whose point was 0.28. Subgroup analyses further confirmed these associations. The addition of EMR to conventional risk factors improved the predictive power for poor outcome (net reclassification improvement: 2.61%, p = 0.382; integrated discrimination improvement: 2.41%, p < 0.001). Conclusions EMR on admission was independently correlated with poor outcome in AIS patients, suggesting that EMR may be a potential prognostic biomarker for AIS.

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