scholarly journals Effects of Tissue Plasminogen Activator and Annexin A2 Combination Therapy on Long-Term Neurological Outcomes of Rat Focal Embolic Stroke

Stroke ◽  
2014 ◽  
Vol 45 (2) ◽  
pp. 619-622 ◽  
Author(s):  
Xiaoshu Wang ◽  
Xiang Fan ◽  
Zhanyang Yu ◽  
Zhengbu Liao ◽  
Jianhua Zhao ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Annexin A2 ◽  
Embolic Stroke ◽  
Neurological Outcomes ◽  
Tissue Plasminogen

Abstract TP74: Early Administration of Tissue-plasminogen Activator Improves the Long-term Clinical Outcome at 5 Years After Onset

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Junya Aoki ◽  
Kazumi Kimura ◽  
Yuki Sakamoto
Keyword(s):  
Regression Analysis ◽  
Confidence Interval ◽  
Plasminogen Activator ◽  
Clinical Outcomes ◽  
Tissue Plasminogen Activator ◽  
Odds Ratio ◽  
Univariate Analysis ◽  
Favorable Outcome ◽  
Tissue Plasminogen

Introduction & Hypothesis: Data on long-term outcomes after tissue-plasminogen activator (tPA) therapy are limited. We evaluated the rate of favorable outcomes and mortality at 5 years after tPA therapy and investigated factors related to long-term clinical outcomes. Methods: Telephone interviews were used to assess the to the the modified Rankin Scale (mRS) scores at 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years after tPA therapy after written informed consent was obtained. When a telephone interview was not successfully accomplished, an interview letter was sent as an alternative method. Favorable outcome was defined as mRS 0-2, and unfavorable outcome was as mRS 3-6. Multivariate logistic regression analysis was conducted to investigate factors associated with favorable outcomes and mortality at 5 years after tPA therapy. Results: From 2005 to 2013, 256 (median age, 77 [interquartile range, 68-84] years; 157 [61%] males) patients were enrolled. The onset-to-treatment time (OTT) was 153 (120-176) minutes. At 3 months after tPA therapy, the median mRS score was assessed as 3 (1-5). Kaplan-Meier curve showed that favorable outcomes after 5 years after tPA therapy occurred in 45% patients and that the mortality rate was 40%. Univariate analysis showed that OTT was 123 (107-172) minutes in patients with favorable outcomes and 155 (124-172) minutes in patients with non-favorable outcomes (p=0.046). In addition, OTT was 157 (133-172) minutes in the death group and 123 (106-169) minutes in the survival group (p=0.001). Multivariate regression analysis indicated that OTT was an independent factor related to favorable outcomes (odds ratio 0.97, 95% confidence interval 0.95-0.99, p=0.008) and mortality (odds ratio 1.04, 95% confidence interval 1.02-1.06, p=0.001). Receiver operating characteristic curve analysis showed that OTT ≥ 136 minutes was the optimal cut-off value to predict favorable outcome at 5 years after tPA therapy, with a sensitivity of 0.67, a specificity of 0.70, and an area under curve (AUC) of 0.662 (p=0.016), and that to predict death within 5 years after tPA therapy, with a sensitivity of 0.70, a specificity of 0.66, and an AUC of 0.679 (p=0.001). Conclusion: Early tPA administration can improves long-term clinical outcomes.

Abstract T P66: Safety and Effectiveness of Intravenous Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke Patients on Aspirin and Clopidogrel

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Mushtaq H Qureshi ◽  
Shayaan M Khan ◽  
Nauman Jahangir ◽  
Ahmed A Malik ◽  
Melissa Freese ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Combination Therapy ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Recombinant Tissue Plasminogen Activator ◽  
Favorable Outcome ◽  
Stroke Patients ◽  
Neurological Improvement ◽  
Tissue Plasminogen

Background: The number of acute ischemic stroke patients who are on both aspirin and clopidogrel treatment at time of acute ischemic event is increasing. There is limited data regarding the safety and efficacy of intravenous recombinant tissue plasminogen activator (rt-PA) treatment in such patients. Methods: We reviewed the medical records and imaging data of consecutive patients with acute ischemic stroke who received IV rt-PA within 4.5 hours of symptom onset. We stratified the patients based on active regular use of antiplatelet medications: monotherapy (aspirin or clopidogrel), combination therapy (aspirin and clopidogrel), and no therapy and compared the rates of symptomatic intracerebral hemorrhage (ICH), neurological improvement (≥4 points in National Institutes of Health Stroke Scale [NIHSS], and favorable outcome (modified Rankin scale [mRS] 0-1) at discharge between the three groups. Results: A total of 88 acute ischemic stroke patients (mean age±SD; 69.88 ±15) were treated with IV rt-PA within the study duration. Of the 88 patients 45 (50.6%), 37 (41.6%), and 52 (58.4) were on monotherapy, combination therapy, or no therapy at time of presentation. The proportion of patients who developed symptomatic ICHs were similar (p=0.8) in monotherapy, combination therapy, and no therapy groups (3.3%, 0.0%, and 4.1%, respectively). The rates of neurological improvement were greater in patients on monotherapy (20%) (p=0.03) followed by combination therapy (11.1%), and no therapy groups (2.0%). There was no significant reduction in the rate of favorable outcome at discharge among patients on combination treatment compared with no treatment (odds ratio 0.8 , 95% confidence interval 0.4-1.8 ) after adjusting for age and initial NIHSS score strata (<10, 10-19, and ≥20). Conclusions: Compared with patients on no antiplatelet treatment, acute ischemic stroke patients who are actively using aspirin and clopidogrel appear to have similar risks and benefits with IV rt-PA treatment.

Abstract 168: Outcomes of Intra-Arterial Tissue Plasminogen Activator Rescue Therapy During Stroke Thrombectomy-Insights From the STAR Collaboration

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Eyad Almallouhi ◽  
Sami Al kasab ◽  
Ali Alawieh ◽  
Reda M Chalhoub ◽  
Mohammad Anadani ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Functional Outcomes ◽  
Mechanical Thrombectomy ◽  
Rescue Therapy ◽  
Adjunctive Treatment ◽  
Control Group ◽  
Arterial Tissue ◽  
Tissue Plasminogen

Introduction: Intra-arterial tissue plasminogen activator (IA-tPA) can be used as rescue therapy during mechanical thrombectomy for stroke patients, mostly in the setting of distal occlusion. The outcomes of IA-tPA has not been assessed in large-scale multi-center studies yet. Methods: We used data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which included prospectively maintained databases of 11 thrombectomy-capable stroke centers in the US, Europe, and Asia. We compared the baseline characteristics, procedural metrics, rate of symptomatic intracranial hemorrhage (sICH), and long-term functional outcomes between thrombectomy patients who received rescue IA-tPA and a control group of thrombectomy patients with matched age, National Institute of Health stroke scale (NIHSS) on presentation, location of occlusion and IV-tPA receipt. Results: A total of 2827 thrombectomy patients were included in the STAR registry. Out of those, 205 patients received IA-tPA. We matched 191 patients from the IA-tPA group with a control group of 191 patients (table 1). No difference was seen in age, sex, race, vascular risk factors, or Alberta Stroke Program Early CT (ASPECT) score between both groups. In addition, procedural metrics, including onset to groin time, the procedure duration, and rate of successful recanalization (modified Thrombolysis in Cerebral Infarction score≥2b) were similar. Finally, similar outcomes were noted in both groups, including the rate of sICH and good 90-day functional outcome (modified Rankin scale≤2). Conclusion: The use of IA-tPA as an adjunctive treatment to mechanical thrombectomy was safe but did not result in a higher rate of successful recanalization or good long-term functional outcomes.

Abstract WP105: Tissue Plasminogen Activator (tPA) is Essential for Functional Recovery After Stroke by Promoting Axonal Outgrowth

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Shubei Ma
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Functional Recovery ◽  
Stroke Recovery ◽  
White Matter Integrity ◽  
Blue Staining ◽  
Tissue Plasminogen

Objectives: Stroke is the leading cause of long term neurological disability with limited therapeutic options. Human recombinant tissue plasminogen activator (tPA) is currently the only FDA approved drug for the thrombolytic treatment of ischemic stroke. Emerging evidence suggests that the effects of tPA in ischemic brain may extend beyond its thrombolytic activity. In this study, we investigated the role of tPA in long term stroke recovery. Methods: Cortical infarct was induced by distal middle cerebral artery occlusion (dMCAO) in tPA knockout (KO) and wild type (WT) mice. Sensorimotor functions were evaluated at 3-35 days after dMCAO. White matter integrity was assessed by luxol fast blue staining, immunohistochemistry for SMI-32, and diffusion tensor imaging (DTI). The neuronal tracer biotinylated dextran amine (BDA) was used to label the corticorubral tract and the corticospinal tract. For rescue experiment, tPA (2mg/kg) was delivered intranasally to tPA KO mice once a day for 14 days starting 6h after dMCAO. Results: Infarct volume was comparable between tPA KO and WT mice after dMCAO. Sensorimotor deficits after dMCAO were exacerbated in tPA KO mice than WT mice. tPA KO mice also showed more severe demyelination in post-stroke white matter and reduced axonal sprouting at 35 days after dMCAO compared to WT mice. DTI studies revealed deteriorated white matter integrity in tPA KO mice, as manifested by decreased fractional anisotropy. Intranasal delivery of tPA after dMCAO rescued the neurological phenotype shown by tPA KO mice. Conclusion: Endogenous tPA promotes white matter integrity and is essential for functional recovery after ischemic stroke. tPA may be a novel neurorestorative therapy for stroke recovery.

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