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Thrombolytic, stroke, extend window

Ahmet Yigit Goktay, Cagin Senturk
Deep venous thrombosis (DVT) is a common disorder with a significant mortality rate. Successful endovascular treatment of acute DVT is most likely to be achieved in patients with recently formed thrombus, (<10-14 days) with acute iliofemoral DVT. Endovascular treatment options include: Catheter-directed thrombolysis (CDT), pharmacomechanical catheter-directed thrombolysis (PCDT), percutaneous aspiration thrombectomy (PAT), vena cava filter protection, venous balloon dilatation and venous stent implantation...
September 24, 2016: Advances in Experimental Medicine and Biology
Han-Sen Chen, Su-Hua Qi, Jian-Gang Shen
Tissue plasminogen activator (t-PA) is the only FDA approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA's therapeutic time window. However, therapies modulating single target seems not satisfying, and a multi-target strategy is warranted to resolve such complex disease...
June 19, 2016: Current Neuropharmacology
Tobias A Mattei, Azeem A Rehman, Carlos R Goulart, Marília G Sória, Vanessa Rizelio, Murilo S Meneses
BACKGROUND: Although intravenous thrombolysis is the Food and Drug Administration-approved treatment for acute ischemic stroke (AIS) within 3 h, combined intravenous and intra-arterial thrombolysis with endovascular techniques may be able to extend this traditional time window. CASE DESCRIPTION: We present the clinical evolution of a 45-year-old male presenting with acute left hemiparesis. Magnetic resonance imaging revealed a small diffusion restriction at the right basal ganglia with perfusion compromise in the entire right middle cerebral artery (MCA) territory...
2016: Surgical Neurology International
Han-Sen Chen, Su-Hua Qi, Jian-Gang Shen
Tissue plasminogen activator (t-PA) is the only FDA approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA's therapeutic time window. However, therapies modulating single target seems not satisfying, and a multi-target strategy is warranted to resolve such complex disease...
December 7, 2015: Current Neuropharmacology
Teruyuki Hirano
Currently, the indication for thrombolytic therapy using intravenous recombinant tissue plasminogen activator (rt-PA) is restricted strictly to patients with acute ischemic stroke within 4.5 h of onset. The effect of rt-PA declines over time; therefore, we need to minimize the time delay while generating imaging information. The use of cerebral blood flow imaging is not recommended within this time window. Conversely, the balance of efficacy and the risk of bleeding complications differ among patients > 4...
2015: Neurologia Medico-chirurgica
Zhenjun Tan, Brandon P Lucke-Wold, Aric F Logsdon, Ryan C Turner, Cong Tan, Xinlan Li, Jarin Hongpaison, Daniel L Alkon, James W Simpkins, Charles L Rosen, Jason D Huber
Blood-brain barrier (BBB) disruption and hemorrhagic transformation (HT) following ischemic/reperfusion injury contributes to post-stroke morbidity and mortality. Bryostatin, a potent protein kinase C (PKC) modulator, has shown promise in treating neurological injury. In the present study, we tested the hypothesis that administration of bryostatin would reduce BBB disruption and HT following acute ischemic stroke; thus, prolonging the time window for administering recombinant tissue plasminogen activator (r-tPA)...
October 5, 2015: European Journal of Pharmacology
Randolph S Marshall
IMPORTANCE: Intravenous recombinant tissue plasminogen activator (alteplase) was approved by the US Food and Drug Administration in 1996 for the treatment of acute ischemic stroke. Nearly 20 years later, it remains the only approved treatment, despite limitations in both efficacy and safety. With a growing capacity for stroke treatment worldwide, physicians need to understand where we have come from and what the future of stroke treatment might be. OBJECTIVE: To present a historical prospective as well as current trends in thrombolytic therapy, focusing on characteristics of drugs that have worked and clinical trials that are moving the field forward...
August 2015: JAMA Neurology
Zhenjun Tan, Xinlan Li, Ryan C Turner, Aric F Logsdon, Brandon Lucke-Wold, Kenneth DiPasquale, Soon Soeg Jeong, Ridong Chen, Jason D Huber, Charles L Rosen
Recombinant tissue plasminogen activator (r-tPA) is the only FDA-approved drug treatment for ischemic stroke and must be used within 4.5h. Thrombolytic treatment with r-tPA has deleterious effects on the neurovascular unit that substantially increases the risk of intracerebral hemorrhage if administered too late. These therapeutic shortcomings necessitate additional investigation into agents that can extend the therapeutic window for safe use of thrombolytics. In this study, combination of r-tPA and APT102, a novel form of human apyrase/ADPase, was investigated in a clinically-relevant aged-female rat embolic ischemic stroke model...
September 5, 2014: European Journal of Pharmacology
Marie Dagonnier, David W Howells, Geoffrey A Donnan, Helen M Dewey
To increase the percentage of acute stroke patients benefiting from thrombolysis, the utility of expanding the time window of treatment beyond 4.5 hours after stroke onset needs to be investigated. We aimed to identify the target population and the challenges of recruitment of patients for the time window beyond 4.5 hours. Extending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND), a multicentre randomised controlled trial testing the efficacy of thrombolytic therapy in patients with clinically significant ischaemic penumbra between 4...
July 2014: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Andrew Bivard, Longting Lin, Mark W Parsonsb
The cornerstone of acute ischemic stroke treatment relies on rapid clearance of an offending thrombus in the cerebrovascular system. There are various drugs and different methods of assessment to select patients more likely to respond to treatment. Current clinical guidelines recommend the administration of intravenous alteplase (following a brain noncontract CT to exclude hemorrhage) within 4.5 hours of stroke onset. Because of the short therapeutic time window, the risk of hemorrhage, and relatively limited efficacy of alteplase for large clot burden, research is ongoing to find more effective and safer reperfusion therapy, as well as focussing on refinement of patient selection for acute reperfusion treatment...
May 2013: Journal of Stroke
Weihua Guan, Yumei Zhao, Chao Xu
Combination treatment may target different pathophysiological events following cerebral ischemia thus enhancing the efficacy of treatment in thromboembolic stroke. Taurine confers a neuroprotective effect in the mechanical stroke model. This effect has not been assessed in an embolic stroke model. Here, we sought to evaluate the neuroprotective effect of taurine alone and in combination with thrombolytic therapy to investigate whether combined administration would extend the therapeutic time window without increasing the hemorrhagic transformation in a rat embolic stroke model...
March 2011: Translational Stroke Research
Adriana Sofia Ploneda Perilla, Michael J Schneck
This article reviews some of the current literature in support or against extension of the intravenous tissue plasminogen activator window, use of intra-arterial therapy or devices, as well alternative pharmacologic therapies that may extend the window for treatment of patients with acute ischemic stroke, with consideration of the relative risk of thrombolytic complications, factors for worse outcomes, and unclear stroke onset, as seen in patients with wake-up stroke. The issue of newer concomitant antithrombotic therapies as they affect the decision for acute ischemic stroke thrombolytic therapy is also explored...
August 2013: Neurologic Clinics
Muhammad Faisal Wadiwala, Ayeesha Kamran Kamal
No abstract text is available yet for this article.
August 2012: JPMA. the Journal of the Pakistan Medical Association
Kazunori Toyoda
Intravenous thrombolysis using alteplase was approved for clinical use for acute ischemic stroke treatment in Japan in 2005, on the basis of the results of a domestic clinical trial, Japan Alteplase Clinical Trial. This therapeutic strategy has become the standard strategy during the following 8 years. However, this therapy still has room for improvement. One of the important drawbacks of intravenous thrombolysis is the limited therapeutic time window. On the basis of the results of the European Cooperative Acute Stroke Study III and the pooled analysis, the current time window is within 4...
July 2013: Brain and Nerve, Shinkei Kenkyū No Shinpo
Qingke Bai, Zhenguo Zhao, Haijing Sui, Xiuhai Xie, Juan Chen, Juan Yang, Li Zhang
OBJECTIVE: Fast magnetic resonance imaging (MRI) and susceptibility-weighted imaging (SWI) methods may provide more accurate detection of the highly variant time window for successful intravenous (IV) thrombolytic drug treatment (averaging 3 hours) for cerebral microbleeds (CMBs) in acute stroke patients. METHODS: This prospective study applies fast MRI and SWI for examination of 279 prescreened ischemic stroke patients within 12 hours of stroke onset. One hundred and sixty-two (58...
July 2013: Neurological Research
Sameer Bansal, Kiranpal S Sangha, Pooja Khatri
Acute ischemic stroke (AIS) is the fourth leading cause of death and the leading cause of adult disability in the USA. AIS most commonly occurs when a blood vessel is obstructed leading to irreversible brain injury and subsequent focal neurologic deficits. Drug treatment of AIS involves intravenous thrombolysis with alteplase (recombinant tissue plasminogen activator [rtPA]). Intravenous alteplase promotes thrombolysis by hydrolyzing plasminogen to form the proteolytic enzyme plasmin. Plasmin targets the blood clot with limited systemic thrombolytic effects...
February 2013: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
Thompson Robinson, Zahid Zaheer, Amit K Mistri
Stroke is a major cause of mortality and morbidity, and thrombolysis has served as a catalyst for major changes in the management of acute ischaemic stroke. Intravenous alteplase (recombinant tissue plasminogen activator) is the only approved thrombolytic agent at present indicated for acute ischaemic stoke. While the licensed time window extends to 3h from symptom onset, recent data suggest that the trial window can be extended up to 4.5 h with overall benefit. Nonetheless, 'time is brain' and every effort must be made to reduce the time delay to thrombolysis...
March 2011: Therapeutic Advances in Chronic Disease
Xiao-Ling Liao, Chun-Xue Wang, Yi-Long Wang, Chun-Juan Wang, Xing-Quan Zhao, Li-Qun Zhang, Li-Ping Liu, Yue-Song Pan, Yong-Jun Wang
BACKGROUND AND PURPOSE: The European Cooperative Acute Stroke Study (ECASS) III showed that intravenous recombinant tissue plasminogen activator (rtPA) administered in the 3 to 4.5 h after symptom onset significantly improved clinical outcomes in patients with acute ischemic stroke (AIS). But little is known regarding the safety and efficacy of intravenous rtPA treatment within this extended time window in Chinese patients with AIS. METHODS AND RESULTS: Data were collected from the Thrombolysis Implementation and Monitor of acute ischemic Stroke in China (TIMS-China)...
January 2013: CNS Neuroscience & Therapeutics
Pablo García-Bermejo, Ana I Calleja, Santiago Pérez-Fernández, Elisa Cortijo, José M del Monte, Miguel García-Porrero, M Fe Muñoz, Rosario Fernández-Herranz, Juan F Arenillas
BACKGROUND: Extending the therapeutic window of intravenous thrombolysis for acute ischemic stroke beyond the established 4.5-hour limit is of critical importance in order to increase the proportion of thrombolysed stroke patients. In this setting, the capacity of MRI to select acute stroke patients for reperfusion therapies in delayed time windows has been and is being tested in clinical trials. However, whether the more available and cost-effective perfusion computed tomography (PCT) may be useful to select candidates for delayed intravenous thrombolysis remains largely unexplored...
2012: Cerebrovascular Diseases
M Ishiguro, K Kawasaki, Y Suzuki, F Ishizuka, K Mishiro, Y Egashira, I Ikegaki, K Tsuruma, M Shimazawa, S Yoshimura, T Iwama, H Hara
Thrombolysis with tissue plasminogen activator (tPA) is the only FDA-approved therapy for acute ischemic stroke. However, hemorrhagic transformation, neurotoxicity, and a short treatment time window comprise major limitations for thrombolytic therapy. The purpose of the present study was to investigate whether fasudil, a Rho kinase (ROCK) inhibitor, would prevent tPA-associated hemorrhagic transformation and extend the reperfusion window in an experimental stroke model in mice. Mice subjected to 6-h middle cerebral artery occlusion were treated with delayed tPA alone, with combined tPA plus fasudil, or with a vehicle...
September 18, 2012: Neuroscience
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