Safety of High Doses of Urokinase and Reteplase for Acute Ischemic Stroke

Misra, Vivek; Khoury, Ramy El; Arora, Rohan; Chen, P. R.; Suzuki, Shinichi; Harun, Nusrat; Gonzales, Nicole R.; Barreto, Andrew D; Grotta, James C.; Savitz, Sean I

doi:10.3174/ajnr.a2427

Cited by 10 publications

(5 citation statements)

References 19 publications

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“…In addition, the differences in the incidence of intracranial hemorrhage and fatality rates had no statistical significance within 90 days after treatment between these two groups. This is in accordance with the results obtained by Lindsberg and Misra et al [7,8]. Misra et al [8] have used large doses of urokinase and reteplase for arterial thrombolysis in treating acute cerebral infarction and demonstrated that the incidence of intracranial hemorrhage and fatality rate in patients with symptomatic intracranial hemorrhage were not associated with the doses of intra-arterial thrombolytic drugs, which indicates that the safety in the use of arterial thrombolysis was higher in the treatment of acute cerebral infraction.…”

Section: Introductionsupporting

confidence: 94%

“…Comparing the intra-arterial thrombolysis curative effect of reteplase to that of the first generation of thrombolytic drug, urokinase, Sugg et al have demonstrated that intra-arterial thrombolytic therapy with reteplase is inclined to have a higher blood vessel recanalization rate and intracranial hemorrhage risks, but the differences between the two treatments have no statistical significance [19]. The clinical test using large doses of reteplase and urokinase for intra-arterial thrombolysis carried out by Misra et al also demonstrated similar results [8]. Our results showed that, among the 25 cases of patients accepting reteplase intra-arterial therapy, there are 10 cases of patients with blood vessel recanalization, and no case of patients with intracranial hemorrhage.…”

Section: Discussionmentioning

confidence: 94%

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Efficacy and Safety Evaluation on Arterial Thrombolysis in Treating Acute Cerebral Infarction

Shen

Liu

et al. 2015

Cell Biochem Biophys

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The objective of this study was to evaluate the efficacy and safety of intra-arterial thrombolysis in treating acute cerebral infarction and further discuss the indications of acute cerebral infarction treatment, in order to enhance the therapeutic effects of arterial thrombolysis. The data of 164 patients with acute cerebral infarction who accepted intra-arterial thrombolysis treatment by using rt-PA or reteplase between 2009 and 2014 at the Department of Neurology of our hospital, were collected, including patients' medical history, characteristics of the onset procedure, intervals between onset and intra-arterial thrombolysis, bleeding or death, and the changing process of patient's main neurologic function after the treatment. The neurological functions including muscle strength, speech, and level of consciousness were chosen for evaluation. Through a review of cerebral angiography, we collected the digital subtraction angiography (DSA) morphological changes of blood vessels before and after arterial thrombolysis to evaluate whether those blood vessels had been reperfused. Thereafter, we analyzed and statistically processed above-mentioned data. The mean time of arterial thrombolysis was 5.7 h. DSA results were as follows: 22 patients had complete internal carotid artery (ICA) occlusion; 49 patients middle cerebral artery's (MCA's) Ml or M2 segment occlusion; 6 patients anterior cerebral artery (ACA) occlusion; 58 patients reperfusion after thrombolysis, and the recanalization rate was 76 %. Based on vertebral-basilar artery (VBA) system, 18 patients had complete occlusion, 11 patients had reperfusion after thrombolysis, and the recanalization rate was 61 %. A total of 63 patients had severe stenosis, and they had significantly improved after thrombolysis. The clinical symptoms of patients were improved: 79 out of 164 patients with paralysis had partially recovered their limb muscle strength after operation, while 33 patients had completely recovered, and there was no recovery at all of the muscle strength in 4 patients after operation. In total, 59 out of 63 patients with aphasia had improved their language function, while 19 patients with disturbance of consciousness turned for the better after arterial thrombolysis. Only one patient experienced the cerebral hemorrhage, and 14 cases had gingival bleeding, oral mucosa bleeding, and urethrorrhagia. The overall effective rates of intra-arterial thrombolysis in treating the acute cerebral infarction by reteplase had no significant differences compared to those by rt-PA, and there were no hemorrhagic complications. It is safe and effective if the arterial thrombolysis using reteplase is performed within a few hours after acute cerebral infarction onset because reteplase has a higher clinical efficacy and lower hemorrhagic transformation, which suggests that it may become a new feasible option for clinical arterial thrombolysis.

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Section: Introductionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 94%

Efficacy and Safety Evaluation on Arterial Thrombolysis in Treating Acute Cerebral Infarction

Shen

Liu

et al. 2015

Cell Biochem Biophys

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“…Despite increasing the risk of haemorrhage, uPA is widely used as the main thrombolytic drug for ischaemic stroke in several countries, due particularly to its low cost (Dong et al 2017;Kleindorfer et al 2017;Lee et al 2012;Misra et al 2011). However, at present there is insufficient evidence for the efficacy and the safety profile of this therapy, necessitating larger clinical trials to support or dismiss the application of uPA for ischaemic stroke.…”

Section: Future Directionsmentioning

confidence: 99%

“…Even so, a limited number of studies performed with uPA have reported marked improvements in recanalisation and neurological outcomes similar to those achieved with treatments with rtPA (Ogawa et al 2007;Wang et al 2017). Furthermore, as uPA is significantly cheaper than rtPA, it is widely used in developing countries as the mainstay thrombolytic agent for acute ischaemic stroke (Dong et al 2017;Lee et al 2012;Misra et al 2011). Therefore, further investigation is urgently needed to reveal the actual benefit and safety profile of uPA.…”

Section: Introductionmentioning

confidence: 99%

Urokinase Plasminogen Activator: A Potential Thrombolytic Agent for Ischaemic Stroke

Kadir

Bayraktutan

2019

Cell Mol Neurobiol

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Stroke continues to be one of the leading causes of mortality and morbidity worldwide.Restoration of cerebral blood flow by recombinant plasminogen activator (rtPA) with or without mechanical thrombectomy is considered the most effective therapy for rescuing brain tissue from ischaemic damage, but this requires advanced facilities and highly skilled professionals, entailing high costs, thus in resource-limited contexts urokinase plasminogen activator (uPA) is commonly used as an alternative. This literature review summarises the existing studies relating to the potential clinical application of uPA in ischaemic stroke patients.In translational studies of ischaemic stroke, uPA has been shown to promote nerve regeneration and reduce infarct volume and neurological deficits. Clinical trials employing uPA as a thrombolytic agent have replicated these favourable outcomes and reported consistent increases in recanalisation, functional improvement, and cerebral haemorrhage rates, similar to those observed with rtPA. Single-chain zymogen pro-urokinase (pro-uPA) and rtPA appear to be complementary and synergistic in their action, suggesting that their co-administration may improve the efficacy of thrombolysis without affecting the overall risk of haemorrhage. Large clinical trials examining the efficacy of uPA or the combination of pro-uPA and rtPA are desperately required to unravel whether either therapeutic approach may be a safe first-line treatment option for patients with ischaemic stroke. In light of the existing limited data, thrombolysis with uPA appears to be a potential alternative to rtPA-mediated reperfusive treatment due to its beneficial effects on the promotion of revascularisation and nerve regeneration.

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“…However, reteplase seems to cause a greater adenosine diphosphate-and thrombin-induced platelet aggregation and a greater glycoprotein IIb/IIIa expression compared to alteplase, which is theoretically a disadvantage (54). Recently, Misra et al (59) reported that high intra-arterial doses of reteplase proved to be safe when administered with or without mechanical thrombolysis in 197 patients with AIS, also undergoing a full-dose intravenous alteplase treatment.…”

Section: Newer Thrombolytic Agentsmentioning

confidence: 99%

Edaravone (Radicut), a free radical scavenger, is a potentially useful addition to thrombolytic therapy in patients with acute ischemic stroke

et al. 2012

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Safety of High Doses of Urokinase and Reteplase for Acute Ischemic Stroke

Cited by 10 publications

References 19 publications

Efficacy and Safety Evaluation on Arterial Thrombolysis in Treating Acute Cerebral Infarction

Efficacy and Safety Evaluation on Arterial Thrombolysis in Treating Acute Cerebral Infarction

Urokinase Plasminogen Activator: A Potential Thrombolytic Agent for Ischaemic Stroke

Edaravone (Radicut), a free radical scavenger, is a potentially useful addition to thrombolytic therapy in patients with acute ischemic stroke

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