No exacerbation of perihematomal edema with intraclot urokinase in patients with spontaneous intracerebral hemorrhage

Lian, Lifei; Xu, Feng; Hu, Qi; Liang, Qiansheng; Zhu, Wenhao; Hj, Kang; Liu, Xiaoyan; Tang, Zhouping; Zhu, Suiqiang

doi:10.1007/s00701-014-2130-9

Cited by 9 publications

(8 citation statements)

References 28 publications

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“…Furthermore, an increasing number of clinical studies have proposed that uPA carries a high fibrinolytic potential without excitotoxicity, thus representing a novel, promising candidate for fibrinolytic therapy for ICH. 5,8,23,38 In agreement with the above publications, our results also revealed the greater efficacy of uPA, compared with tPA, in ameliorating PHE and motor function after ICH.…”

Section: Discussionsupporting

confidence: 92%

“…Furthermore, according to the proportion between hematoma size and drug dosage, the established dose of tPA and uPA are equivalent to the dosage in ICH patients. 8,23,26 To avoid additional injury to the normal perihematomal brain tissue during intraclot drainage, we used fibrinolytic injection alone rather than fibrinolytic injection with intraclot drainage. The bur hole was sealed with bone wax, and the skin incision was closed with sutures after the needle was removed.…”

Section: Experimental Groups and Fibrinolytic Therapymentioning

confidence: 99%

“…13,14 A growing number of clinical research studies have reported that uPA not only increases the rate of clot resolution but also improves patient outcome in ICH fibrinolysis. 5,8,23,38 Nevertheless, no preclinical or clinical studies have evaluated the differen-tial effect of these 2 agents for fibrinolytic therapy following ICH. We hypothesized that uPA could provide greater benefits than tPA when used for ICH fibrinolysis.…”

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confidence: 99%

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Urokinase, a promising candidate for fibrinolytic therapy for intracerebral hemorrhage

Tan

Chen

Niu

et al. 2017

JNS

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OBJECTIVE Intracerebral hemorrhage (ICH) is associated with a high rate of mortality and severe disability, while fibrinolysis for ICH evacuation is a possible treatment. However, reported adverse effects can counteract the benefits of fibrinolysis and limit the use of tissue-type plasminogen activator (tPA). Identifying appropriate fibrinolytics is still needed. Therefore, the authors here compared the use of urokinase-type plasminogen activator (uPA), an alternate thrombolytic, with that of tPA in a preclinical study. METHODS Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats by injecting autologous blood into the caudate, followed by intraclot fibrinolysis without drainage. Rats were randomized to receive uPA, tPA, or saline within the clot. Hematoma and perihematomal edema, brain water content, Evans blue fluorescence and neurological scores, matrix metalloproteinases (MMPs), MMP mRNA, blood-brain barrier (BBB) tight junction proteins, and nuclear factor-κB (NF-κB) activation were measured to evaluate the effects of these 2 drugs in ICH. RESULTS In comparison with tPA, uPA better ameliorated brain edema and promoted an improved outcome after ICH. In addition, uPA therapy more effectively upregulated BBB tight junction protein expression, which was partly attributed to the different effects of uPA and tPA on the regulation of MMPs and its related mRNA expression following ICH. CONCLUSIONS This study provided evidence supporting the use of uPA for fibrinolytic therapy after ICH. Large animal experiments and clinical trials are required to further explore the efficacy and safety of uPA in ICH fibrinolysis.

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Section: Discussionsupporting

confidence: 92%

Section: Experimental Groups and Fibrinolytic Therapymentioning

confidence: 99%

mentioning

confidence: 99%

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Urokinase, a promising candidate for fibrinolytic therapy for intracerebral hemorrhage

Tan

Chen

Niu

et al. 2017

JNS

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“…So far, tPA is the most widely used fibrinolytic agent for IVH and ICH ( 33 ). However, increased evidence indicated that uPA was able to increase the rate of clot lysis without exacerbation of PHE, and improve outcomes in patients with spontaneous ICH ( 34 , 35 ). Notably, Gaberel et al demonstrated that, in contrast to tPA, uPA displayed a safer profile for intraventricular fibrinolysis following IVH regarding secondary inflammatory processes and neurotoxicity, as well as better neurological outcome in experimental models of IVH ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Urokinase vs Tissue-Type Plasminogen Activator for Thrombolytic Evacuation of Spontaneous Intracerebral Hemorrhage in Basal Ganglia

Yang

et al. 2017

Front. Neurol.

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Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke, which leads to a high rate of mortality and poor neurological outcomes worldwide. Thrombolytic evacuation with urokinase-type plasminogen activator (uPA) or tissue-type plasminogen activator (tPA) has been showed to be a hopeful treatment for ICH. However, to the best of our knowledge, no clinical trials were reported to compare the efficacy and safety of these two fibrinolytics administrated following minimally invasive stereotactic puncture (MISP) in patients with spontaneous basal ganglia ICH. Therefore, the authors intended here to evaluate the differential impact of uPA and tPA in a retrospective study. In the present study, a total of 86 patients with spontaneous ICH in basal ganglia using MISP received either uPA (uPA group, n = 45) or tPA (tPA group, n = 41), respectively. The clinical baseline characteristics prior to the operation were collected. In addition, therapeutic responses were assessed by the short-term outcomes within 30 days postoperation, as well as long-term outcomes at 1 year postoperation. Our findings showed that, in comparison with tPA, uPA was able to better promote hematoma evacuation and ameliorate perihematomal edema, but the differences were not statistically significant. Moreover, the long-term functional outcomes of both groups were similar, with no statistical difference. In conclusion, these results provide evidence supporting that uPA and tPA are similar in the efficacy and safety for thrombolytic evacuation in combination with MISP in patients with spontaneous basal ganglia ICH.

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“…Therefore, in recent years, UK, an older thrombolytic drug, has re-emerged as a potential fibrinolytic treatment 1,5,18) . Furthermore, a large number of studies have reported that UK thrombolysis following SICH both increases clot resolution rate and improves clinical outcome 2,3,7,18,20) .…”

Section: Introductionmentioning

confidence: 99%

In-Vitro Study of Urokinase Thrombolysis Following Stereotactic Aspiration of Intracerebral Hematoma

Son

Park

Kang

et al. 2020

J Korean Neurosurg Soc

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Objective : A consensus regarding the ideal regimen for urokinase (UK) thrombolysis subsequent to stereotactic spontaneous intracerebral hemorrhage aspiration has yet to be established. The purpose of this study is to evaluate the efficacy of UK thrombolysis relative to when the regimen is changed. Methods : Venous blood from 30 heathy volunteers was obtained for this in-vitro study. Various concentrations of UK solution were added to microcentrifuge tubes containing the clotted blood. The efficacy of UK thrombolysis was identified by checking the weight of lysed hematoma following various time intervals with different concentrations of UK solution. Group one, the "3×4" group involved four administrations every 3 hours over 12 hours, and group two, the "6×2" group involved two administrations every 6 hours over 12 hours. Results : More hematoma was lysed in the 3×4 group than the 6×2 group across all concentration levels (however, the differences were only significant between groups at the 500 and 1000 IU concentration levels, p<0.05). There were no significant differences of lysed hematoma among the various UK solution concentrations within groups. Conclusion : This study suggests that frequent administrations of UK thrombolysis may result in a greater degree of lysed hematoma in comparison to a higher concentration of UK. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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No exacerbation of perihematomal edema with intraclot urokinase in patients with spontaneous intracerebral hemorrhage

Abstract: Hematoma evacuation using MIS leads to a significant reduction in PHE. Furthermore, the use of urokinase does not exacerbate PHE, making its hypothesized proedematous effects unlikely when the thrombolytic is administered directly into the clot.

Cited by 9 publications

References 28 publications

Urokinase, a promising candidate for fibrinolytic therapy for intracerebral hemorrhage

Urokinase, a promising candidate for fibrinolytic therapy for intracerebral hemorrhage

Urokinase vs Tissue-Type Plasminogen Activator for Thrombolytic Evacuation of Spontaneous Intracerebral Hemorrhage in Basal Ganglia

In-Vitro Study of Urokinase Thrombolysis Following Stereotactic Aspiration of Intracerebral Hematoma

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