Direct endovascular treatment versus bridging therapy in patients with acute ischemic stroke eligible for intravenous thrombolysis: systematic review and meta-analysis

ObjectiveIn this review and meta-analysis we sought to compare the efficacy and safety of direct endovascular thrombectomy (EVT) and bridging therapy for intravenous thrombolysis (IVT)-eligible patients with acute ischemic stroke caused by large vessel occlusions (AIS-LVO).MethodsWe searched Medline, Embase, and the Cochrane Library for published randomized clinical trials (RCTs) and observational studies providing outcomes of patients with IVT-eligible AIS-LVO who have undergone EVT with or without IVT. The primary outcome was the proportion of patients achieving a modified Rankin Scale (mRS) score of 0–2 at 90 days. The secondary outcomes included the rates of (1) an excellent outcome defined as an mRS score of 0 or 1 at 90 days, (2) mortality at 90 days, (3) symptomatic intracranial hemorrhage (sICH), (4) any type of intracranial hemorrhage (ICH), (5) successful recanalization, and (6) clot migration.ResultsWe included three RCTs and six observational studies (4 of which were propensity score-adjusted studies) with a total of 3133 patients. In unadjusted and adjusted analyses, no differences in the rates of mRS scores 0–2, mRS scores 0–1, mortality at 90 days, sICH or successful recanalization were detected between patients with AIS-LVO who underwent direct EVT or bridging therapy. The patients treated with direct EVT had a lower risk ratio for any type of ICH and clot migration than did the patients treated with bridging therapy.ConclusionCompared with bridging therapy, direct EVT may be equally effective and yield a lower rate of ICH and clot migration in patients with AIS.Trail registration numberPROSPERO: CRD42021236691.

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Tenecteplase versus alteplase for acute ischemic stroke thrombolysis: a systematic review and meta-analysis

Neurology Asia ◽

10.54029/2021mzi ◽

2021 ◽

Vol 26 (4) ◽

pp. 671-683

Author(s):

YinQin Hu ◽

YangBo Hou ◽

Zhen Chen ◽

Qian Xiao ◽

Huixia Chen ◽

...

Keyword(s):

Systematic Review ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Meta Analysis ◽

Intravenous Thrombolysis ◽

Cochrane Library ◽

Nihss Score ◽

Thrombolytic Drug ◽

Symptomatic Intracranial Hemorrhage

Background: Intravenous thrombolysis is the preferred clinical treatment for acute ischemic stroke. Alteplase is an intravenous thrombolytic drug used in clinical practice. Recently, studies have shown the efficacy of another intravenous thrombolytic drug, tenecteplase, and have reported that the risk of bleeding is low. However, at present, Chinese and international research has yielded controversial results regarding the efficacy and risks of tenecteplase. Therefore, this systematic review and meta- analysis of the efficacy and safety of tenecteplase were performed. Methods: PubMed, the Cochrane Library, MEDLINE, the Wanfang Database and CNKI were searched for all studies on the thrombolytic treatment of acute ischemic stroke. All studies published in English prior to March 2021 were retrieved. The studies were screened and selected based on the inclusion and exclusion criteria. Then, the data were extracted and recorded by trained researchers. RevMan 5.4 statistical software was used to analyze the data on the 24h recanalization rate, early neurological improvement (24h reduction in the National Institutes of Health Stroke Scale [NIHSS] score of at least 8 points or 24 h NIHSS score of 0~1 point), mRS score at 90 days, intracranial hemorrhage, symptomatic intracranial hemorrhage and mortality in the tenecteplase group and alteplase group. Results: A total of 565 related studies were identified through the initial searches in each database. The citations of meta-analyses and related reviews were screened for additional eligible articles. Eventually, 9 high-quality English-language articles that included 2149 patients with acute ischemic stroke (including 1035 in the tenecteplase group and 1046 in the alteplase group)were included in this meta-analysis. The meta-analysis results were as follows: (1) Efficacy: The 24 h recanalization rate with regard to vascular recanalization was significantly better in the tenecteplase group than in the alteplase group(OR = 1.83, 95% CI: 1.23~2.72, z = 2.97, P = 0.003). There was significantly greater improvement in early neurological function in the tenecteplase group than in the alteplase group (OR= 1.34, 95% CI: 1.11~1.63, Z=3.00, P =0.003). There were no significant differences in 90-day mRS scores between the two groups (mRS score =0-1, OR = 1.20, 95% CI: 0.99~1.46, z = 1.82, p = 0.07; mRS score =0-2, OR = 1.17, 95% CI: 0.94~1.45, z = 1.38, p = 0.17). However, the subgroup analysis showed that the 90-day mRS score of the 0.25 mg/kg tenecteplase group was significantly different from that of groups treated with other doses of tenecteplase (OR = 1.48, 95% CI: 1.01~2.03, z = 2.03, p = 0.04). (2) Safety: The incidences of any intracranial hemorrhage (OR = 0.91, 95% Ci: 0.55~1.49, z = 0.39, p = 0.70), symptomatic intracranial hemorrhage (OR = 1.21, 95% CI: 0.63~2.32, z = 0.56 P = 0.57), and mortality (OR = 0.85, 95% CI: 0.57~1.26, z = 0.82, p = 0.41) were not significantly different between the tenecteplase and alteplase groups. Conclusions: Tenecteplase can significantly increase the 24-hour vascular recanalization rate and improve the neurological prognosis of patients with acute ischemic stroke and it does not increase the risk of intracranial hemorrhage or mortality.

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Intravenous Thrombolysis Before Mechanical Thrombectomy for Acute Ischemic Stroke: A Meta‐Analysis

Journal of the American Heart Association ◽

10.1161/jaha.121.022303 ◽

2021 ◽

Author(s):

Houwei Du ◽

Hanhan Lei ◽

Gareth Ambler ◽

Shuangfang Fang ◽

Raoli He ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Intracranial Hemorrhage ◽

Mechanical Thrombectomy ◽

Meta Analysis ◽

Intravenous Thrombolysis ◽

Bridging Therapy ◽

Randomized Controlled ◽

Symptomatic Intracranial Hemorrhage

Background Whether intravenous thrombolysis before mechanical thrombectomy provides additional benefit for functional outcome in acute ischemic stroke remains uncertain. We performed a meta‐analysis to compare the outcomes of direct mechanical thrombectomy (dMT) to mechanical thrombectomy with bridging using intravenous thrombolysis (bridging therapy [BT]) in patients with acute ischemic stroke. Methods and Results We performed a literature search in the PubMed, Excerpta Medica database, and Cochrane Central Register of Controlled Trials from January 1, 2003, to April 26, 2021. We included randomized clinical trials and observational studies that reported the 90‐day functional outcome in patients with acute ischemic stroke undergoing dMT compared with BT. The 12 included studies (3 randomized controlled trials and 9 observational studies) yielded 3924 participants (mean age, 68.0 years [SD, 13.1 years]; women, 44.2%; 1887 participants who received dMT and 2037 participants who received BT). A meta‐analysis of randomized controlled trial and observational data revealed similar 90‐day functional independence (odds ratio [OR], 1.04; 95% CI, 0.90–1.19), mortality (OR, 1.03; 95% CI, 0.78–1.36), and successful recanalization (OR, 0.93; 95% CI, 0.76–1.14) for patients treated with dMT or BT. Compared with those in the BT group, patients in the dMT group were less likely to experience symptomatic intracranial hemorrhage (OR, 0.68; 95% CI, 0.51–0.91; P =0.008) or any intracranial hemorrhage (OR, 0.71; 95% CI, 0.61–0.84; P <0.001). Conclusions In this meta‐analysis of patients with acute ischemic stroke, we found no significant differences in 90‐day functional outcome or mortality between dMT and BT, but a lower rate of symptomatic intracranial hemorrhage for dMT. These findings support the use of dMT without intravenous thrombolysis bridging therapy. Registration URL: https://www.crd.york.ac.uk/prospero/ ; Unique identifier: 42021234664.

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Meta-analysis of the Smoker’s Paradox in Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis or Endovascular Treatment

Nicotine & Tobacco Research ◽

10.1093/ntr/ntz094 ◽

2019 ◽

Vol 21 (9) ◽

pp. 1181-1188 ◽

Cited By ~ 1

Author(s):

Peng Zhang ◽

Zhen-Ni Guo ◽

Xin Sun ◽

Yingkai Zhao ◽

Yi Yang

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Functional Outcomes ◽

Meta Analysis ◽

Intravenous Thrombolysis ◽

Cochrane Library ◽

Stroke Patients ◽

Good Functional Outcome

Abstract Introduction The existence of the smoker’s paradox is controversial and potential mechanisms have not been explained. We aimed to explore the association between cigarette smoking and functional outcome at 3 months in patients with acute ischemic stroke who were treated with intravenous thrombolysis (IVT) or endovascular treatment (EVT). Methods This meta-analysis was conducted in accordance with the PRISMA guidelines. Studies exploring the association between smoking and good functional outcome (modified Rankin Scale score ≤ 2) following IVT or EVT were searched via the databases of PubMed, Embase, and the Cochrane Library from inception to August 8, 2018. Information on the characteristics of included studies was independently extracted by two investigators. Data were pooled using a random-effects or fixed-effects meta-analysis according to the heterogeneity of included studies. Results Among 20 identified studies, 15 reported functional outcomes following IVT, and five reported functional outcomes following EVT. Unadjusted analyses showed that smoking increased the odds of good functional outcomes with a pooled odds ratio (OR) of 1.48 (95% confidence interval [CI]: 1.36–1.60) after IVT and 2.10 (95% CI: 1.47–3.20) after EVT. Of IVT studies, only eight reported outcomes adjusted for covariates and none of the EVT studies reported adjusted outcomes. After adjustment, the relation between smoking and good functional outcome following IVT lost statistical significance (OR 1.14 [95% CI: 0.81–1.59]). Conclusion Our meta-analysis suggested that smoking was not associated with good functional outcome (mRS ≤ 2) at 3 months in patients with acute ischemic stroke who were treated with intravenous thrombolysis. Implications The existence of the smoker’s paradox is controversial. A previous letter by Plas et al. published in 2013 reported a positive result for the association between smoking and good functional outcome at 3 months in acute ischemic stroke patients who received intravenous thrombolysis (IVT). However, a major limitation of their meta-analysis was that the process of data synthesis was based on unadjusted data. Therefore, we conducted this meta-analysis to investigate the association based on adjusted data and a larger sample size. Our meta-analysis suggested that smoking was not associated with good functional outcome after adjusting for covariates.

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Endovascular thrombectomy without versus with intravenous thrombolysis in acute ischemic stroke: a non-inferiority meta-analysis of randomized clinical trials

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2021-017667 ◽

2021 ◽

pp. neurintsurg-2021-017667

Author(s):

Chun-Hsien Lin ◽

Jeffrey L Saver ◽

Bruce Ovbiagele ◽

Wen-Yi Huang ◽

Meng Lee

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Randomized Trials ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Intravenous Thrombolysis ◽

Functional Independence ◽

Risk Difference ◽

Endovascular Thrombectomy ◽

Symptomatic Intracranial Hemorrhage

ObjectiveTo conduct a meta-analysis of randomized trials to comprehensively compare the effect of endovascular thrombectomy (EVT) versus intravenous thrombolysis (IVT) plus EVT on functional independence (modified Rankin Scale (mRS) 0–2) after acute ischemic stroke due to large vessel occlusions (AIS-LVO).MethodsWe searched Pubmed, EMBASE, CENTRAL, and clinicaltrials.gov from January 2000 to February 2021 and abstracts presented at the International Stroke Conference in March 2021 to identify trials comparing EVT alone versus IVT plus EVT in AIS-LVO. Five non-inferiority margins established in the literature were assessed: −15%, −10%, −6.5%, −5%, and −1.3% for the risk difference for functional independence at 90 days.ResultsFour trials met the selection criteria, enrolling 1633 individuals, with 817 participants randomly assigned to EVT alone and 816 to IVT plus EVT. Crude cumulative rates of 90-day functional independence were 46.0% with EVT alone versus 45.5% with IVT plus EVT. Pooled results showed the risk difference of functional independence was 1% (95% CI −4% to 5%) between EVT alone versus IVT plus EVT. The lower 95% CI bound of −4% fell within the non-inferiority margins of −15%, −10%, −6.5%, and −5%, but not −1.3%. Pooled results also showed the risk difference between EVT alone versus IVT plus EVT was 1% (95% CI −3% to 5%) for mRS 0–1, and 1% (95% CI −1% to 3%) for symptomatic intracranial hemorrhage.ConclusionsThis meta-analysis suggests that EVT alone is non-inferior to IVT plus EVT for several, but not the most stringent, non-inferiority margins.

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Abstract 106: Safety and Efficacy of Sonothrombolysis in Acute Ischemic Stroke Patients With Large Vessel Occlusion: International Collaborative Individual Patient Data Meta-Analysis

Stroke ◽

10.1161/str.51.suppl_1.106 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Georgios Tsivgoulis ◽

Aristeidis H Katsanos ◽

Jürgen Eggers ◽

Vincent Larrue ◽

Lars Thomassen ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Meta Analysis ◽

Intravenous Thrombolysis ◽

Functional Independence ◽

Large Vessel ◽

Large Vessel Occlusion ◽

Vessel Occlusion ◽

Safety And Efficacy

Introduction: Conflicting evidence has been published regarding the safety and efficacy of ultrasound-enhanced thrombolysis (sonothrombolysis) in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). Methods: We conducted an individual participant data meta-analysis of available randomized controlled trials (RCTs) comparing sonothrombolysis with or without addition of microspheres (treatment group) to intravenous thrombolysis alone (control group) in AIS patients with LVO. Results: We included 6 in total RCTs that enrolled 1077 AIS patients. A total of 138 and 134 confirmed LVO patients were randomized to treatment and control groups respectively (median age 68 years, 58% men, median baseline NIHSS score 16). Patients randomized to sonothrombolysis had increased odds of complete recanalization compared to patients receiving intravenous thrombolysis alone (40.3% vs. 22.4%; OR=2.30, 95%CI: 1.05-5.02; adjusted OR=2.33, 95%CI: 1.02-5.34). They also tended to have increased odds of any (complete or partial recanalization (66.4% vs. 53.0%; OR=1.78, 95%CI: 0.95-3.33; adjusted OR=1.85, 95%CI: 0.97-3.53). The likelihood of symptomatic intracranial hemorrhage did not differ between the two groups (7.3% vs. 3.7%, OR=2.52, 95%CI: 0.77-8.29; adjusted OR=2.55, 95%CI: 0.76-8.52). No differences in the likelihood of asymptomatic intracranial hemorrhage (adjusted OR: 1.30, 95%CI: 0.38-4.39), three-month mortality (adjusted OR: 1.23, 95%CI: 0.25-6.05), three-month favorable functional outcome (mRS-scores of 0-1; adjusted OR: 1.43, 95%CI: 0.64-3.19) and three-month functional independence (mRS-scores of 0-2; adjusted OR: 1.43, 95%CI: 0.77-2.64) were documented. Conclusion: Sonothrombolysis was associated with a two-fold increase in the odds of complete recanalization compared to intravenous thrombolysis alone in AIS patients with LVOs. Further study of the safety and efficacy of sonothrombolysis is warranted.

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Abstract 185: Association of Antiplatelet Pretreatment With Outcomes in Acute Ischemic Stroke Patients Treated With Intravenous Thrombolysis: A Systematic Review and Meta-analysis of Randomized Clinical Trials

Stroke ◽

10.1161/str.48.suppl_1.185 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Georgios Tsivgoulis ◽

Aristeidis H Katsanos ◽

Ramin Zand ◽

Vijay K Sharma ◽

Martin Köhrmann ◽

...

Keyword(s):

Systematic Review ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Randomized Clinical Trials ◽

Controlled Trial ◽

Meta Analysis ◽

Intravenous Thrombolysis ◽

Functional Independence ◽

Adverse Outcomes ◽

Stroke Severity

Background & Purpose: In a recent randomized controlled trial (RCT) of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) antiplatelet pre-treatment (APP) was associated with adverse outcomes. We conducted a systematic review and meta-analysis of available RCTs to investigate the association of APP with outcomes of AIS patients treated with IVT. Methods: The outcome events of interest included symptomatic intracranial hemorrhage (sICH), complete recanalization (CR), 3-month favorable functional outcome (FFO, mRS-score: 0-1), functional independence (FI, mRS-score: 0-2), and mortality. Both unadjusted and adjusted (for baseline stroke severity and age) analyses were performed using random effects methodology. Results: We included 8 RCTs (5,332 total patients, 34% with APP). In unadjusted analyses (Figure 1), APP was associated with higher likelihood of sICH (OR=2.01, 95%CI: 1.53-2.63) and death (OR=1.59, 95%CI: 1.24-2.03; 1C) and lower likelihood of 3-month FI (OR=0.69, 0.56-0.85). No association was detected between APP and 3-month FFO (OR=0.79, 95%CI: 0.58-1.07) and CR (OR=0.64, 95%CI: 0.04-11.66). In adjusted analyses (Figure 2), APP was related to higher odds of sICH (OR=1.89, 95%CI: 1.14-3.12). There was no association between APP and 3-month FI (OR=0.94, 95%CI: 0.70-1.26) or death (OR=1.01, 95%CI: 0.55-1.86). In all analyses no evidence of heterogeneity was detected. Conclusion: Despite APP association with a higher risk of sICH after thrombolysis, three-month functional outcomes appear un-affected by APP. APP before IVT should not be used as an excuse to withhold or to lower the dose of IVT.

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Direct Endovascular Thrombectomy or With Prior Intravenous Thrombolysis for Acute Ischemic Stroke: A Meta-Analysis

Frontiers in Neurology ◽

10.3389/fneur.2021.752698 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jing Chen ◽

Teng-Fei Wan ◽

Tian-Ce Xu ◽

Guo-Can Chang ◽

Hui-Sheng Chen ◽

...

Keyword(s):

Ischemic Stroke ◽

Randomized Controlled Trials ◽

Acute Ischemic Stroke ◽

Meta Analysis ◽

Intravenous Thrombolysis ◽

Functional Independence ◽

Controlled Trials ◽

Endovascular Thrombectomy ◽

Excellent Outcome ◽

Randomized Controlled

Background and purpose: It is unclear whether endovascular thrombectomy alone compared with intravenous thrombolysis combination with endovascular thrombectomy can achieve similar neurological outcomes in patients with acute large vessel occlusion stroke. We aimed to perform a systematic review and meta-analysis of randomized controlled trials to compare endovascular thrombectomy alone or intravenous thrombolysis plus endovascular thrombectomy in this population.Methods: We systematically searched PubMed, Embase, and ClinicalTrials.gov. We restricted our search to randomized clinical trials that examined the clinical outcomes of endovascular thrombectomy alone vs. intravenous thrombolysis plus endovascular thrombectomy. The Cochrane risk of bias tool was used to assess study quality. Random-effects meta-analyses were used for evaluating all outcomes.Results: Total three randomized controlled trials with 1,092 individuals enrolled were included in the meta-analysis, including 543 (49.7%) who received endovascular thrombectomy alone and 549 (50.3%) who received intravenous thrombolysis plus endovascular thrombectomy. The primary outcome of 90-day functional independence (modified Rankin scale (mRS) score ≤ 2) was 44.6% (242/543) in the endovascular thrombectomy alone group vs. 42.8% (235/549) in the alteplase with endovascular thrombectomy group (odds ratio (OR), 1.08 [95% CI, 0.85–1.38]; P = 0.0539). Among pre-specified secondary outcomes, no significant between-group differences were found in excellent outcome (mRS score ≤ 1) (OR, 1.12 [95% CI, 0.85–1.47]; P = 0.418), mortality at 90 days (OR, 0.93 [95% CI, 0.68–1.29]; P = 0.673), successful reperfusion (thrombolysis in cerebral infarction 2b-3) (OR, 0.75 [95% CI, 0.54–1.05]; P = 0.099), and symptomatic intracranial hemorrhage (OR, 0.72 [95% CI, 0.45–1.15]; P = 0.171).Conclusions: Among patients with acute ischemic stroke in the anterior circulation within 4.5 h from the onset, endovascular thrombectomy alone was non-inferior to combined intravenous thrombolysis and endovascular thrombectomy.

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Efficacy and Safety of rt-PA Intravenous Thrombolysis in Patients with Wake-up Stroke: A Meta-Analysis

10.21203/rs.3.rs-371117/v1 ◽

2021 ◽

Author(s):

Hongfa Liu ◽

Jianghong Luo ◽

Fang Zhang ◽

Ziliang Zhang ◽

Wei Gu ◽

...

Keyword(s):

Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Fixed Effects ◽

Meta Analysis ◽

Intravenous Thrombolysis ◽

Recombinant Tissue Plasminogen Activator ◽

Cochrane Library ◽

Efficacy And Safety ◽

Fixed Effects Model ◽

Safety Outcomes

Abstract Background Recombinant tissue plasminogen activator (rt-PA) is one of the most effective therapies for patients with acute ischemic stroke. However, wake-up stroke (WUS) is typically excluded from intravenous thrombolytic therapy because the time of symptom onset is unclear. Therefore, we aimed to assess the efficacy and safety of rt-PA intravenous thrombolysis in patients with WUS by meta-analysis. Methods We completed a systematic literature search of PubMed, Embase, the Cochrane Library, and SinoMed and included relevant studies of WUS patients covering rt-PA thrombolysis and nonthrombolysis (published from January 1, 2000, to February 28, 2021, with no language restrictions). Primary outcomes included safety outcomes and functional outcomes. Safety outcomes was measured according to the incidence of symptomatic intracranial hemorrhage (SICH) and mortality within 90 days. Efficacy outcomes was measured based on 90-day modified Rankin Scale (mRS) score. We assessed pooled data using either a random-effects model (when P < 0.10, I2 > 50%) or a fixed-effects model (when P > 0.10, I2 < 50%). Results Nine studies with 913 patients were included in the meta-analysis. All patients had ischemic stroke confirmed by computed tomography or magnetic resonance imaging. The incidence of mRS 0–2 was significantly higher in the rt-PA thrombolysis group compared with the nonthrombolysis group. And rt-PA thrombolytic WUS patients did not differ significantly from nonthrombolytic WUS patients in terms of 90-day mortality. However, the rate of SICH was also significantly higher in the rt-PA thrombolysis group than that in the nonthrombolysis group. Conclusions Patients with WUS who received rt-PA thrombolysis had a significant positive effect within 90 days. In addition, although there is no significant increase in mortality, we need to be aware of the risk of intracranial hemorrhage transformation associated with rt-PA thrombolysis despite no obvious increase in mortality. The safety of rt-PA intravenous thrombolysis should be closely monitored in patients with WUS.

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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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Recanalisation theraphy for acute ischemic stroke in cancer patients

Scientific Reports ◽

10.1038/s41598-021-91257-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Giovanni Merlino ◽

Carmelo Smeralda ◽

Gian Luigi Gigli ◽

Simone Lorenzut ◽

Sara Pez ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Metastatic Cancer ◽

Intravenous Thrombolysis ◽

Functional Independence ◽

University Hospital ◽

Bridging Therapy ◽

Patients With Cancer ◽

Increased Risk ◽

Active Cancer

AbstractTo date, very few studies focused their attention on efficacy and safety of recanalisation therapy in acute ischemic stroke (AIS) patients with cancer, reporting conflicting results. We retrospectively analysed data from our database of consecutive patients admitted to the Udine University Hospital with AIS that were treated with recanalisation therapy, i.e. intravenous thrombolysis (IVT), mechanical thrombectomy (MT), and bridging therapy, from January 2015 to December 2019. We compared 3-month dependency, 3-month mortality, and symptomatic intracranial haemorrhage (SICH) occurrence of patients with active cancer (AC) and remote cancer (RC) with that of patients without cancer (WC) undergoing recanalisation therapy for AIS. Patients were followed up for 3 months. Among the 613 AIS patients included in the study, 79 patients (12.9%) had either AC (n = 46; 7.5%) or RC (n = 33; 5.4%). Although AC patients, when treated with IVT, had a significantly increased risk of 3-month mortality [odds ratio (OR) 6.97, 95% confidence interval (CI) 2.42–20.07, p = 0.001] than WC patients, stroke-related deaths did not differ between AC and WC patients (30% vs. 28.8%, p = 0.939). There were no significant differences between AC and WC patients, when treated with MT ± IVT, regarding 3-month dependency, 3-month mortality and SICH. Functional independence, mortality, and SICH were similar between RC and WC patients. In conclusion, recanalisation therapy might be used in AIS patients with nonmetastatic AC and with RC. Further studies are needed to explore the outcome of AIS patients with metastatic cancer undergoing recanalisation therapy.

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