Tissue Plasminogen Activator Therapy Research Articles

The Use of Recombinant Tissue Plasminogen Activator in the Management of Paediatric Cardiac Thrombosis: A Single-centre Experience

Objectives: Recombinant tissue plasminogen activator (rTPA) therapy for the treatment of intravascular thrombosis has a reported complication rates of up to 40%. This study retrospectively reviewed the rate of thrombus resolution and complications of all patients who received systemic rTPA from May 2008 to March 2018.

Alberta Stroke Program Early CT Score-Time Score Predicts Outcome after Endovascular Therapy in Patients with Acute Ischemic Stroke: A Retrospective Single-Center Study

Clinical outcomes after successful endovascular therapy in patients with acute ischemic stroke are associated with several factors including onset-to-reperfusion time (ORT), the National Institute of Health Stroke Scale (NIHSS) score, and the Alberta Stroke Program Early CT Score (ASPECTS). The NIHSS-time score, calculated as follows: [NIHSS score] × [onset-to-treatment time (h)] or [NIHSS score] × [ORT (h)], has been reported to predict clinical outcomes after intravenous recombinant tissue plasminogen activator therapy and endovascular therapy for acute stroke. The objective of the current study was to assess whether the combination of the ASPECTS and the ORT can predict the outcomes after endovascular therapy. The charts of 117 consecutive ischemic stroke patients with successful reperfusion after endovascular therapy were retrospectively reviewed. We analyzed the association of ORT, ASPECTS, and ASPECTS-time score with clinical outcome. ASPECTS-time score was calculated as follows: [11 - ASPECTS] × [ORT (h)]. Rates of good outcome for patients with ASPECTS-time scores of tertile values, scores 5.67 or less, scores greater than 5.67 to 10.40 or less, and scores greater than 10.40, were 66.7%, 56.4%, and 33.3%, respectively (P < .05). Ordinal logistic regression analysis showed that the ASPECTS-time score (per category increase) was an independent predictor for better outcome (common odds ratio: .374; 95% confidence interval: .150-0.930; P < .05). A lower ASPECTS-time score may predict better clinical outcomes after endovascular treatment.

Investigation of intravenous recombinant tissue plasminogen activator(rt-PA) therapy and endovascular therapy at Aichi Medical University Hospital

Background: It is important to resume blood flow as early as possible for hyperacute treatment of cerebral infarction, intravenous(IV) rt-PA therapy is known as standard treatment. Meanwhile, good clinical outcome of endovascular therapy has been reported one after another in recent years, proving to be effective treatment like rt-PA. However, the trials that has been able to demonstrate effectiveness in large-scale trials confirmed to the patients who satisfy certain criteria, and its effectiveness and safety is unknown for patients who are out of the criteria.

Safety and Time Course of Drip-and-Ship in Treatment of Acute Ischemic Stroke

The drip-and-ship approach allows intravenous tissue plasminogen activator therapy and adjuvant endovascular treatment in acute ischemic stroke, even in rural areas. Here, we examined the safety and time course of the drip-and-ship approach. Fifty consecutive cases treated with the drip-and-ship approach (drip-and-ship group) in June 2009 to March 2016 were retrospectively examined. Changes in mean blood pressure, systemic complications, and neurological complications were compared according to method of transportation. Time courses were compared between drip-and-ship and direct admission groups during the same period. In the drip-and-ship group, 33 and 17 patients were transferred to hospital by ambulance and helicopter, respectively. One patient suffered hemorrhagic infarction during transportation by ambulance. Mean blood pressure change was lower in patients transferred by helicopter than ambulance (<5 mmHg versus 12.2 mmHg, respectively). The mean onset-to-door times in the drip-and-ship and direct admission groups were 71 and 64 minutes, respectively, and mean door-to-needle times were 70 and 47 minutes, respectively (P =.002). Although mean transportation time from the primary stroke hospital to our hospital was 32 minutes, the entry-to-exit time from the primary stroke hospital was 113 minutes. Thereafter, there was an average delay of 100 minutes until reperfusion compared with the direct admission group. Drip-and-ship was relatively safe in this small series. Transportation by helicopter was less stressful for acute ischemic stroke patients. It is important to reduce door-to-needle time and needle-to-departure time in the primary stroke hospital to minimize the time until treatment in cases of acute ischemic stroke.

Drip-and-Ship Thrombolytic Therapy for Acute Ischemic Stroke

Neuroendovascular therapy is a common treatment for patients with acute ischemic stroke of the anterior circulation who fail to respond to recombinant tissue plasminogen activator. However, although most hospitals can provide recombinant tissue plasminogen activator therapy, many cannot perform neuroendovascular therapy. Thus, use of a drip-and-ship treatment-liaison system allowing recombinant tissue plasminogen activator-treated patients to be transferred to facilities offering neuroendovascular therapy is important. We retrospectively analyzed 16 drip-and-ship patients transferred to our hospital for additional neuroendovascular therapy after they received intravenous recombinant tissue plasminogen activator at prior hospitals between June 2009 and March 2017. The mean patient age was 68 ± 17 years. Ten patients had cardiogenic embolism and 6 had atherothrombosis. Additional neuroendovascular therapy was performed in 14 patients. Median National Institute of Health Stroke Scale and diffusion-weighted image-Alberta Stroke Program Early Computed Tomography Scores before recombinant tissue plasminogen activator therapy were 14 and 8, respectively. Occluded or stenotic lesions of the cerebral arteries were detected by magnetic resonance angiography in the internal carotid artery (n = 4), middle cerebral artery (n = 10), and basilar artery (n = 3) (1 patient had tandem lesions). Mean intervals from onset-to-recombinant tissue plasminogen activator, recombinant tissue plasminogen activator-to-our hospital (door), door-to-puncture, and onset-to-recanalization were 166, 65, 32, and 334 minutes, respectively. No patients showed symptomatic intracranial hemorrhage. Magnetic resonance imaging/angiography performed in previous hospitals allows initiation of reperfusion therapy immediately after transfer. Thus, drip-and-ship plus neuroendovascular therapy is a safe and useful system for treatment of patients with acute infarcts.

Tirofiban facilitates the reperfusion process during endovascular thrombectomy in ICAS.

The aim of the present study was to assess the use of tirofiban injections for rescue therapy following artery reocclusion due to intra-luminal thrombosis during endovascular thrombectomy in patients with acute ischemic stroke (AIS). A total of seven cases of patients treated with adjunctive tirofiban injections following failed endovascular thrombectomy due to instant intra-luminal thrombosis were retrospectively assessed. A Solitaire stent was used as the primary thrombectomy device in all patients. Tirofiban was injected intra-arterially via a temporarily deployed Solitaire stent with continuous intravenous infusion for the subsequent 24 h; half of the conventionally recommended dose was employed. Outcome measures included angiographic reperfusion (mTICI), symptomatic intracranial hemorrhage, mortality and functional independence at 90 days (modified Rankin Scale, 0-2). Six patients had occlusions in the middle cerebral artery and one patient had occlusions in the basilar artery. Of the seven patients, five exhibited successful reperfusion (mTICI 2b-3) and achieved functional independence following 90 days. Reperfusion failed in the remaining two patients, who succumbed within 90 days of therapy. No intracranial or extracranial hemorrhage cases were identified. The results of the present study suggest that tirofiban facilitates reperfusion and ameliorates long-term prognosis in patients with AIS undergoing endovascular thrombectomy, and may be safe for those receiving intravenous tissue plasminogen activator therapy.

Fortifying the BBB: Border control by increasing regulators.

Treatment with exogenous regulatory T cells fortifies the blood-brain barrier after tissue plasminogen activator therapy in models of acute ischemic stroke.

Plasma kallikrein mediates brain hemorrhage and edema caused by tissue plasminogen activator therapy in mice after stroke

AbstractThrombolytic therapy using tissue plasminogen activator (tPA) in acute stroke is associated with increased risks of cerebral hemorrhagic transformation and angioedema. Although plasma kallikrein (PKal) has been implicated in contributing to both hematoma expansion and thrombosis in stroke, its role in the complications associated with the therapeutic use of tPA in stroke is not yet available. We investigated the effects of tPA on plasma prekallikrein (PPK) activation and the role of PKal on cerebral outcomes in a murine thrombotic stroke model treated with tPA. We show that tPA increases PKal activity in vitro in both murine and human plasma, via a factor XII (FXII)–dependent mechanism. Intravenous administration of tPA increased circulating PKal activity in mice. In mice with thrombotic occlusion of the middle cerebral artery, tPA administration increased brain hemorrhage transformation, infarct volume, and edema. These adverse effects of tPA were ameliorated in PPK (Klkb1)–deficient and FXII-deficient mice and in wild-type (WT) mice pretreated with a PKal inhibitor prior to tPA. tPA-induced brain hemisphere reperfusion after photothrombolic middle cerebral artery occlusion was increased in Klkb1−/− mice compared with WT mice. In addition, PKal inhibition reduced matrix metalloproteinase-9 activity in brain following stroke and tPA therapy. These data demonstrate that tPA activates PPK in plasma and PKal inhibition reduces cerebral complications associated with tPA-mediated thrombolysis in stroke.

ERic Acute StrokE Recanalization: A study using predictive analytics to assess a new device for mechanical thrombectomy.

Aim and hypothesis Using a new study design, we investigate whether next-generation mechanical thrombectomy devices improve clinical outcomes in ischemic stroke patients. We hypothesize that this new methodology is superior to intravenous tissue plasminogen activator therapy alone. Methods and design ERic Acute StrokE Recanalization is an investigator-initiated prospective single-arm, multicenter, controlled, open label study to compare the safety and effectiveness of a new recanalization device and distal access catheter in acute ischemic stroke patients with symptoms attributable to acute ischemic stroke and vessel occlusion of the internal cerebral artery or middle cerebral artery. Study outcome The primary effectiveness endpoint is the volume of saved tissue. Volume of saved tissue is defined as difference of the actual infarct volume and the brain volume that is predicted to develop infarction by using an optimized high-level machine learning model that is trained on data from a historical cohort treated with IV tissue plasminogen activator. Sample size estimates Based on own preliminary data, 45 patients fulfilling all inclusion criteria need to complete the study to show an efficacy >38% with a power of 80% and a one-sided alpha error risk of 0.05 (based on a one sample t-test). Discussion ERic Acute StrokE Recanalization is the first prospective study in interventional stroke therapy to use predictive analytics as primary and secondary endpoint. Such trial design cannot replace randomized controlled trials with clinical endpoints. However, ERic Acute StrokE Recanalization could serve as an exemplary trial design for evaluating nonpivotal neurovascular interventions.

P1-7 - Clinical evaluation of prognosis after intravenous recombinant tissue plasminogen activator therapy

P1-7 - Clinical evaluation of prognosis after intravenous recombinant tissue plasminogen activator therapy

Abstract WP61: Volumetric DWI Malignant Profile Assessment in Acute Ischemic Patients With Reperfusion Therapy.

Background: The efficacy of endovascular therapy (EVT) in acute stroke has been established but the imaging criteria have not yet been assessed. Malignant profile is a magnetic resonance imaging (MRI) pattern that is associated with poor outcomes. We estimated this profile by volumetrically assessing diffusion weighted image (DWI) in patients treated with reperfusion therapy including intravenous tissue plasminogen activator (IV tPA) and endovascular therapy (EVT). Methods: Acute anterior ischemic stroke patients with baseline DWI before reperfusion therapy were included. Outcome was assessed by modified Rankin Scale (mRS) at discharge. DWI volume was measured by semi-automated software.Receiver operating characteristic (ROC) curve analysis was performed to identify optimal DWI volumes with poor outcome (mRS 5-6). Results: Total of 96 patients (43% women, mean age 72±13 years) were included in this study. Median (interquartile range: IQR) National Institutes of Health Stroke Scale was 9 (5-12) and median onset to MRI time was 108.5 (70-217) minutes. Median DWI volume was 4.4 (1.3-17) mL for overall patients. Median onset to IV tPA time for 60 (63%) patients were 120 (65-177) minutes. Median onset to puncture time for 36 (38%) EVT-treated patients was 208 (121.0-474.3) minutes; 29 of these 36 patients (81%) had Thrombolysis in Cerebral Infarction (TICI) score of 2B/3. Median discharge mRS was 2 (1-3) for overall and 6 cases (6%) had mRS 5-6. ROC analysis determined DWI volume with poor outcome as 49.5 mL (92.2% specificity and 50% sensitivity, AUC 0.75, p&lt;0.001). Conclusion: Our study suggests the optimal volume of the malignant profile on DWI was approximately 50mL in reperfusion therapy eligible patients. Clinical outcome of patients exceeding the cutoff volume were very poor. The imaging criteria for reperfusion therapy including EVT should be well considered to achieve better outcomes.

Abstract TP303: Institutional Stroke Quality Improvement and Impact on Vascular Neurology Fellows Practice Patterns

Background and objectives: The American Heart Association quality improvement (QI) program Target Stroke is focused on reducing door-to-needle (DTN) time for IV tissue plasminogen activator (tPA) therapy to ≤60 minutes. Multidisciplinary QI procedures similar to the Target Stroke best practices have been shown to improve DTN times at an MRI based program. Whether these strategies improve the performance of trainees is unclear. The objective of this study was to determine the impact of a multidisciplinary QI program on the practice patterns of vascular neurology (VN) fellows at an MRI based stroke program. Methods: Case logs from the NIH Stroke Program VN fellows (N=22) were reviewed from July 2008-July 2015. Data was collected for the following: total patients screened, patients triaged, stroke code proceeds, tPA treated cases, and door to needle time (DTN) for each patient treated including DTN ≤60 minutes. QI processes that included stroke team education and process changes were initiated in 2013 to improve stroke care at two hospitals where VN fellows provide clinical care. We compared VN fellow practice patterns before (2008-12) and after (2013-15) QI implementation. Results: A total of 5093 cases were reviewed for the study. From 2008-15, fellows screened a yearly average of 232 patients, triaged 54% (125) to acute imaging, and treated 7.8% (18) patients each year with IV tPA. VN fellow practice patterns after QI implementation (2013-15) improved for percent treated with IV tPA (5.8% vs. 9.9%, p&lt;0.05), median DTN (83 vs. 71 min.; p&lt;0.05), and percentage treated ≤60 minutes (11% vs. 40%; p&lt;0.05). The mean number of patients screened was slightly higher before 2013 (238 vs. 225), and triage rates were similar (52.4% vs. 55%, p=0.58). Conclusion: The results of this study suggest that an institutional multidisciplinary QI stroke program can improve the practice patterns of VN fellows at an MRI based stroke program.

Abstract WMP112: Safety and Efficacy of Intravenous Thrombolysis and Endovascular Therapy in Children with Acute Ischemic Stroke: A Systematic Review and Meta-analysis

Background: Although intravenous thrombolysis (IVT) with tissue plasminogen activator (tPA) and endovascular therapy (EVT) are considered standard-of-care treatment of acute ischemic stroke in adults, safety and efficacy of these treatment modalities in children is unknown to date. We reviewed current literature and synthesized data on safety and efficacy of IVT and EVT in children with ischemic stroke. Methods: We performed a systematic review and meta-analysis of all available case series and observational studies that evaluated safety of IVT and EVT in pediatric stroke patients aged less than 18 years. We searched the electronic databases Medline, PubMed, Cochrane Library, Google Scholar for eligible studies. Safety outcomes comprised any intracerebral hemorrhage post-treatment and in-hospital mortality. A random-effects model was used to compute pooled effect estimates and the I 2 statistic was used to assess heterogeneity. Our analysis complied with PRISMA statement. Results: We identified 152 records through database searching, of which only 3 studies with a total of 16,335 pediatric patients with ischemic stroke met our eligibility criteria. Of these studies, two explored safety of sole IVT and one combinatory IVT/EVT. In-hospital mortality rates were similar between pediatric stroke patients treated with either IVT or IVT/EVT and controls (odds ratio=0.85, 95%CI: 0.15-4.87; p=0.857), with moderate evidence of heterogeneity ( I 2 =64%). Risk of intracerebral hemorrhage was substantially increased in children receiving IVT (odds ratio=3.60, 95%CI: 1.66-7.80; p=0.001) compared with controls, with no evidence of heterogeneity ( I 2 =0%). Efficacy of revascularization therapies could not be analyzed due to lack of uniform outcome data in the included studies. Conclusions: Our synthesized data analysis revealed a substantial lack of evidence for acute revascularization treatment of children with ischemic stroke. While an increased risk of intracerebral hemorrhage related to IVT emerged in our analysis, further research is needed to elaborate these findings.

Abstract TP64: Intravenous Thrombolysis in Chinese Patients with Mild Stroke

Objectives: Thrombolysis treatment for patients with mild stroke is controversial. The aim of this study is to investigate whether patients with mild stroke or its specific etiologic subtype could benefit from recombinant tissue plasminogen activator (rt-PA) therapy. Methods: Data were derived from two cohorts of patients with and without rt-PA treatment: (1) the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China database and (2) the China National Stroke Registry database. Patients with mild stroke (defined as National Institutes of Health Stroke Scale≤5) receiving the rt-PA therapy and without rt-PA therapy were matched in 1:2 for age, sex, stroke severity and etiologic subtype. Good functional outcome was defined as modified Rankin Scale 0-1 at 3 months. Odds ratios (ORs) with 95 % confidence intervals (CIs) were estimated using conditional logistic regression in total patients and by etiologic subtype, respectively. Results: A total of 134 rt-PA treated patients were matched to 249 non-rt-PA treated patients in the study. Among them, 104 (76%) rt-PA-treated patients with mild stroke had good outcome after 3 months compared with 173 (69.5%) non-rt-PA-treated matching cases (odds ratio [OR], 1.48; 95% confidence interval [CI], 0.91-2.43; P=0.12). Compared with non-rt-PA treatment group, rt-PA-treated patients had good outcome after 3 months in those with stroke subtype of large-artery atherosclerosis (LAA) (80.5% vs 65.1%; OR, 2.19; 95%CI, 1.14-4.21; P=0.02). Conclusions: For patients with mild stroke, intravenous rt-PA treatment may be effective. Patients with stroke subtype of LAA could benefit more from intravenous rt-PA treatment.

Intravenous infusion of mesenchymal stem cells inhibits intracranial hemorrhage after recombinant tissue plasminogen activator therapy for transient middle cerebral artery occlusion in rats.

OBJECTIVE Reperfusion therapy with intravenous recombinant tissue plasminogen activator (rtPA) is the standard of care for acute ischemic stroke. However, hemorrhagic complications can result. Intravenous infusion of mesenchymal stem cells (MSCs) reduces stroke volume and improves behavioral function in experimental stroke models. One suggested therapeutic mechanism is inhibition of vascular endothelial dysfunction. The objective of this study was to determine whether MSCs suppress hemorrhagic events after rtPA therapy in the acute phase of transient middle cerebral artery occlusion (tMCAO) in rats. METHODS After induction of tMCAO, 4 groups were studied: 1) normal saline [NS]+vehicle, 2) rtPA+vehicle, 3) NS+MSCs, and 4) rtPA+MSCs. The incidence rate of intracerebral hemorrhage, both hemorrhagic and ischemic volume, and behavioral performance were examined. Matrix metalloproteinase-9 (MMP-9) levels in the brain were assessed with zymography. Quantitative analysis of regional cerebral blood flow (rCBF) was performed to assess hemodynamic change in the ischemic lesion. RESULTS The MSC-treated groups (Groups 3 and 4) experienced a greater reduction in the incidence rate of intracerebral hemorrhage and hemorrhagic volume 1 day after tMCAO even if rtPA was received. The application of rtPA enhanced activation of MMP-9, but MSCs inhibited MMP-9 activation. Behavioral testing indicated that both MSC-infused groups had greater improvement than non-MSC groups had, but rtPA+MSCs provided greater improvement than MSCs alone. The rCBF ratio of rtPA groups (Groups 2 and 4) was similar at 2 hours after reperfusion of tMCAO, but both were greater than that in non-rtPA groups. CONCLUSIONS Infused MSCs may inhibit endothelial dysfunction to suppress hemorrhagic events and facilitate functional outcome. Combined therapy of infused MSCs after rtPA therapy facilitated early behavioral recovery.

DRAGON score predicts functional outcomes in acute ischemic stroke patients receiving both intravenous tissue plasminogen activator and endovascular therapy

Background:The DRAGON score, which includes clinical and computed tomographic (CT) scan parameters, predicts functional outcomes in ischemic stroke patients treated with intravenous tissue plasminogen activator (IV tPA). We assessed the utility of the DRAGON score in predicting functional outcome in stroke patients receiving both IV tPA and endovascular therapy.Methods:A retrospective chart review of patients treated at our institution from February 2009 to October 2015 was conducted. All patients with computed tomography angiography (CTA) proven large vessel occlusions (LVO) who underwent intravenous thrombolysis and endovascular therapy were included. Baseline DRAGON scores and modified Rankin Score (mRS) at the time of hospital discharge was calculated. Good outcome was defined as mRS ≤3.Results:Fifty-eight patients with LVO of the anterior circulation were studied. The mean DRAGON score of patients on admission was 5.3 (range, 3–8). All patients received IV tPA and endovascular therapy. Multivariate analysis demonstrated that DRAGON scores ≥7 was associated with higher mRS (P < 0.006) and higher mortality (P < 0.0001) compared with DRAGON scores ≤6. Patients with DRAGON scores of 7 and 8 on admission had a mortality rate of 3.8% and 40%, respectively.Conclusions:The DRAGON score can help predict better functional outcomes in ischemic stroke patients receiving both IV tPA and endovascular therapy. This data supports the use of the DRAGON score in selecting patients who could potentially benefit from more invasive therapies such as endovascular treatment. Larger prospective studies are warranted to further validate these results.

Recombinant Tissue Plasminogen Activator Therapy for the Patient with Acute Cerebral Infarction After Endobronchial Ultrasound-guided Transbronchial Needle Aspiration: a Case Report

Recombinant Tissue Plasminogen Activator Therapy for the Patient with Acute Cerebral Infarction After Endobronchial Ultrasound-guided Transbronchial Needle Aspiration: a Case Report

General Anesthesia During Endovascular Stroke Therapy Does Not Negatively Impact Outcome.

Recent randomized trials have demonstrated that endovascular therapy improves outcomes in patients with an acute ischemic stroke from a large vessel occlusion. Subgroup analysis of the Multicenter Randomized CLinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) study found that patients undergoing general anesthesia (GA) for the procedure did worse than those with nongeneral anesthesia (non-GA). Current guidelines now suggest that we consider non-GA over GA, without large, randomized trials specifically designed to address this issue. We sought to review our experience and outcomes in a program where we routinely use GA in patients undergoing mechanical thrombectomy with similar techniques. Patients with anterior circulation strokes who received intravenous tissue plasminogen activator (IV-tPA) and endovascular stroke therapy were included in the analysis. The National Institutes of Health Stroke Scale (NIHSS) on admission and discharge and modified Rankin scale scores at discharge were recorded and compared with the outcome measurements of MR CLEAN. Sixty patients were identified: 39 males and 21 females with a mean age of 62 (range of 29-88). Forty-seven patients were transferred from outside primary stroke centers, while 13 patients presented directly to our institution. Median NIHSS on admission was 15. The median time of symptom onset to endovascular therapy was 265 minutes, with an interquartile range of 81 minutes. Using the thrombolysis in cerebral infarction (TICI) scale, recanalization of TICI 2b-3 was achieved in 76.4% of recorded patients (42/55 recorded). At discharge, mortality was 16.7% (10/60), median NIHSS was 5, and 38.3% (23/60) of patients had a modified Rankin Scale score of 0-2. General anesthesia does not worsen outcome in patients undergoing mechanical thrombectomy when compared to historical subgroups. Despite a longer time from symptom onset to treatment, our outcomes for patients receiving GA compare favorably to the GA and non-GA groups in MR CLEAN.

Prestroke Antiplatelet Effect on Symptomatic Intracranial Hemorrhage and Functional Outcome in Intravenous Thrombolysis.

Background and PurposeAbout 30%-40% of stroke patients are taking antiplatelet at the time of their strokes, which might increase the risk of symptomatic intracranial hemorrhage (SICH) with intravenous tissue plasminogen activator (IV-TPA) therapy. We aimed to assess the effect of prestroke antiplatelet on the SICH risk and functional outcome in Koreans treated with IV-TPA.MethodsFrom a prospective stroke registry, we identified patients treated with IV-TPA between October 2009 and November 2014. Prestroke antiplatelet use was defined as taking antiplatelet within 7 days before the stroke onset. The primary outcome was SICH. Secondary outcomes were discharge modified Rankin Scale (mRS) score and in-hospital mortality.ResultsOf 1,715 patients treated with IV-TPA, 441 (25.7%) were on prestroke antiplatelet. Prestroke antiplatelet users versus non-users were more likely to be older, to have multiple vascular risk factors. Prestroke antiplatelet use was associated with an increased risk of SICH (5.9% vs. 3.0%; adjusted odds ratio [OR] 1.79 [1.05-3.04]). However, at discharge, the two groups did not differ in mRS distribution (adjusted OR 0.90 [0.72-1.14]), mRS 0-1 outcome (34.2% vs. 33.7%; adjusted OR 1.27 [0.94-1.72), mRS 0-2 outcome (52.4% vs. 52.9%; adjusted OR 1.21 [0.90-1.63]), and in-hospital mortality (6.1% vs. 4.2%; adjusted OR 1.19 [0.71-2.01]).ConclusionsDespite an increased risk of SICH, prestroke antiplatelet users compared to non-users had comparable functional outcomes and in-hospital mortality with IV-TPA therapy. Our results support the use of IV-TPA in eligible patients taking antiplatelet therapy before their stroke onset.

α2-Antiplasmin: New Insights and Opportunities for Ischemic Stroke.

Thrombotic vascular occlusion is the leading cause of ischemic stroke. High blood levels of α2-antiplasmin (a2AP), an ultrafast, covalent inhibitor of plasmin, have been linked in humans to increased risk of ischemic stroke and failure of tissue plasminogen activator (tPA) therapy. Consistent with these observations, a2AP neutralizes the therapeutic benefit of tPA therapy in experimental stroke. In addition, a2AP has deleterious, dose-related effects on ischemic brain injury in the absence of therapy. Experimental therapeutic inactivation of a2AP markedly reduces microvascular thrombosis, ischemic brain injury, brain swelling, brain hemorrhage, and death after thromboembolic stroke. These data provide new insights into the critical importance of a2AP in the pathogenesis of ischemic brain injury and suggest that transiently inactivating a2AP may have therapeutic value in ischemic stroke.