Intra-arterial Tissue Plasminogen Activator Research Articles

Intra-arterial thrombolysis in a child with acute basilar artery occlusion

We report a case of a child who suffered a left hemisphere arterial ischemic stroke due to basilar artery occlusion. He was treated with intra-arterial recombinant tissue plasminogen activator at six and a half hours after the onset of hemiparesis. There were no complications and he showed rapid neurological and neuroimaging improvement. Where facilities allow rapid assessment atacombined adult andpediatricneurosciences facility, intra-arterialrecombinant tissueplasminogen activator should be considered, especially for posterior circulation thrombosis.

Management of perioperative microvascular thrombotic complications – The use of multiagent anticoagulation algorithm in 395 consecutive free flaps

Thrombotic complications remain a major barrier to successful microsurgical reconstruction, but their effective management remains controversial. A retrospective review of 395 consecutive microvascular transfers was performed with the focus on treatment of thrombotic complications utilizing an algorithm, which employed multiagent anticoagulation. Three-hundred-ninety-five free flaps were performed in 255 patients for breast (n = 316), head and neck (n = 57), extremity (n = 16), trunk (n = 3), and pelvis (n = 3) defects that were oncologic in 95.2% and irradiated in 33.4% of cases. Patients with a hypercoagulable history (8 of 9) and intraoperative thrombosis (16 of 16) were anticoagulated without developing postoperative thrombotic events. The hematoma exploration rate among the patients anticoagulated during the initial free flap procedure was 27%. Twenty four (9.4%) patient were returned to the operating room postoperatively for threatened free flaps: 6 had non-microvascular issues and 18 (7.1%) patients underwent microsurgical explorations. Fourteen (5.5%) patients had 15 postoperative free flap thrombotic events in 14 free flaps, of which 12 flaps were successfully salvaged with a combination of flap intra-arterial (n = 15), subcutaneous/intramuscular (n = 6), and intravenous (n = 3) tissue plasminogen activator (tPA), microvascular explorations (n = 20), and therapeutic multiagent anticoagulation/antiplatelet therapy (n = 17); none had a hematoma of the reconstructed site. Two free flaps were lost to arterial thrombosis, with an overall microvascular salvage rate of 89% and a free flap success rate of 99.5%. Thrombophilia uncovered by microvascular procedures can be effectively treated with anticoagulation upon discovery and prevent postoperative free flap thrombotic events. High free flap salvage can be achieved with the early intervention combined with thrombolysis and multiagent anticoagulation and antiplatelet therapy.

Periprocedural Cost-Effectiveness Analysis of Mechanical Thrombectomy for Acute Ischemic Stroke in the Stent Retriever Era

Background: Early reperfusion is critical for favorable outcomes in acute ischemic stroke (AIS). Stent retrievers lead to faster and more complete reperfusion than previous technologies. Our aim is to compare the cost-effectiveness of stent retrievers to the previous mechanical thrombectomy devices. Methods: Retrospective review of endovascularly treated large-vessel AIS. Data from all consecutive patients who underwent thrombectomy from January 2012 through November 2012 were collected. Baseline characteristics, the total procedural cost, the rates of successful recanalization [modified thrombolysis in cerebral ischemia (mTICI) scores of 2b or 3], and the length of stay at the hospital were compared between the stent retriever (SR) and the non-stent retriever (NSR) groups. Results: After excluding the patients who underwent concomitant extracranial stenting (n = 22) or received intra-arterial tissue plasminogen activator only (n = 6), the entire cohort included 150 patients. The cost of the reperfusion procedure was significantly higher in the SR compared to the NSR group (USD 13,419 vs. 9,308, p <0.001). We were unable to demonstrate a statistically significant difference in the rates of mTICI 2b/3 reperfusion (81 vs. 74%, p = 0.337) or the length of stay (11.1 ± 9.1 vs. 12.8 ± 9.6 days, p = 0.260) amongst the SR and the NSR patients. Conclusion: The procedural costs of thrombectomy for AIS are increasing and account for the bulk of hospitalization reimbursement. The impact of these expenditures in the long-term sustainability of stroke centers deserves greater consideration. While it is likely that the SR technology results in higher rates of optimal reperfusion, better clinical outcomes, and shorter lengths of stay, larger studies are needed to prove its cost-effectiveness.

Predictors of Long-term Outcome after Intravenous or Intra-arterial Recombinant Tissue Plasminogen Activator Treatment in the Eastern Hungarian Thrombolysis Database

This prospective single-center study aimed to identify features determining long-term outcome after thrombolysis in a Central European stroke population. Between 1 January, 2004, and 31 December, 2010, 415 patients were treated with recombinant tissue plasminogen activator at the Department of Neurology, University of Debrecen. Stroke severity by the National Institute of Health Stroke Scale score (NIHSSS) and imaging findings by the Alberta Stroke Programme Early Computed Tomography score (ASPECTS) were evaluated on admission and 1 day later. The modified Rankin Scale (mRS) at 3 months and case fatality at 1 year were evaluated. Independent predictors of outcome were identified by multivariate testing. Data of 369 patients were analyzed. Median NIHSSS was 12 (interquartile range [IQR], 8-17) on admission and 10 (IQR, 5-16) at 24 hours. Arterial occlusion was found in 55%. Symptomatic intracerebral hemorrhage (SICH) was detected in 3.8%. Outcome was significantly worse, and SICH was more frequent in intra-arterially treated patients. At 3 months, one third of the patients were independent (mRS ≤ 2), and 23% were dead. At 1 year 2 of 3 patients were alive. Significant independent predictors of disability at 3 months were 24-hour NIHSSS, admission ASPECTS, admission glucose level, and treatment modality. Only the 24-hour NIHSSS was a significant predictor of case fatality at 1 year. Although short-term outcome was similar, the 3-month and 1-year outcomes were worse than data from previous reports. A more efficient health care program should be implemented after stroke to maintain the favorable effect of thrombolysis in the long term.

Waveform Recognition in Code Stroke Transcranial Doppler Studies

The Code Stroke designation was implemented in the 1990's to insert time urgency in treating stroke patients with intravenous or intra-arterial tissue plasminogen activator (t-PA). This drug can fragment the intracranial arterial thrombus before the advent of permanent brain damage (3 hours after symptom onset) in roughly 20% of Code Stroke patients. Fragmentation and resolution of intra-arterial thrombus is a dynamic process. Transcranial Doppler (TCD) is uniquely positioned to monitor these changes as they occur. Five unique TCD waveforms have been isolated that commonly occur during and after a stroke. A registered vascular sonographer should be able to rapidly obtain and recognize these waveforms.

Endovascular treatment for M2 occlusions in the era of stentrievers: a descriptive multicenter experience

BackgroundPatients with M2 middle cerebral artery (MCA) occlusions are not always considered for endovascular treatment.ObjectiveTo study outcomes in patients with M2 occlusion treated with endovascular procedures in the era of...

Hybrid approach in patients with recurrent brachial artery embolism: adjunctive tissue plasminogen activator infusion following embolectomy

Acute ischemia of an upper extremity occurs less frequently than vascular events of the leg and accounts for 15%-32% of all cases. Embolectomy provides prompt and effective treatment in the majority of cases. Recurrence of embolism and failed reperfusion can result in poor outcomes, even extremity loss. Adjunctive managements become important in this patient group. In this report, we present percutaneous intraarterial drip tissue plasminogen activator infusion to rescue the extremity in a patient with small cell lung cancer who experienced thromboembolism an additional six times following embolectomy.

Fibrinolytic agents for peripheral arterial occlusion

Peripheral arterial thrombolysis is used in the management of peripheral arterial ischaemia. Streptokinase was originally used but safety concerns led to a search for other agents. Urokinase and recombinant tissue plasminogen activator (rt-PA) have increasingly become established as first line agents for peripheral arterial thrombolysis. Potential advantages of these agents include improved safety, greater efficacy and a more rapid response. Recently drugs such as pro-urokinase, recombinant staphylokinase and alfimperase have been introduced. This is an update of a review first published in 2010. To determine which fibrinolytic agents are most effective in peripheral arterial ischaemia. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched March 2013) and CENTRAL (2013, Issue 3) for randomised controlled trials (RCTs) comparing fibrinolytic agents to treat peripheral arterial ischaemia. RCTs comparing fibrinolytic agents to treat peripheral arterial occlusion. Data were analysed for the outcomes vessel patency, time to lysis, limb salvage, amputation, death, complications including major haemorrhage, stroke, and distal embolization. Five RCTs involving a total of 687 participants with a range of clinical indications were included. No new studies were included in this update. In one three-pronged study, vessel patency was greater with intra-arterial recombinant tissue plasminogen activator (rt-PA) than with intra-arterial streptokinase (P < 0.04) or intravenous rt-PA (P < 0.01). In participants with peripheral arterial occlusion there was no statistically significant difference in limb salvage at 30 days with either urokinase or rt-PA, though this may reflect the small numbers in the studies. Incidences of haemorrhagic complications varied with fibrinolytic regime but there was no statistically significant difference between intra-arterial urokinase and intra-arterial rt-PA. In the three-pronged study intravenous rt-PA and intra-arterial streptokinase were associated with a significantly higher risk of haemorrhagic complications than with intra-arterial rt-PA (P < 0.05). There is some evidence to suggest that intra-arterial rt-PA is more effective than intra-arterial streptokinase or intravenous rt-PA in improving vessel patency in people with peripheral arterial occlusion. There was no evidence that rt-PA was more effective than urokinase for patients with peripheral arterial occlusion and some evidence that initial lysis may be more rapid with rt-PA, depending on the regime. Incidences of haemorrhagic complications were not statistically significantly greater with rt-PA than with other regimes. However, all of the findings come from small studies and a general paucity of results means that it is not possible to draw clear conclusions.

Intra-Arterial Tissue Plasminogen Activator for an Ischemic Stroke in a 21-Year-Old Hispanic Woman With Elevated Beta Human Chorionic Gonadotropin and Complex Clinical History

The following case report discusses a 21-year-old Hispanic woman who was brought to the emergency room for evaluation because of experiencing acute left-sided hemiparesis with anosognosia. Upon further assessment, the patient was found to have a positive blood test for methamphetamines, positive human chorionic gonadotropin for pregnancy, and a history of patent foramen ovale. Neurological examination of the patient revealed left hemiparesis, dysarthria, and homonymous hemianopsia of the left side with a National Institutes of Health Stroke Scale of 12. Given the patient's assessment and positive radiological findings of a clot located within the right M1 segmental branch of the middle cerebral artery territory through the use of computed tomography angiography, deployment of intra-arterial thrombolytics within 6 hours of symptom onset was utilized. The patient's clinical course was complicated by brain swelling requiring intubation. Return of neurological function was assessed with noninvasive and invasive neurological evaluation, which showed full cognitive and physical return of the functional baseline level at discharge.

E-070 Endovascular treatment in a paediatric patient with thrombus extending from right internal carotid artery to right middle cerebral artery

IntroductionPaediatric stroke leads to significant morbidity and mortality. Approximately10–25% of children with a stroke will die, up to 25% of children will have a recurrence, and approximately 66% will have...

Selecting Endovascular Treatment Strategy according to the Location of Intracranial Occlusion in Acute Stroke

Background: Selection of endovascular approaches for acute stroke patients remains unclear. The efficacy of intra-arterial therapy (IAT) has been demonstrated in the past. However, in the last years, the use of mechanical thrombectomy by retrievers (RET) is increasing at the expense of IAT. We aimed to compare several clinical outcomes between patients treated with IAT or RET. Methods: In a 6-year period, acute stroke patients (<8 h) with confirmed internal carotid artery (ICA) occlusion or middle cerebral artery (MCA) occlusion undergoing endovascular therapy were prospectively included in our database. Patients who underwent intra-arterial tissue plasminogen activator (tPA) ± microguidewire mechanical clot disruption (IAT group) were compared with those who underwent thrombectomy with the Solitaire® or Trevo® retrievers (RET group). Recanalization (REC) was considered if at the end of the endovascular procedure thrombolysis in cerebral infarction score was 2a-3. Dramatic clinical improvement (DCI) was defined as a decrease of ≥10 NIHSSS points from baseline to discharge or 7 days. Results: One hundred and eighty patients were included, 100 (55.6%) patients in the IAT group and 80 patients (44.4%) in the RET group. There were no differences in baseline characteristics (age, gender, risk factors profile, previous treatment with i.v. tPA, baseline NIHSS, extracranial ICA angioplasty and time to REC). Rates of REC, DCI and symptomatic intracranial hemorrhage were also similar between groups. Among patients with ICA occlusions (41 IAT, 34 RET), REC was significantly higher with RET (83.9 vs. 61%; p = 0.04).There was a trend towards a higher DCI rate in the RET group (32.3%) compared with the IAT group (14.6%; p = 0.06). According to MCA occlusions, there were no major differences in the main outcome variables. The number needed to treat to achieve one additional DCI with RET compared with IAT was 12 for MCA occlusions, and only 5 for ICA occlusions. Conclusions: Among acute stroke patients undergoing endovascular therapies, the benefits of RET over IAT are greater in ICA occlusions. Retrievers may be considered as the first therapeutic option in these patients.

Stentrievers versus other endovascular treatment methods for acute stroke: comparison of procedural results and their relationship to outcomes

Background and purposeThe use of stentrievers (ST) is rapidly growing due to several potential benefits over other available treatments. ST potentially restore flow before clot retrieval and reduce procedural time....

Intra-arterial tissue plasminogen activator and abciximab in patients with acute basilar artery occlusion

Acute basilar artery occlusion has a poor prognosis and best treatment has not been assessed yet; as for intra-arterial treatment, no "gold standard" exists. We evaluated a series of ten patients treated with intra-arterial combination of recombinant tissue plasminogen activator (rtPA) and abciximab. Partial/complete recanalisation was achieved in all patients and good outcome (1 month Modified Rankin Scale 0-2) in eight cases, while one patient had symptomatic intracranial haemorrhage and died. Such outcome appears significantly better if compared with the results of Basilar Artery International Cooperation Study, suggesting that intra-arterial administration of rtPA and abciximab may be a promising option in patients with acute basilar artery occlusion undergoing endovascular treatment.

Management of Acute Ischemic Stroke

Stroke is one of the most common causes of morbidity and mortality in hospitalized patients in the United States. A proper understanding of stroke mechanisms helps to guide specific case management. The only therapy approved by the US Food and Drug Administration for the management of acute ischemic stroke is initiation of intravenous recombinant tissue plasminogen activator within 3 hours of symptom onset. Other treatment options include intra-arterial recombinant tissue plasminogen activator, mechanical thrombectomy, clot retrieval, or a combination of these approaches. In this article, we provide an evidence-based review of the diagnostic approach for acute ischemic stroke, including recognizing common stroke mimics. We detail the initial medical management of acute stroke and the medical and surgical therapeutic interventions for patients who have sustained acute ischemic stroke.

Venous Thromboembolism in the Get With The Guidelines-Stroke Acute Ischemic Stroke Population: Incidence and Patterns of Prophylaxis

Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolus (PE), represents a serious complication in hospitalized ischemic stroke patients. This study examines the incidence of VTE and the patterns of VTE prophylaxis in acute ischemic stroke patients deemed appropriate forVTE prophylaxis (nonambulatory) in the Get With The Guidelines-Stroke (GWTG-S) study. We analyzed data from 149,916 patients who were admitted with acute ischemic stroke and enrolled in GWTG-S from 1259 U.S. hospitals. Patient variables and site characteristics were analyzed in relation to reported administration of VTE prophylaxis. The overall rate of VTE prophylaxis in the analysis cohort was 93% (139,476/149,916). The median site prophylaxis rate was 95%, and prophylaxis rates ranged from 17% (1 site) to 100% (101 sites). Factors associated with increased likelihood of VTE prophylaxis in the multivariable model included history of atrial fibrillation/flutter, receipt of intravenous or intra-arterial tissue plasminogen activator, and admission to an academic hospital. Increasing age, black race, and a history of peripheral vascular disease, diabetes, or stroke were associated with lower likelihood of prophylaxis. Patients receiving care in the Midwest were less likely to receive prophylaxis compared to other regions. Despite a high overall rate of VTE prophylaxis, VTE was found to occur in approximately 3% of GWTG-S patients. Reported rates of VTE prophylaxis differed among hospitals by region and hospital type, and among patients by age, race, and medical comorbidities.

A thromboembolic model for the efficacy and safety evaluation of combined mechanical and pharmacologic revascularization strategies

Background and purposeRecanalization strategies mediated by intra-arterial fibrinolytic therapy in combination with mechanical clot disruption may be a more effective treatment approach than either therapy used alone. There are few...

Sequence-specific MR Imaging Findings That Are Useful in Dating Ischemic Stroke

Patients may present to the hospital at various times after an ischemic stroke. Many present weeks after a neurologic deficit has occurred, as is often the case with elderly patients and those in a nursing home. The ability to determine the age of an ischemic stroke provides useful clinical information for the patient, his or her family, and the medical team. Many times, perfusion imaging is not performed, and pulse sequence-specific magnetic resonance (MR) imaging findings may help determine the age of the infarct. The findings seen at apparent diffusion coefficient mapping and diffusion-weighted, fluid-attenuated inversion recovery (FLAIR) and unenhanced and contrast material-enhanced T1- and T2-weighted gradient-echo and susceptibility-weighted MR imaging may help determine the relative age of a cerebral infarct. Strokes may be classified and dated as early hyperacute, late hyperacute, acute, subacute, or chronic. Recent data indicate that in many patients with restricted diffusion and no change on FLAIR images, it is more likely than was initially thought that the stroke is less than 6 hours old. The time window to administer intravenous tissue plasminogen activator is currently 4.5 hours from the time when the patient was last seen to be normal, and for anterior circulation strokes, the time window for administering intraarterial tissue plasminogen activator is 6 hours from when the patient was last seen to be normal. For this reason, accurate dating is important in patients with ischemic stroke.

Comparative Sensitivity of Computed Tomography vs. Magnetic Resonance Imaging for Detecting Acute Posterior Fossa Infarct

BackgroundPosterior fossa strokes, particularly those related to basilar occlusion, pose a high risk for progression and poor neurological outcomes. The clinical history and examination are often not adequately sensitive or specific for detection. Study ObjectivesBecause this population stands to benefit from acute interventions such as intravenous and intra-arterial tissue plasminogen activator, mechanical thrombectomy, and intensive monitoring for neurologic deterioration, this study examined the sensitivity of non-contrast head computed tomography (NCCT) for diagnosing posterior fossa strokes in the emergency department. MethodsThis study analyzed a prospectively collected database of acute ischemic stroke patients who underwent head NCCT within 30h of symptom onset and who were subsequently found to have a posterior fossa infarct on brain magnetic resonance imaging (MRI) performed within 6h of the NCCT. ResultsThere were 67 patients identified who had restricted diffusion on MRI in the posterior fossa. The National Institutes of Health Stroke Scale (NIHSS) scores ranged from 0 to 36, median 3. Only 28 patients had evidence of infarction on the initial NCCT scan. The timing of NCCT scans ranged from 1.2 to 28.9h after symptom onset. The sensitivity of NCCT was 41.8% (95% confidence interval 30.1–54.4). The longest period of time between symptom onset and a negative NCCT with a subsequent positive diffusion-weighted imaging MRI was 26.7h. ConclusionsHead NCCT imaging is frequently insensitive for detecting posterior fossa infarction. Temporal evolution of strokes in this distribution, coupled with beam-hardening artifact, may contribute to this limitation. When a posterior fossa stroke is suspected and the NCCT is non-diagnostic, MRI is the preferred imaging modality to exclude posterior fossa infarction.

Mechanical embolectomy for treatment of large vessel acute ischemic stroke in children

Background and purposeThe three largest adult stroke trials investigating mechanical embolectomy retrieval devices in acute stroke (the Merci, Multi Merci and Penumbra Pivotal Stroke Trials) excluded children. There is a...

Abstract 2825: History of Cancer Predicts Mortality After Acute Endovascular Treatment for Ischemic Stroke

Introduction: Endovascular treatment is an emerging therapy for acute ischemic stroke. There is no clear consensus about how best to select patients that may benefit from intervention. We conducted an exploratory analysis of clinical risk factors to predict mortality after endovascular intervention in order to better understand how to improve outcomes for patients with acute ischemic stroke. Methods: We identified consecutive series of patients treated with endovascular therapy for acute ischemic stroke at two academic hospitals between 2005 to 2010. Key clinical data elements and clinical outcomes at the time of discharge were abstracted from medical records. We evaluated univariate and multivariable associations using logistic regression and compared mean NIH Stroke Scale between those with and without a history of cancer using the t-test. Results: We identified 88 patients who received endovascular intervention with intra-arterial tissue plasminogen activator (t-PA) and/or mechanical thrombectomy. The mean age of the cohort was 68.2 (SD 16.6) and 44 (55%) were female. A total of 23 (26.1%) patients died during the index hospitalization or were discharged to hospice care. A history of cancer was documented in 20 (22.7%) patients. A history of cancer was associated with a 3.2-fold (95% CI 1.1-9.1) higher odds of mortality. This association persisted after adjusting for age greater than 80 years and hypertension (OR of 4.0, 95% CI 1.3-12). The average NIH Stroke Scale was 15.6 in those with cancer compared to 14.6 without (p=0.53). A history of cancer was not associated with parenchymal hemorrhagic transformation (OR 1.2, 95% CI 0.3-4.9), IV tPA (OR 0.5, 95% CI 0.1-2.3), a TIMI score of 2b or 3 (OR 0.5, 95% CI 0.2-1.3), or an internal carotid artery occlusion (OR 1.7, 95% CI 0.5-5.1). Conclusions: In an exploratory analysis of consecutive patients with acute ischemic stroke treated with endovascular therapy, a history of cancer was strongly associated with significantly increased odds of mortality. One possible explanation could be that patients with cancer may have earlier withdrawal of care but the reasons for this observed association are unclear. Further investigation is necessary to verify and explain the reasons for this observation in order to improve outcomes for acute ischemic stroke patients.