Urokinase In Patients Research Articles

Analysis of predictors of hemorrhagic transformation after reperfusion therapy with recombinant tissue plasminogen activator in patients with acute ischemic stroke: a single-center experience

BackgroundHemorrhagic transformation (HT) is a serious complication of thrombolytic therapy for acute ischemic stroke, limiting its indications and affecting treatment plans and clinical prognosis. Identifying risk factors for HT could help improve the risk–benefit ratio of thrombolytic therapy. We aimed to analyze the predictors of HT after reperfusion therapy with recombinant tissue plasminogen activator (rTPA) in patients with acute ischemic stroke. This study included 115 patients who received rTPA. All patients underwent history taking, clinical examination, neurological examination including Glasgow Coma Scale and National Institutes of Health Stroke Scale scores (NIHSS), radiological investigation, and cardiac investigation. Patients were followed up strictly every 2 h for 1st 24 h then for two weeks clinically using the NIHSS and radiologically using CT or MRI to detect HT.ResultsPatients with HT represented 21.7% of all patients receiving rTPA, while symptomatic intracranial hemorrhage (sICH) represented 6.9%. Patients with HT had significantly higher blood pressure, respiratory rate, atrial fibrillation rate, NIHSS score, INR, prothrombin time, neutrophil-to-lymphocyte ratio (NLR), and lower platelet count, LDL level, higher Fazekas score, lower ASPECT score, and prolonged onset-to-needle time.ConclusionPredicting HT in acute ischemic stroke patients is crucial for optimizing management and potentially improving outcomes. In our study, six predictors were associated with HT: higher respiratory rate, higher atrial fibrillation rate, higher NLR, lower LDL level, higher Fazekas score, lower ASPECT score, and onset-to-needle time greater than 180 min.

Comparison of Effectiveness and Safety of Low-Dose Versus Standard-Dose Intravenous Recombinant Tissue Plasminogen Activator in Patients With Acute Ischemic Stroke: A Meta-Analysis.

The aim of the present meta-analysis is to compare the efficacy and safety of low-dose and standard-doserecombinant tissue plasminogen activators (r-tPA) in patients with acute ischemic stroke. The present meta-analysis was conducted according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE)guidelines. We conducted a systematic search in PubMed, Embase, and the Cochrane Library to identify studies published between January 1, 2010, and January 31, 2023, using the following terms: "stroke," "alteplase," "doses," "efficacy," "tissue plasminogen activator," "r-tPA," and "safety."Primary efficacyoutcomes included favorable outcomes (Modified Rankin Scale scores of 0-2), while secondary efficacy outcome was all-cause mortality at 90 days. Safety outcomes included asymptomatic intracerebral hemorrhage (ICH)and symptomatic ICH assessed using the National Institute of Neurological Disorders and Stroke (NINDS) study and the Safe Implementation of Thrombolysis in Stroke-Monitoring (SITS-MOST) study. We also compared parenchymal hematomas as safety outcome between the two groups defined by the authors themselves in their research.A totalof 16 studies were included in the present meta-analysis. The meta-analysis did not report any significant difference between low-dose and standard-dose r-tPA in terms of mortality, symptomatic intracranial hemorrhage (SICH), asymptomatic ICH, and parenchymal hematomas. However, the favorable outcome was significantly greater in patients receiving a standard dose of r-tPA.

Repeated Intravenous Thrombolytic Treatment Experience with Tissue Plasminogen Activator In Patients with Acute Ischemic Stroke: Case Series

Repeated Intravenous Thrombolytic Treatment Experience with Tissue Plasminogen Activator In Patients with Acute Ischemic Stroke: Case Series

Intrapleural Instillation of Sodium Bicarbonate versus Urokinase in Management of Complicated Pleural Effusion: A Comparative Cohort Study.

The main target is evacuation; however, with evidence about the value of intrapleural instillation of different fibrinolytic agents still under evaluation, our aim was comparing the effectiveness and safety of intrapleural instillation of sodium bicarbonate (NaHCO3) in comparison with urokinase in patients with infected pleural effusion. Our prospective cohort study included 40 patients with complicated empyema; the diagnosis was based on analysis of aspirated fluid in association with radiological and bacteriological culture. The patients were subjected to instillation of two different fibrinolytic agents; the first one was NaHCO3, the second was urokinase. The commonest underlying chest infection that was visualized by CT was pneumonia 70%. Nearly half of cases had community-acquired infection (45%), and more than half of them (55%) had anaerobic infection, and only five cases had TB pleural effusion based on ADA-positive, tuberculin skin test in addition to Abram's needles closed biopsy. The rate of repeated therapeutic thoracentesis success in each group was 85%; 80% in NaHCO3 group, and 90% in urokinase group, both of them was significantly equal, P=0.37. Moreover, the frequency of complications in all patients was less than 13%, hence hemothorax and iatrogenic pneumothorax was 12.5%, and only 10% of cases were admitted in ICU after the maneuver, with insignificant difference in between the groups. However, looking at the smaller rate of RTT failure of NaHCO3 or urokinase, the logistic regression model showed that RTT-NaHCO3 was insignificantly related to failure in both unadjusted and adjusted models, P=0.37 and 0.32, respectively, and only smoking habits increase the likelihood of failure 9-fold (OR=8.9, P=0.04) with respect to age, sex, and treatment methods. The efficacy of repeated therapeutic thoracentesis (RTT) with intrapleural instillation of NaHCO3 was effective and safe, the same as urokinase, with consideration that NaHCO3 was much more available and affordable than urokinase.

Role of low-dose tissue plasminogen activator in patients with refractory hypoxia due to presumed microthrombi in pulmonary vasculature in coronavirus disease 2019: A case series and review of the literature.

Severe hypoxia due to coronavirus disease 2019 (COVID-19) is challenging in the intensive care unit (ICU). It is often unresponsive to mechanical ventilation at high positive end-expiratory pressure and the fraction of inspired oxygen combination. The cause of such worsening hypoxia may be microvascular thrombosis in the pulmonary vascular system because of the procoagulant nature of COVID-19 infection. Confirming the diagnosis with computed tomographic pulmonary angiography is not always possible, as the patients are too sick to be shifted. Tissue plasminogen activator (tPA) is recommended for pulmonary thromboembolism with hypotension and worsening hypoxia, as confirmed by computed tomography pulmonary angiography. However, its role in worsening hypoxia because of presumed microthrombi in the pulmonary vasculature in COVID-19 is unclear. We present six cases from our ICU where we used low-dose tPA in COVID-19 refractory hypoxia with presumed microthrombi in the pulmonary vasculature (oligemic lung field, refractory hypoxia, increased D dimer, electrocardiographic features of pulmonary embolism, and right ventricular strain on echocardiography). Oxygenation improved within 6 h and was maintained for up to 48 h in all patients. Therefore, there is a possible role of microthrombi in the mechanism of hypoxia in this setting. An early decision to start low-dose tPA may improve the outcome. However, all patients finally succumbed to sepsis and multiorgan failure later in their course. A systematic review of the literature has also been performed on the mechanism of thrombosis and the use of tPA in hypoxia due to COVID-19.

Thrombotic Occlusion in Patients With Acute Ischemic Stroke

Currently, reperfusion therapy is the main method of treating patients with ischemic stroke (IS). The safety and efficacy of systemic thrombolytic therapy with a recombinant tissue plasminogen activator in patients with IS within 3 hours, and then 4.5 hours after the onset of symptoms of the disease was demonstrated in the NINDS (1995) and ECASS III (2008) studies. In 2018, based on the results of five studies, clear indications were formulated for performing thrombectomy (TE) in patients with IS, which involve the detection of thrombosis of a large stroke-associated artery. Given the continuous growth in the number of the adult population, which constitutes the bulk of patients with IS, information on the prevalence of patients with thrombotic occlusion of cerebral arteries, who are potential candidates for TE, may be important for regional vascular centers.Aim of study. To describe IS patients admitted within the 6-hour “therapeutic window”.Materials and methods. The study included 145 patients with cerebral IS who were admitted within the first 6 hours after the onset of symptoms of the disease. All patients underwent computed tomographic (CT) angiography in order to verify the occlusion of the cerebral artery.Results. In our study, a correlation was established between the NIHSS severity of IS and the likelihood of verification of stroke-related artery thrombosis by CT angiography, but in 32.6% of patients with severe stroke (NIHSS at least score 14), no thrombotic occlusion was detected, and in 13% of patients with a clinic of mild acute cerebrovascular accident (NIHSS no more than 6), on the contrary, thrombotic occlusion was detected. Mortality in patients with verified thrombotic occlusion of the cerebral artery was higher than in patients without it (38% versus 10.5%, p<0.001). Such a significant difference in the mortality rate was due to the initially more severe stroke (NIHSS at admission 17 [10; 23] versus 5 [2; 10], p><0.001) in patients with thrombotic occlusion of a stroke-related artery, as well as a higher incidence of severe swallowing disorders (30% versus 9.5%, p ><0.002), which are a risk factor for pneumonia, as well as a higher frequency of such a comorbid background as chronic kidney disease and atrial fibrillation (30% versus 13.7%, p=0.018% and 58% versus 29.5%, p=0.001, respectively). CONCLUSION 1. Thrombosis of the cerebral stroke-associated artery was detected in 34.5% of patients with ischemic stroke who were admitted within the first 6 hours from the onset of the disease. 2. The main reason for the failure to perform thrombectomy in patients with ischemic stroke admitted within the 6-hour therapeutic window is the lack of verification of stroke-related artery thrombosis using computed tomographic angiography. Due to thrombosis at a different location (other than thrombosis of the internal carotid artery and / or M1 segment of the middle cerebral artery), 10% of patients with verified thrombosis did not meet the currently existing selection criteria for thrombectomy. Keywords: ischemic stroke, reperfusion therapy, cerebral artery thrombosis, cryptogenic stroke>˂0.001). Such a significant difference in the mortality rate was due to the initially more severe stroke (NIHSS at admission 17 [10; 23] versus 5 [2; 10], p˂0.001) in patients with thrombotic occlusion of a stroke-related artery, as well as a higher incidence of severe swallowing disorders (30% versus 9.5%, p˂0.002), which are a risk factor for pneumonia, as well as a higher frequency of such a comorbid background as chronic kidney disease and atrial fibrillation (30% versus 13.7%, p=0.018% and 58% versus 29.5%, p=0.001, respectively).Conclusion. 1. Thrombosis of the cerebral stroke-associated artery was detected in 34.5% of patients with ischemic stroke who were admitted within the first 6 hours from the onset of the disease. 2. The main reason for the failure to perform thrombectomy in patients with ischemic stroke admitted within the 6-hour therapeutic window is the lack of verification of stroke-related artery thrombosis using computed tomographic angiography. Due to thrombosis at a different location (other than thrombosis of the internal carotid artery and / or M1 segment of the middle cerebral artery), 10% of patients with verified thrombosis did not meet the currently existing selection criteria for thrombectomy.

Intravenous thrombolysis with alteplase in the treatment of acute cerebral infarction.

Objectives:To compare the efficacy and safety of intravenous thrombolysis with alteplase and intravenous thrombolysis with urokinase for patients with acute cerebral infarction.Methods:This prospective study included 140 patients with acute cerebral infarction who were admitted to our hospital between June 2018 and June 2019. They were randomly divided into two groups. The control group (70 cases) was treated with urokinase intravenous thrombolysis, and the observation group (70 cases) was given alteplase intravenous thrombolytic therapy. The treatment efficacy and safety of the two groups were compared.Results:The total effective rate of the observation group was 95.7%, and that of the control group was 78.6%, i.e., the total effective rate of the observation group was significantly superior to the that of the control group (P < 0.05). After treatment, the observation group had significantly lower National Institutes of Health Stroke Scale (NIHSS) score and significantly higher mini-mental state examination (MMSE) score than the control group; the difference was statistically significant (P<0.05). After treatment, the levels of inflammatory factors of both groups significantly decreased compared to before treatment, and the decrease in the observation group was larger than that in the control group (P<0.05). The levels of serum homocysteine (Hcy) and monocyte chemoattractant protein-1 (MCP-1) in the observation group were significantly lower than those in the control group after treatment, and the differences were statistically significant (P<0.05). The incidence of hemorrhagic adverse reaction in the observation group was lower than that in the control group (P<0.05).Conclusion:In the treatment of acute cerebral infarction, ccompared with urokinase, alteplase can further relieve cognitive impairment and promote the recovery of nerve function through inhibiting levels of inflammatory factors and levels of serum Hcy and MCP-1.

THE ROLE OF THE UROKINASE SYSTEM IN LYMPHOGENOUS METASTASIS OF COLORECTAL CANCER

The aim of this work was to study the role and relationship of the levels of the components of the urokinase system with lymphogenous metastasis in patients with colorectal cancer.Materials and methods: the study was carried out on the basis of the Medical Scientific and Educational Center of the Moscow State University named after M.V. Lomonosov from 2019 to 2021. The study included healthy donors (control group) and patients with a verified diagnosis of stage I-III colorectal cancer in accordance with the inclusion criteria; all patients underwent surgical resection of the primary tumor with lymphadenectomy of the appropriate level. All patients underwent determination of the level of uPA and uPAR in blood serum before surgery. We also analyzed the clinical and demographic data of the patients, as well as the pathomorphological characteristics of the tumor.Results. The study included 7 healthy donors and 49 patients with stage I-III colorectal cancer. The average level of serum urokinase in the control group was 2.7±1.04 ng / ml, in the study group – 4, 15±1.9 ng / ml (p = 0.071), the level of the urokinase receptor in the control and study groups was 1.36 ±0.8 ng / ml vs 3.22±2.06 ng / ml (p = 0.05). The average level of serum urokinase in patients without and with lesions of lymph nodes was 3.4±1.4 ng / ml and 4.4±2.3 ng / ml (p = 0.068).Conclusion. There is a tendency to an increase in the level of components of the urokinase system in the peripheral blood in patients with colon neoplasms in the preoperative period, depending on the presence of metastatic lesions of regional lymph nodes, which indicates the need for further research in this area.

Surgical safety criteria for burr hole surgery with urokinase in patients with acute subdural hematoma: Retrospective comparison between burr hole surgery and craniotomy

Background: Acute subdural hematoma (ASDH) is a common disease and craniotomy is the first choice for removing hematoma. However, patients for whom craniotomy or general anesthesia is contraindicated are increasing due to population aging. In our department, we perform burr hole surgery under local anesthesia with urokinase administration for such patients. We compared the patient background and outcomes between burr hole surgery and craniotomy to investigate the surgical safety criteria for burr hole surgery.Methods: We reviewed 24 patients who underwent burr hole surgery and 33 patients who underwent craniotomy between January 2010 and April 2020 retrospectively.Results: The median age of the burr hole surgery group was older (P = 0.01) and they had multiple pre-existing conditions. Compared with the craniotomy group, neurological deficits and CT findings were minor in the burr hole surgery group, whereas the maximum hematoma thickness was not significantly different. The hematoma was excreted after a total of 54,000 IU of urokinase was administered for a median of 3 days. The Glasgow Coma Scale score improved in all patients in the burr hole surgery group and there were no deaths. Age, especially over 65 y.o., (OR 1.16, 95% CI 1.04–1.30) and the absence of basal cistern disappearance (OR 0.04, 95% CI 0.004–0.39) were significant factors.Conclusion: Burr hole surgery was performed safely in all patients based on the age, especially older than 65 y.o., and the absence of basal cistern disappearance. ASDH in the elderly is increasing and less invasive burr hole surgery with urokinase is suitable for the super-aging society.

Clinical safety and outcome of recombinant tissue plasminogen activator in patients with stroke attributable to small artery occlusion: A protocol for systematic review and meta-analysis.

Background:Recent observations raised concern that the intravenous recombinant tissue plasminogen activator (rt-PA) may result in damage to stroke patients caused by small artery occlusion (SAO). Thus, we perform a protocol for meta-analysis to investigate the efficacy and safety of intravenous thrombolysis with rt-PA in SAO-patients.Methods:The search-style electronic libraries, including Pubmed, Embase, the Cochrane Library, Web of Science, Wanfang Data, VIP Chinese Journals, and China Biomedical Literature Service System are used for document retrieval in June 2021 with no restrictions on language. The risk of bias in include articles will be assessed using the Cochrane Risk of Bias Tool. We perform the meta-analysis by Stata version 10.0 software and calculated the statistics using the inverse variance statistical method. Binary outcomes are presented as Mantel-Haenszel-style risk ratios with 95% confidence interval. Continuous outcomes are reported as mean differences.Results:The results of the article will be shown in a peer-reviewed journal.Conclusion:Intravenous rt-PA may be effective and safe in SAO-patients.

Barriers to Receiving Tissue Plasminogen Activator in Patients with Ischemic Stroke

Background: Cerebrovascular diseases are the second common cause of mortality worldwide. The onset of reperfusion in the first 3-4.5 hours is a predictive factor of treatment. Objective: The present study investigated barriers to receiving tissue plasminogen activator in patients with ischemic stroke. Methods: This cross-sectional study examined 191 patients with first-ever stroke referring to the emergency department of the Persian Gulf Martyrs Hospital of Bushehr City, Iran, in 2016. One checklist was completed which included demographic data, history of diseases, knowledge of stroke symptoms, and intervals regarding the onset of symptoms to informing emergency, informing emergency on arrival at the emergency department of the hospital, and making the diagnosis for the patients. The obtained data were analyzed in SPSS v. 19. Results: Mean±SD age of the patients was 65.92±12.48 years. The majority of patients under investigation (55.5%) were female, 63.4% were married, 56% were illiterate and 72.3% resided in other districts of Bushehr province. Mean duration between onset of symptoms and arrival at emergency department, onset of symptoms and call the emergency service, time of arrival at emergency department to perform brain Computer Tomography (CT) scan and also to be counseled by a neurologist were 699.66, 195.51, 45.11 and 423.62 minutes, respectively. Finally 14.6 percent of patients were qualified to be treated with tPA. Conclusion: The main barrier to timely therapy is a delay in golden time. Therefore, public education to promote public awareness could be of great benefit in reducing the referral delay time.

Fibrinolysis with Lower Dose Urokinase in Patients with Complicated Parapneumonic Effusion.

BackgroundIntrapleural urokinase is one of the most widely used fibrinolytic agents in the treatment of complicated parapneumonic effusion (CPPE). However, little research has been performed on the optimal urokinase dosage. The aim of this study was to evaluate the treatment efficacy of half dose urokinase compared with conventional dose urokinase.MethodsWe retrospectively enrolled 92 patients with CPPE or empyema who underwent intrapleural urokinase treatment at two tertiary hospitals. Patients received antibiotics, chest tube drainage, and other treatments as part of routine care. The primary outcome was the treatment success rate in the half dose urokinase group (50,000 IU daily for maximal 6 days) and the conventional dose urokinase group (100,000 IU daily). Treatment success was defined as clinical and radiological improvements without surgical treatment or re-admission within one month.ResultsForty-four patients received half dose urokinase, whereas 48 patients were treated with conventional dose urokinase. Both groups were relatively well matched at baseline, excluding higher serum white blood cell count and higher empyema prevalence in the half dose urokinase group. The treatment success rate was not different between the two groups (p=0.048). There were no differences in the rate of in-hospital death and surgical treatment, hospitalization duration, and indwelling catheter duration. In the multivariate analysis, urokinase dose was not a predictor of treatment success.ConclusionHalf dose intrapleural urokinase is equally effective conventional dose urokinase in treating patients with CPPE or empyema.

Clinical safety and efficacy of thrombolytic therapy with low-dose prolonged infusion of tissue type plasminogen activator in patients with intermediate-high risk pulmonary embolism.

: The patients with intermediate-high risk pulmonary embolism who have acute right ventricular (RV) dysfunction and myocardial injury without overt hemodynamic compromise may be candidates for thrombolytic therapy. Alternative low-dose thrombolytic therapy strategies with prolonged infusion may further decrease the complication rates as its efficacy and safety have been previously proven in the management of prosthetic valve thrombosis. In this study, we aimed to investigate the clinical outcomes of low-dose prolonged thrombolytic therapy regimen in intermediate-high risk pulmonary embolism patients. This study enrolled 16 retrospectively evaluated patients (female 9, mean age: 70.9 ± 13.5 years) with the diagnosis of acute pulmonary embolism who were treated with low-dose and slow-infusion of tissue-type plasminogen activator (t-PA). All patients underwent transthoracic echocardiography and computed tomography scan for assessment of thrombolytic therapy success. Low-dose prolonged thrombolytic therapy was successful in all patients. The mean t-PA dose used was 48.4 ± 6.3 mg. There was residual segmental thrombus in nine (56.3%) patients after thrombolytic therapy. The arterial oxygen saturation and tricuspid annular plane systolic excursion increased after thrombolytic therapy whereas heart rate, RV to left ventricular (LV) ratio, systolic pulmonary artery pressure, and the frequencies of hypotension and tachypnea significantly decreased. There was no cerebrovascular accident or major bleeding requiring transfusion. There were two minor bleedings (12.5%) including hemoptysis and epistaxis. Thrombolytic therapy in these intermediate-high risk pulmonary embolism patients was associated with excellent clinical outcomes and survival to discharge (100%) without any 60-day mortality. Prolonged thrombolytic therapy regimen with low-dose and slow-infusion of t-PA may be associated with lower complication rates without comprimising effectiveness in patients with acute intermediate-high risk pulmonary embolism.

Thrombolytic treatment of prosthetic valve thrombosis: a study using Urokinase

ObjectiveWe analysed the efficacy and safety of thrombolytic therapy with urokinase in patients with prosthetic valve thrombosis.MethodsTwenty-three patients with valve thrombosis received thrombolytic treatment using urokinase. First, a 250,000 IU intravenous bolus injection was administered as a loading dose, followed by intravenous infusion of 100,000 IU/h for 10 h and anticoagulation with low molecular weight heparin every day. The maximum treatment time was 5 days, i.e., until the transvalvular pressure gradient was normal or close to normal. Transthoracic echocardiography (TTE) was used every 12 h to monitor whether the thrombus was reduced and whether there was haemodynamic improvement. Routine blood tests, the prothrombin time (PT), international normalized ratio (INR) and complications were observed every day.ResultsSixteen (69.6%) patients were successfully treated with thrombolytic therapy: 2/2 (100%) aortic valves and 14/21 (66.7%) mitral valves. The partial success rate of this study was 13.0% (3/23). Four patients did not show any improvement in haemodynamics. Two cases had slight urine haemorrhage. One patient died of severe cerebral haemorrhage and shock. The overall mortality was 13.0% (3/23), including two patients who died after subsequent surgery.ConclusionUrokinase is more convenient and successful in the treatment of PVT. More experience may make TT the optimal treatment for PVT, especially in high-risk surgical situations.

Re-examining the exclusion criterion of early recurrent ischemic stroke in intravenous thrombolysis: A meta-analysis

BackgroundCurrent guidelines preclude the administration of intravenous tissue plasminogen activator in patients with early recurrent stroke (prior ischemic stroke within three months). ObjectivesThis is a meta-analysis that aimed to determine the safety and efficacy of thrombolysis in patients with early recurrent stroke. Summary of reviewPubmed, Cochrane, Scopus, Embase and Clinicaltrials.gov were searched for studies comparing the outcomes of acute ischemic stroke patients undergoing intravenous thrombolysis between those with early recurrent stroke and those without. Random-effects meta-analysis was used to evaluate the outcomes in terms of symptomatic intracranial hemorrhage, mortality and good functional outcomes at 3 months (modified Rankin Score ≤ 2). Three retrospective cohort studies with a total of 48,459 thrombolysed patients (824 with early recurrent stroke and 47,635 without early recurrent stroke) were included in the meta-analysis. There was no significant difference between thrombolysed patients with early recurrent stroke and those without in terms of symptomatic intracranial hemorrhage (Odds Ratio [OR] 1.39, 95% Confidence Interval [CI] 0.75–2.58), mortality (OR 1.36, 95% CI 0.60–3.09) and good functional outcomes at 3 months (OR 0.74, 95% CI 0.47–1.16). ConclusionsPatients who received thrombolysis despite early recurrent stroke were not found to be at an increased risk of adverse outcomes compared to patients without early recurrent stroke. Our meta-analysis suggests that there is insufficient evidence to substantiate excluding patients with early recurrent stroke from receiving thrombolysis. Further studies to re-examine early recurrent stroke as an exclusion criterion for receiving thrombolysis are warranted.

P.645 Immune cell-type specific methylation of tissue-type plasminogen activator in patients receiving electroconvulsive therapy

P.645 Immune cell-type specific methylation of tissue-type plasminogen activator in patients receiving electroconvulsive therapy

Thrombolysis with tissue plasminogen activator in patients with acute pulmonary embolisms in the real world: from the COMMAND VTE registry.

There is still uncertainty about the optimal usage of thrombolysis for acute pulmonary embolisms (PEs), leading to a widely varying usage in the real world. The COMMAND VTE Registry is a multicenter retrospective registry enrolling consecutive patients with acute symptomatic venous thromboembolisms (VTEs) in Japan. The present study population consisted of 1549 patients with PEs treated with tissue plasminogen activator (t-PA) thrombolysis (N = 180, 12%) or without thrombolysis (N = 1369). Thrombolysis with t-PA was implemented in 33% of patients with severe PEs, and 9.2% of patients with mild PEs with a wide variation across the participating centers. Patients with t-PA thrombolysis were younger, and less frequently had active cancer, history of major bleeding, and anemia. At 30days, t-PA thrombolysis as compared to no thrombolysis was associated with similar mortality rates (5.0% vs. 6.9%, P = 0.33), but a lower adjusted mortality risk (OR 0.41; 95% CI 0.18-0.90, P = 0.03), while it was associated with a trend for higher rates of major bleeding (5.6% vs. 2.9%, P = 0.06) and a significantly higher adjusted risk for major bleeding (OR 2.39; 95% CI 1.06-5.36, P = 0.03). In patients with severe PEs, the mortality rates at 30days were significantly lower in the t-PA thrombolysis group than no thrombolysis group (15% vs. 37%, P = 0.006). In the present real-world VTE registry in Japan, t-PA thrombolysis was not infrequently implemented, not only in patients with severe PEs, but also in patients with mild PEs. A substantial mortality risk reduction might be suggested with t-PA thrombolysis in patients with severe PEs.

Intravenous thrombolysis and mechanical thrombectomy in patients with minor or rapidly improving neurological deficits.

A substantial proportion of patients with ischemic stroke present with mild neurological deficits ('Stroke with mild symptoms,' SMS). Treating these patients with thrombolysis or with thrombectomy is controversial and clinical practice is different. We will highlight the importance of these treatment decisions by reviewing the recent advances in this area. Intravenous thrombolysis with recombinant tissue plasminogen activator in patients with SMS showed a significant reduction in functional disability after 3 months. Treatment with tenecteplase seems to be a pharmacologically superior and possibly safer thrombolytic agent making it ideal for use in this patient group. Imaging criteria to select the profiting patients are evolving. Thrombectomy in patients with a large vessel occlusion and minor deficits are showing promising results in cohort studies so far, however, randomized controlled trials are lacking. Patients with acute ischemic stroke and minor or rapidly improving symptoms should be carefully treated the same way as more severe strokes are treated as neurological deterioration is not infrequent. Nevertheless, treatment decisions should be individualized dependent on clinical and radiological features.

Analysis of the factors limiting reperfusion therapy in patients with ischemic strokes

Introduction. Systemic thrombolytic therapy with recombinant tissue plasminogen activator is the only reperfusion method available to most primary vascular units which allows significantly improving the functional prognosis of patients with ischemic stroke. Objective. To analyze the main determinants limiting reperfusion therapy administration in a subsidized region with demographic aging of the population, and to develop and scientifically justify the ways of their elimination. Materials and methods. We analyzed the data of the ambulance station in Smolensk electronic archive accounting for 17,143 phone requests for medical aid for patients with strokes, the data from the annual report of the neurological department for patients with acute cerebrovascular accident of the Clinical emergency care hospital, and 200 clinical records of patients diagnosed with acute stroke that were delivered to the in-patient facility by emergency medical service (EMS) teams in the period of the therapeutic window and who did not receive reperfusion therapy. The operative work of the dispatcher service, the efficiency of the mobile teams work, the structure of time losses during the call service, and the distribution of patients by the time period before the admission to a hospital depending on the way of admission and the remoteness of the zone of responsibility from the primary vascular surgery department were assessed. Results. It was found that statistically significant differences in time period before admission to a hospital of patients with ischemic strokes depend on the admission way and, in the case of arrival by the EMC, do not depend on the distance of the delivery area. The low efficiency of the mobile teams is due to the imperfection of call processing by dispatchers and the lack of a systematic approach and a single algorithm aimed for diagnosing and providing emergency assistance to the medical personnel of EMS teams. The main non-regulating factors for abandoning systemic administration of the recombinant tissue plasminogen activator in patients with ischemic strokes delivered to the hospital in the period of the therapeutic window are mild neurological symptoms, the age over 80 years and poly-morbidity of patients. Conclusion. It is necessary to adopt a series of measures aimed at advancing the efficiency of the EMS teams and rising awareness within the general public in order to reduce mortality of patients with ischemic strokes through increasing frequency of reperfusion therapy administration.

Idarucizumab in Dabigatran-Treated Patients with Acute Ischemic Stroke Receiving Alteplase: A Systematic Review of the Available Evidence.

Background and PurposeCurrent guidelines do not recommend the use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who receive direct oral anticoagulants. While the humanized monoclonal antibody idarucizumab can quickly reverse the anticoagulant effects of the thrombin inhibitor dabigatran, safety data for subsequent tissue plasminogen activator treatment are sparse. Here, we review current knowledge about dabigatran reversal prior to systemic reperfusion treatment in acute ischemic stroke.MethodsWe performed a systematic review of all published cases of intravenous tissue plasminogen activator treatment following the administration of a dabigatran antidote up to June 2017 and added five unpublished cases of our own. We analyzed clinical and radiological outcomes, symptomatic post-thrombolysis intracranial hemorrhage, and other serious systemic bleeding. Additional endpoints were allergic reaction to idarucizumab, and venous thrombosis in the post-acute phase.ResultsWe identified a total of 21 patients (71% male) with a median age of 76 years (interquartile range 70–84). The median National Institute of Health Stroke Scale score at baseline was 10 (n = 20, interquartile range 5–11) and 18/20 patients (90%) had mild or moderate stroke severity. The time from symptom onset to start of tissue plasminogen activator was 155 min (n = 18, interquartile range 122–214). The outcome was unfavorable in 3/19 patients (16%). There was one fatality as a result of a symptomatic post-thrombolysis intracranial hemorrhage, and two patients experienced an increase in the National Institute of Health Stroke Scale compared with baseline. One patient had a recurrent stroke. No systemic bleeding, venous thrombosis, or allergic reactions were reported.ConclusionExperience with idarucizumab administration prior to tissue plasminogen activator treatment in acute ischemic stroke is limited. Initial clinical experience in less severe stroke syndromes and short time windows seems favorable. Larger cohorts are required to confirm safety, including bleeding complications and the risk of thrombosis.