Thrombolytic Agents Research Articles

Sonothrombolysis for Ischemic Stroke.

Stroke is a major cause of death and disability globally, with ischemic stroke being the predominant mechanism. While spontaneous recanalization may occur, significant neuronal injury would have occurred in the interim. Intravenous thrombolysis administered within the first 4.5 h after stroke onset and endovascular thrombectomy within 24 h in patients with a salvageable penumbra improves functional independence. Ultrasound has been shown in both in vivo and in vitro models to enhance clot lysis, even more-so in the presence of thrombolytic agents. The use of transcranial Doppler and transcranial color-coded Doppler ultrasound in acute IS has been reported in case series, case-controlled studies, and clinical trials. While ultrasound at a frequency of 300 kHz increases the risk of intracranial hemorrhage, the 2 MHz range ultrasound aids thrombolysis and improves recanalization without significantly increasing the risk of symptomatic intracranial hemorrhage. Despite this, functional independence was not increased in clinical trials, nor was a benefit shown with the adjunctive use of microbubbles or microspheres. Nonetheless, newer technologies such as endovascular ultrasound, endovascular delivery of microbubbles, and thrombolytic-filled microbubbles await clinical trials. More evidence is needed before sonothrombolysis can be routinely used in the hyperacute management of ischemic stroke.

Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection

BackgroundThrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited.MethodsWe conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage.ResultsThe trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P=0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively.ConclusionsTenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.)

Abstract TP66: Decreased Order to Administration Times Following Transition to Tenecteplase for Acute Ischemic Stroke

Introduction: Alteplase was the first approved tissue plasminogen activator and standard of care for acute ischemic stroke (AIS). The utilization of Tenecteplase as a thrombolytic agent in AIS has offered many organizations several advantages over Alteplase, including ease of preparation and administration. Both thrombolytic agents require a Physician's order and reconstitution by a certified Pharmacist or Registered Nurse prior to administration. Our academic comprehensive stroke center transitioned from Alteplase to Tenecteplase as standard thrombolysis for acute ischemic stroke in November 2022. Treatment times were monitored to explore the benefits of a single bolus administration. Methods: A retrospective chart review was conducted at a single academic comprehensive stroke center. Patients were included if they received thrombolytic therapy in the Emergency Department for a diagnosis of AIS. Patients prior to November 2022 received Alteplase, and those after November 2022 received Tenecteplase. We evaluated the time frame for the medication bolus order for Alteplase and Tenecteplase to the administration time. Results: Of 140 patients screened, 108 were included in the study, with 51 in the alteplase group and 57 in the Tenecteplase group. Mean order to administration times were 10.9 minutes in the alteplase group and 7.37 minutes in the Tenecteplase group, with statistical significance (P=0.0052). There was no significant difference in mean door-to-needle time (59.27 Alteplase vs 53.09 Tenecteplase, P= 0.1803). Conclusions: In a single CSC, the transition from Alteplase to Tenecteplase reduced the order to administration time by 3.53 minutes. The decreased administration time highlights one of Tenecteplase’s potential advantages. Further review is necessary to evaluate additional stroke metrics and clinical outcomes.

Antidiabetic and Thrombolytic Activities of Some Selected Medicinal Plants in High Fat Diet and Dexamethasone-Induced Type 2 Diabetic Rats

Background: Type-2 diabetes (T2D) is a hypercoagulable and hypofibrinolytic condition that predisposes to cardiovascular and thrombotic complications. We screened three medicinal plants (Albizzia chevalieri, Newbouldia laevis and Leptadenia hastate) for their antidiabetic and thrombolytic activities.
 Methods: T2D was induced with high fat diet and dexamethasone. Following induction, rats were grouped into 6 (n=8 rats); control, untreated, treated (500mg/kg body weight (BW) metformin only) or treated (300mg/kg BW leaf extracts). The rats were treated for two weeks and euthanized. About 2ml of the collected blood was used for thrombolytic activity assay while the rest was processed, and the recovered serum utilised for biochemical and hormonal assays.
 Results: Rats treated with extracts had significantly (p<0.05) lowered concentrations of serum glucose, TG, LDL-cholesterol, VLDL- cholesterol and increased HDL-cholesterol compared to untreated rats. Extracts also lowered (p<0.05) the serum insulin concentration on day 14 compared to untreated rats. Albizzia chevalieri, Newbouldia laevis and Leptadenia hastata showed 48.90%, 39.20% and 37.69% clot lysis activities respectively which was significantly higher (p<0.001) than distilled water, while streptokinase produced a substantial clot lysis of 93.70%.
 Conclusions: The leaf extracts of Albizzia chevalieri, Newbouldia laevis and Leptadenia hastata have antidiabetic and thrombolytic activities in type-2 diabetic rats and thus, can be potentially used as combined antidiabetic and thrombolytic agents with in vivo effects in type-2 diabetic patients.

Improving the longitudinal spot width of an optimizingly designed point-like scatterer-arrayed transcranial ultrasonic lens

As a non-invasive therapy to promote the effect of the thrombolytic agent in the acute phase of cerebral infarction, transcranial irradiation by ultrasonic waves at the site of the occlusion has been validated and is expected to achieve clinical application. Such irradiation may, however, cause damage to the brain by interference of reflected waves within the skull. In order to avoid such a phenomenon, we proposed a transcranial acoustic lens formed by optimizing the arrangement of point-like scatterers. The optimum arrangement of scatterers was determined so that the sound field vanishes within the skull except at the focus(es) and becomes higher at the focus(es) than in the surrounding regions. The ultrasonic waves are strongly scattered by air bubbles in the water-like medium, so we attempted to install a crossbar switch in the medium covering the head and constructed an acoustic lens by producing an instantaneously adaptive air bubble array. This lens can focus an incident plane wave to the diffraction limit in the direction perpendicular to the incident direction, while the peak width in the propagation direction is more than five times higher. In this work, in order to practically improve it, we propose to arrange a point-like scatterer so as to partially cover the head and further increase the number of layers. The shape of the skull is modeled based on CT data, and more realistic parameters are employed than in a previous paper [T. Ueta, J. Appl. Phys. 132, 144504 (2022)].

Abstract TMP110: A Novel Model of Ischemia in Rats With Middle Cerebral Artery Occlusion Using a Radiopaque Blood Clot and a Microcatheter Under Fluoroscopy

Introduction: Conventional thromboembolic stroke model requires ligation of the ECA, which is problematic for research of thrombolytic agents because cerebral blood flow is different from human stroke. We aimed to develop a novel thromboembolic stroke model that does not require arterial ligation, using a radiopaque blood clot and microcatheter. Methods: Using male Sprague Dawley rats (n=14) and two sham operated rats were included, a microcatheter (inner diameter, 0.42mm; outer diameter, 0.55mm) was navigated from the caudal ventral artery to the left ICA using fluoroscopy. A blood clot (0.86 mm in diameter, 3 mm in length) containing zirconium dioxide was advanced in the catheter by injection of physiological saline to establish local occlusion. Both fluoroscopy at 1, 3, 6, 24 h and TTC staining at 24 h after stroke model creation were performed. Neurological deficit score was measured. Results: The success rate in selectively embolized of ACA and MCA bifurcation was 93% (13 of 14 cases). The median operating time was 7 min (interquartile range; 4-15 min). The median infarct volume (mm 3 ) was 248 (interquartile range; 239-280) 24 h after occlusion. Neurological deficit scores before and at 1, 3, 6, and 24 h after model creation differed significantly ( P < 0.001). Fluoroscopy showed the position of the radiopaque blood clot remains the same for 24 h after creating the model in 12 of 13 cases (92%). Sham-operated rats revealed no infarction and no neurological deficit. Conclusions: We present a novel rat model for focal infarct only in the MCA territory using a radiopaque blood clot. Fluoroscopy was able to identify whether the blood clot could migrate and recanalize.

Pediatric Central Venous Access Device Lock Solutions: A Network Meta-analysis.

Central venous access device (CVAD) locks are routine interventions used to prevent and treat complications, such as infection, thrombosis, and catheter occlusion. To compare and rank lock-solutions for prevention or treatment of complications in pediatrics. Design Systematic review and network meta-analysis. Five databases and 2 clinical trial registries were searched. Published and unpublished randomized controlled trials that enrolled pediatric patients with a CVAD and compared the effectiveness of lock-solutions. Data extraction was conducted by 2 reviewers. Odds ratio (OR) for prevention or treatment of CVAD-associated bloodstream infection (BSI), thrombosis, occlusion, CVAD-failure, and mortality were calculated, with point estimates ranking lock-solutions. Twenty-nine studies were included. Chelating agents and antibiotic locks given as prevention were associated with lower odds (OR: 0.11; 95% confidence interval [CI]: 0.02-0.67; moderate-quality; OR: 0.19; 95% CI: 0.05-0.79, high-quality, respectively) of CVAD-associated BSI compared with heparinized saline (reference). Preventative thrombolytic agents had lower odds (OR: 0.64, 95% CI: 0.44-0.93; low-quality) of CVAD occlusion, whereas ethanol had higher odds (OR: 2.84, 95% CI: 1.31-6.16; high-quality) compared with heparinized saline (reference). No lock solution had effects on thrombosis prevention or treatment, CVAD-failure, CVAD-associated BSI treatment failure, or mortality. There was substantial uncertainty around the point estimates because of the limited number of studies for outcomes and study heterogeneity. More high-quality studies are needed to confirm the efficacy of lock solutions. Chelating agents and antibiotic locks may be effective for CVAD-associated BSI prevention in pediatrics. Thrombolytic agents can be an option for CVAD occlusion prevention, whereas ethanol may not be recommended.

Reteplase versus alteplase for acute ischaemic stroke within 4.5 hours (RAISE): rationale and design of a multicentre, prospective, randomised, open-label, blinded-endpoint, controlled phase 3 non-inferiority trial

Background and purposeReteplase is the third generation of alternative thrombolytic agent. We hypothesis that reteplase will be non-inferior to alteplase in achieving excellent functional outcome at 90 days among eligible...

Ultrasound-powered hydrogen peroxide-responsive Janus micromotors for targeted thrombolysis and recurrence inhibition

Thrombosis seriously endangers human health with high incidence and mortality worldwide, and the clinical treatment is challenged by low bioavailability of thrombolytic agents, high bleeding risk and thrombosis relapse. Herein, ultrasound-powered Janus micromotors with stimuli-responsive multiple release capabilities are developed for efficient thrombolysis and inhibition of thrombosis recurrence. Resveratrol-loaded hyaluronic acid (HARes) nanoparticles (NPs) and urokinase plasminogen activator (uPA) were entrapped into H2O2-sensitive poly(1,4-cyclohexanedimethanol-co-oxalate) (POX) microparticles (MPs), followed by polydopamine capping and RGD grafting to obtain Janus rJPox@u-HARes MPs. After RGD-mediated delivery to the thrombus site, the peroxalate ester bonds of POX are oxidized by the elevated H2O2 to produce CO2, and the MP collapse accelerates the local release of uPA and HARes NPs. The resulting CO2 bubbles amplify the cavitation effect of ultrasound to promote thrombus penetration and site-specific uPA thrombolysis. The endothelial cell targeting and sustained resveratrol release from HARes NPs dramatically improve endothelial cell viability, nitric oxide production and migration. Compared with free drug administration, the uPA loading into MPs significantly extends the half-life (15 folds) and bioavailability (7 folds), while the resveratrol inoculation into NPs increases the bioavailability 29 times. On an acute lower limb thrombosis model, the thrombus accumulation of MPs is promoted by RGD-mediated interactions with the activated platelets and ultrasound-driven penetration into thrombi, leading to almost full removal of blood clots. The H2O2-scavenging capability of POX, sustained resveratrol release and efficient thrombolysis alleviate oxidative stresses, eliminate coagulation biomarkers and repair the damaged endothelial layer to effectively inhibit thrombosis relapse. It is demonstrated that rJPox@u-HARes/US treatment could not only achieve safe and site-specific thrombolytic therapy at the early stage but also restore vascular homeostasis to effectively prevent thrombosis recurrence.

In vitro assessment of thrombolytic potential of red and white ginger (Zingiber officinale)

Background: Cardiovascular diseases (CVDs) are a leading cause of death, and their pathogenesis is commonly attributed to thrombosis. Although existing medications are effective and fast-acting for thrombosis management, they tend to be expensive and cause severe side effects. Plant-based thrombolytic agents are actively sought after as inexpensive and safe alternatives for the treatment and prevention of thrombosis. Red ginger (Zingiber officinale var. rubrum) and white ginger (Zingiber officinale var. officinale) are widely used in foods and beverages and are believed to confer a wide variety of health benefits. Objective: This study aims to elucidate the thrombolytic and fibrinolytic potential of red and white ginger extracts in vitro.Methods: In this study, in vitro analyses were performed using erythrocyte liberation, euglobulin degradation, fibrin degradation, and fibrin zymography assays. The ability of crude enzyme extracts from both red (rgEx) and white ginger (wgEx) to degrade blood clots was analyzed using the erythrocytes liberation assay. Then, the thrombolytic and fibrinolytic activities of rgEx and wgEx were evaluated using euglobulin and fibrin degradation assays, both of which were visualized using Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE). Finally, fibrinolytic enzymes were identified using a fibrin zymography assay. Results: Red and white ginger extracts were found to have strong thrombolytic properties via high total liberated erythrocyte count from the erythrocyte liberation assay. The ginger extract proteases can rapidly degrade euglobulin and fibrin, with their priority order beginning with A

Safety and efficacy of N-acetylcysteine (NAC) as an adjunct to standard treatment in patients with acute ischemic stroke: a randomized controlled pilot trial (NACTLYS)

There is a pressing clinical need for thrombolytic agents that can effectively disaggregate arterial thrombi in acute ischemic stroke without significantly increasing the risk of bleeding. This pilot study aimed to investigate the safety and efficacy of N-acetylcysteine (NAC) as an adjunctive therapy to intravenous recombinant tissue plasminogen activator (rtPA or alteplase). A randomized, open-label, blinded assessor pilot study was conducted. Patients presenting with an acute ischemic stroke within 4.5 h from onset were randomized into two groups: intravenous NAC and rtPA or rtPA alone. Primary outcomes included intracerebral hemorrhage, symptomatic intracerebral hemorrhage, extracranial bleeding, and adverse reactions. Secondary outcomes comprised major neurological improvement assessed by (National Institute of Health Stroke Scale) NIHSS at 24 h, recanalization on first run of angiography in patients who underwent thrombectomy or on repeat vascular imaging at 24 h, modified Rankin scale, and three-month mortality. Forty patients were enrolled, with 21 receiving only rtPA and 19 receiving NAC with rtPA. Baseline characteristics were comparable among groups. No significant differences were observed in adverse events (p = 0.99), intracranial hemorrhage (p = 0.21), symptomatic intracerebral hemorrhage (p = 0.47), or extracranial bleeding (p = 0.21). Median NIHSS at 24 h was significantly lower in the intervention group (p = 0.03). Functional outcomes and three-month mortality were similar between groups (p = 0.85 and p = 0.99 respectively). The co-administration of N-acetylcysteine with alteplase did not significantly alter safety profiles, morbidity, or mortality at 3 months. While no substantial differences were noted, a slightly improved early neurological outcome was observed in the intervention arm. The study's findings were constrained by a small sample size, emphasizing the necessity for future large-scale trials to comprehensively evaluate the safety and efficacy of N-acetylcysteine as a thrombolytic agent in acute ischemic stroke.Trial Registration Clinical Trials Registry India—CTRI/2019/05/019305.

Improving stroke outcomes in hyperglycemic mice by modulating tPA/NMDAR signaling to reduce inflammation and hemorrhages

AbstractThe pharmacological intervention for ischemic stroke hinges on intravenous administration of the recombinant tissue-type plasminogen activator (rtPA, Alteplase/Actilyse) either as a standalone treatment or in conjunction with thrombectomy. However, despite its clinical significance, broader use of rtPA is constrained because of the risk of hemorrhagic transformations (HTs). Furthermore, the presence of diabetes or chronic hyperglycemia is associated with an elevated risk of HT subsequent to thrombolysis. This detrimental impact of tPA on the neurovascular unit in patients with hyperglycemia has been ascribed to its capacity to induce endothelial N-methyl-D-aspartate receptor (NMDAR) signaling, contributing to compromised blood-brain barrier integrity and neuroinflammatory processes. In a mouse model of thromboembolic stroke with chronic hyperglycemia, we assessed the effectiveness of rtPA and N-acetylcysteine (NAC) as thrombolytic agents. We also tested the effect of blocking tPA/NMDAR signaling using a monoclonal antibody, Glunomab. Magnetic resonance imaging, speckle contrast imaging, flow cytometry, and behavioral tasks were used to evaluate stroke outcomes. In hyperglycemic animals, treatment with rtPA resulted in lower recanalization rates and increased HTs. Conversely, NAC treatment reduced lesion sizes while mitigating HTs. After a single administration, either in standalone or combined with rtPA-induced thrombolysis, Glunomab reduced brain lesion volumes, HTs, and neuroinflammation after stroke, translating into improved neurological outcomes. Additionally, we demonstrated the therapeutic efficacy of Glunomab in combination with NAC or as a standalone strategy in chronic hyperglycemic animals. Counteracting tPA-dependent endothelial NMDAR signaling limits ischemic damages induced by both endogenous and exogenous tPA, including HTs and inflammatory processes after ischemic stroke in hyperglycemic animals.

Comparison of Tetrasodium EDTA 4% with Sodium Citrate 4% as Line-Locking Solutions at 2 Tertiary Hemodialysis Centres.

The patency of central venous catheters (CVCs) in patients undergoing hemodialysis (HD) is maintained by instilling sodium citrate 4% (SC 4%) locking solution. Alteplase, a thrombolytic agent, is administered to restore function if patency is lost. To compare SC 4% with a new line-locking solution, ethylenediaminetetraacetic acid 4% (EDTA 4%), in terms of CVC patency and alteplase use. This retrospective chart review included all HD patients who were switched from SC 4% to EDTA 4% locking solution at 2 tertiary HD centres between June and December 2021. Patients were switched to EDTA 4% if they had high usage of alteplase (receiving ≥ 2 doses of alteplase in a 2-week period). For each line-locking agent, HD pump speeds and alteplase use were analyzed over 2 consecutive 12-week periods. Mean serum calcium and ionized calcium values were recorded during each period. A cost analysis was also performed. A total of 37 HD patients were switched to EDTA 4% during the study period. There was no difference in mean HD pump speed between SC 4% and EDTA 4% (307.7 vs 305.1 mL/min, p = 0.48). The number of catheter-use-days on which alteplase was required declined significantly, from 313 days with SC 4% to 94 days with EDTA 4% (p < 0.001), with an overall cost reduction of 34% ($13 183.21). The decrease in alteplase usage was primarily driven by 1 of the 2 sites. A statistically significant decrease in mean ionized calcium at site 2 (from 1.12 to 1.1 mmol/L, p = 0.037) was noted. As well, an intraluminal interaction between EDTA 4% and serum calcium caused 6 cases of low serum calcium. This study showed that use of EDTA 4% as a line-locking agent reduced alteplase usage in the CVCs of HD patients while maintaining adequate pump speed (i.e., ≥ 300 mL/min).

Molecular Docking of Interaction between D7 Protein from the Salivary Gland of Aedes aegypti and Leukotriene A4 for Developing Thrombolytic Agent

The salivary glands of mosquitoes contain protein molecules that facilitate blood-feeding. One important protein in Aedes aegypti (Ae. aegypti) salivary glands is the D7 protein, which is known to inhibit platelet aggregation by binding to leukotriene A4 molecules upon blood-feeding. Leukotriene A4 is known as a molecule that improves platelet aggregation. This ability to bind to leukotriene A4 demonstrates the potential of a new thrombolytic agent. This can be investigated through an in-silico study using the molecular docking method. The present study involved the 3D structure of the D7 protein and the Leukotriene A4 ligand. It also comprised preparing their structures, validating the molecular docking method, and analyzing the outcomes. The result of the molecular docking documented an ΔG value of 6.63 kcal/mol, which signified stable and spontaneous binding between the D7 protein and the leukotriene A4. The active site of the D7 protein when binding to the leukotriene A4 ligand involves several amino acid residues, namely GLN 177, TYR 178, ARG 176, VAL 193, ILE 175, MET 194, PHE 154, PHE 186, HIS 189, TYR 248 and PHE 264. The ability to bind to leukotriene A4, as an inducer of platelet aggregation, evidences the potential as a novel thrombolytic agent.

Application of microbial enzymes in medicine and industry: current status and future perspectives.

Microbes are a major source of enzymes due to their ability to be mass-cultivated and genetically modified. Compared with plant and animal enzymes, microbial enzymes are more stable and active. Enzymes are generally classified into six classes based on their reaction, substrate specificity and mechanism of action. In addition to their application in medicine for treating diseases, these compounds are used as anti-inflammatory, thrombolytic and digestive agents. However, challenges such as immunogenicity, tissue specificity and short in vivo half-life make clinical trials complex. Enzymes are metabolic catalysts in industry and their production and extraction must be optimized to preserve profitability due to rising demand. The present review highlights the increasing importance of bacterial enzymes in industry and medicine and explores methods for their production, extraction and purification.

Penicillium citrinum CFAM 521 Isolated From the Amazon Region: A Novel Source of a Fibrinolytic Enzyme.

Fibrinolytic agents are essential in treating thrombosis, playing a critical role in improving survival rates in cardiovascular diseases. Microbial fibrinolytic proteases have emerged as promising alternatives due to their affordability, specificity, lower toxicity, and reduced side effects. Consequently, the search for microorganisms capable of producing these enzymes has gained significant economic importance in the pharmaceutical industry. This study reports and characterizes a novel fibrinolytic enzyme produced by Penicillium citrinum CFAM 521, a strain isolated from the Amazon region. The enzyme was purified using a polyethylene glycol (PEG)-phosphate salt aqueous two-phase system (ATPS). The effects of PEG molecular weight, PEG concentration, and phosphate concentration on the protease partition coefficient (K) were evaluated through a 22 full factorial design. The enzyme exhibited both fibrinolytic and fibrinogenolytic activities. After partitioning in a two-phase system with 10% (w/w) PEG and 15% (w/w) sodium phosphate, the fibrinolytic proteases were predominantly retained in the salt-rich bottom phase (K = 0.33). The enzyme has a molecular weight of 34 kDa, with optimal pH and temperature at 9°C and 37°C, respectively. Inhibitory analysis confirmed that it is a serine protease, and its activity was enhanced by the addition of Mn2+. Notably, the enzyme exhibited no hemolytic activity. Therefore, P. citrinum CFAM 521 represents a novel source of fibrinolytic enzymes, highlighting its potential as an alternative for the development of thrombolytic agents.

Multimodal Approach for the Treatment of Extensive Bilateral Iliofemoral Deep Vein Thrombosis

Abstract Iliofemoral vein thrombosis is the primary cause of deep vein thrombosis (DVTs) in the lower extremities in around 25% of the cases. Restoration of venous outflow is the primary goal in the management of DVT which can be achieved by combined endovascular techniques such as balloon venoplasty and/or stenting, thrombectomy, and pharmacomechanical thrombolysis. At presently, percutaneous mechanical thrombectomy (PMT) devices, such as rheolytic thrombectomy device, are replacing conventional approaches for clot removal. Although the use of rheolytic thrombectomy device for DVT is associated with the risk of intravascular hemolysis, we report a safe and successful use of multimodal approach using rheolytic thrombolytic device for the management of a case of bilateral iliofemoral DVT. In our study, we noticed early relief in pain and reduced lower limb edema in a week with a reduced dose of thrombolytic agent and hospital stay in a 44-year-old male who was admitted with bilateral extensive iliofemoral DVT using a multimodal approach.

Analysis of Thrombolytic Agents in Intraventricular Hemorrhage: A Systematic Review and Meta-Analysis.

To determine the effectiveness of extraventricular drainage (EVD) combined with fibrinolytics in reducing morbidity and mortality rates associated with intraventricular cerebral hemorrhage (IVH). A literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO registration number: CRD42022332152). Articles were selected from various sources, including PubMed, Trip Database, LILACS, Cochrane Library, and ScienceDirect. Clinical trials focusing on IVH treatment using EVD and/or fibrinolytics were considered. The Risk of Bias in Non-randomized Studies of Interventions (ROB 2) tool was employed for bias assessment. A fixed-effects regression model was used following heterogeneity analysis. Treatment effectiveness was evaluated based on mortality outcomes. A total of 531 patients from four studies were included. The use of fibrinolytics significantly decreased IVH mortality compared with a placebo. The odds ratio (OR) for recombinant tissue plasminogen activator (rtPA) or alteplase was 0.54 [0.36; 0.82]. For urokinase (UK), the OR was 0.21 [0.03; 1.54], rendering it statistically non-significant. The overall OR was 0.52 [0.35; 0.78], and the heterogeneity I2 was 0% (indicating low heterogeneity). While EVD alone is a common approach for managing hydrocephalus, its effectiveness is limited by potential blockages and infections. Combining EVD with UK or rtPA demonstrated improved patient outcomes. rtPA stands out as a reliable and effective option, while limited data are available regarding UK's effectiveness in reducing IVH mortality.

Acute Pulmonary Embolism Following Hemorrhagic Stroke

Background: Venous thromboembolism results from extended immobilization following intracerebral hemorrhage. Massive pulmonary embolism in association with right heart failure is a life-threatening condition and requires treatment with anticoagulants or thrombolytic agents. There are no guidelines for treatment of pulmonary embolism with recent hemorrhagic stroke and these medicines are contraindicated, as they may induce farther hemorrhage.

“Hemorrhagic Transformation Following Thrombolytic Therapy in Acute Ischemic Stroke: A Case Series of 5 Patients”

Stroke stands as a global health menace, causing substantial disability and mortality. Timely intervention, specifically within the critical "Golden Hour" following acute ischemic stroke, is imperative. Thrombolytic agents like tissue plasminogen activators (tPA) are pivotal for clot dissolution and blood flow restoration, yet their use introduces the risk of hemorrhagic transformation (HTF).In a recent case series involving five patients receiving thrombolytic therapy for acute ischemic stroke, we illuminate the occurrence of post-treatment HTF, its clinical ramifications, and the intricate challenges in its management. Early intervention in acute ischemic stroke aims to safeguard at-risk brain tissue, with thrombolytic therapy, notably tPA, serving as a primary treatment avenue. However, the associated risk of HTF hovers around 30%–35%, influenced by factors like age, comorbidities, and infarct size. The vulnerable ischemic penumbra, marked by a compromised blood-brain barrier and free radical generation, is particularly susceptible. Treatment decisions, guided by the National Institutes of Health Stroke Scale (NIHSS), pivot on stroke severity assessment, emphasizing the need for vigilant post-treatment monitoring. In conclusion, navigating the delicate balance between the benefits of early thrombolysis and the risks of HTF remains a persistent challenge in optimizing outcomes for acute ischemic stroke patients.