Safety Of Thrombolysis Research Articles

Stroke Thrombolysis in the Elderly: A Moroccan Retrospective Study

Background: Age increases the risk of mortality and poor prognosis following a stroke. The benefits of intravenous thrombolysis (IVT) in elderly patients have been well established. However, the outcomes in daily clinical practice may differ from those reported in other studies. The objectives of our study are to evaluate the effectiveness and safety of thrombolysis in elderly stroke patients and provide local data that can inform clinical practices in similar settings and raise awareness about specific challenges in treating elderly patients with ischemic stroke. Methods: We conducted a retrospective, cross-sectional, descriptive, and analytical study in the neurology department of Hassan II University Hospital in Fez, Morocco, from May 2015 to March 2021. All elderly patients aged ≥ 80 years within 6 h of onset who received intravenous thrombolysis were recruited. The primary outcomes were the rate of hemorrhagic transformation, NIHSS score at 24 h after IV thrombolysis and the rate of death within the first 7 days. Secondary outcomes were functional status at 3 months, assessed using the modified Rankin Scale (mRS). Our results were interpreted in light of the main studies in the literature. Results: 41 patients (58.5 % female, aged 84 ± 3.5 y.o) all received IV thrombolysis (tenecteplase 85.4% vs alteplase 14.6%) were included. The mean NIHSS score before IV thrombolysis was 13 (range, 3-20) and that 24 h after IV thrombolysis was 10 (rang, 1-19). Hemorrhagic transformations occurred in 31.7% of the patients within 7 days after onset (9.8% HI1, 9.8% HI2, 2.4% PH1, 9.8% PH2), and all of these cases were asymptomatic. The rate of death within the first 7 days was 22%. Among living patients, the median three months mRS was 3. The mortality rate at three months was 26.8% (n=11). However, there was no significant association between these outcomes and the occurrence of ICH after IVT. Conclusion: Despite the higher mortality rate in our sample, IV thrombolysis ...

Thrombolysis exacerbates cerebrovascular injury after ischemic stroke via a VEGF-B dependent effect on adipose lipolysis.

Cerebrovascular injuries leading to edema and hemorrhage after ischemic stroke are common. The mechanisms underlying these events and how they are connected to known risk factors for poor outcome, like obesity and diabetes, is relatively unknown. Herein we demonstrate that increased adipose tissue lipolysis is a dominating risk factor for the development of a compromised cerebrovasculature in ischemic stroke. Reducing adipose lipolysis by VEGF-B antagonism improved vascular integrity by reducing ectopic cerebrovascular lipid deposition. Thrombolytic therapy in ischemic stroke using tissue plasminogen activator (tPA) leads to increased risk of hemorrhagic complications, substantially limiting the use of thrombolytic therapy. We provide evidence that thrombolysis with tPA promotes adipose tissue lipolysis, leading to a rise in plasma fatty acids and lipid accumulation in the ischemic cerebrovasculature after stroke. VEGF-B blockade improved the efficacy and safety of thrombolysis suggesting the potential use of anti-VEGF-B therapy to extend the therapeutic window for stroke management.

Efficacy and Safety of Thrombolysis in COVID-19 Related ARDS.

COVID-19 causes significant pulmonary microthrombi in some individuals, leading to ARDS and death. Thrombolysis could be an effective approach in some patients with severe ARDS. We describe our experience with the usage of thrombolytic agents in critically ill COVID-19 patients who were in worsening respiratory failure. Retrospective chart analysis was done in patients who were thrombolysed between May 2020-Sept 2020. Analysis was done to find out factors associated with improvement in oxygenation and survival. Twenty-seven patients with severe ARDS [all had respiratory rate >30, FiO2 >0.6 (on NIV/HFNC) and PiO2/FiO2 ratio <120] were thrombolysed in our ICU for COVID19 causes. C.T. Pulmonary Angiography could not be done in any of the 27 patients due to poor general condition, but 2D echo was normal in most (5 had dilated RA, RV), and none of the patients was in shock. So, there was no conventional indication of thrombolysis in these patients, yet after thrombolysis, we observed dramatic changes in oxygenation (defined by a decrease in FiO2 by ≥0.2) in twenty patients. Five patients had a major bleed. Eleven patients survived (survival rate of 40.7%) and the survival rate was high {66% (8/12)} in patients who were thrombolysed within 2 days of oxygen requirement. In this unprecedented pandemic with high mortality rates, efficacy of early thrombolysis needs to be further explored in randomised controlled trials.

Safety of intravenous thrombolysis for ischemic stroke in patients with hematologic malignancies: A single institution experience

BackgroundData on safety of thrombolysis for acute ischemic stroke (AIS) in patients with hematologic malignancy is not well established. We report our single institution experience with thrombolysis in this patient population. MethodsWe identified patients with pathology-confirmed hematologic malignancy from 2000-2022. Primary exposure was presence of AIS and receipt of intravenous (IV) thrombolysis. Primary outcome was safety of IV thrombolysis in this patient population. Safety was measured through imaging review for hemorrhagic transformation, post-stroke mortality, and modified Rankin Scale (mRS) at 90 days. ResultsAmong 45,894 patients with hematologic malignancy, 1,099 (2.4%) were identified as having a suspected AIS. Twenty (1.8%) received IV tissue plasminogen activator (tPA) for AIS, three underwent endovascular intervention, and 17 had AIS confirmed on MRI. Two patients with confirmed AIS experienced hemorrhagic transformation, one of which was symptomatic. Most patients (n=10, 59%) were functionally independent (mRS 0-2) at 90 days post-stroke, including all patients with active hematologic malignancy at the time of stroke (n=3). Four patients died within 90 days of AIS. None of these deaths were patients with active hematologic malignancy at the time of stroke. ConclusionsWithout other contraindications, IV alteplase should be considered for management of AIS in patients with hematologic malignancy. The safety profile of tPA administration in this patient population may be similar to the general population, whether underlying hematologic malignancy is active or in remission.

Building Evidence on Safety of Thrombolysis for Patients Undergoing Direct Oral Anticoagulant Treatment

Building Evidence on Safety of Thrombolysis for Patients Undergoing Direct Oral Anticoagulant Treatment

DWI-FLAIR mismatch guided thrombolysis in patients without large-vessel occlusion: real-world data from a comprehensive stroke centre

IntroductionA significant proportion of ischaemic stroke patients present with unknown symptom onset time. DWI-FLAIR mismatch on MRI can help to identify those eligible for thrombolysis. We set out to analyse the short-term efficacy and safety of thrombolysis in a real-world setting. MethodsA retrospective single-centre observational study was conducted. We collected data between January 2017 and April 2020. Patients with a large vessel occlusion (LVO) were excluded. Outcomes were compared between thrombolysed patients and those who did not receive alteplase due to lack of DWI-FLAIR mismatch or other contraindications. We analysed baseline and discharge NIHSS scores for efficacy and defined good outcome as any neurological improvement (ANI) on the NIHSS. In terms of safety, the presence and severity of intracerebral haemorrhage on follow-up imaging was analysed, and mortality at 90 days assessed. ResultsSeventy-one patients were included in this study, of whom 29 received thrombolysis. Significantly more patients had ANI in the thrombolysed group (OR, 3.16; 95% CI, 1.178–8.479; p = 0.020). In a multivariable logistic regression analysis, only thrombolysis correlated with ANI (OR, 3.051; 95% CI, 1.135–8.206; p = 0.027). Two thrombolysed patients suffered intracerebral haemorrhage (6.90%), of whom one was symptomatic and eventually fatal. We did not find a significant difference in 90-day mortality between the two groups (OR, 0.81, 95% CI, 0.134–4.856; p = 1.000). ConclusionsOur real-world data demonstrate that thrombolysis based on DWI-FLAIR mismatch in patients without LVO has an early beneficial effect. The rate of intracerebral haemorrhage was similar to this complication reported in large thrombolysis trials with known onset times.

Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis.

Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran, potentially allowing for thrombolysis. This nation-wide observational cohort study, systematic review, and meta-analysis evaluated the efficacy and safety of thrombolysis preceded by dabigatran-reversal in people with acute ischemic stroke. We recruited people undergoing thrombolysis following dabigatran-reversal at 17 stroke centers in Italy (reversal-group), people on dabigatran treated with thrombolysis without reversal (no-reversal group), and age, sex, hypertension, stroke severity, and reperfusion treatment-matched controls in 1:7 ratio (control-group). We compared groups for symptomatic intracranial hemorrhage (sICH, main outcome), any brain hemorrhage, good functional outcome (mRS 0-2 at 3 months), and death. The systematic review followed a predefined protocol (CRD42017060274), and odds ratio (OR) meta-analysis was implemented to compare groups. Thirty-nine patients in dabigatran-reversal group and 300 matched controls were included. Reversal was associated with a non-significant increase in sICH (10.3% vs 6%, aOR = 1.32, 95% CI = 0.39-4.52), death (17.9% vs 10%, aOR = 0.77, 95% CI = 0.12-4.93) and good functional outcome (64.1% vs 52.8%, aOR = 1.41, 95% CI = 0.63-3.19). No hemorrhagic events or deaths were registered in no-reversal group (n = 12). Pooling data from 3 studies after systematic review (n = 1879), reversal carried a non-significant trend for sICH (OR = 1.53, 95% CI = 0.67-3.50), death (OR = 1.53, 95% CI = 0.73-3.24) and good functional outcome (OR = 2.46, 95% CI = 0.85-7.16). People treated with reperfusion strategies after dabigatran reversal with idarucizumab seem to have a marginal increase in the risk of sICH but comparable functional recovery to matched patients with stroke. Further studies are needed to define treatment cost-effectiveness and potential thresholds in plasma dabigatran concentration for reversal.

Efficacy and safety of thrombolytic therapy for portal venous system thrombosis: A systematic review and meta-analysis.

The role of thrombolytic therapy in patients with portal venous system thrombosis (PVST) remains ambiguous. This study aimed to systematically collect available evidence and evaluate the efficacy and safety of thrombolysis for PVST. Eligible studies were searched via PubMed, EMBASE, and Cochrane Library databases. Among the cohort studies, meta-analyses were performed to assess the outcomes of PVST patients receiving thrombolysis. Pooled proportions were calculated. Among the case reports and case series, logistic regression analyses were performed to identify the risk factors for outcomes of PVST patients receiving thrombolysis. Odds ratios (ORs) were calculated. Among the 2134 papers initially identified, 29 cohort studies and 131 case reports or case series were included. Based on the cohort studies, the pooled rates of overall response to thrombolytic therapy, complete recanalization of PVST, bleeding events during thrombolysis, further bowel resection, thrombosis recurrence, and 30-day mortality were 93%, 58%, 18%, 3%, 1%, and 4%, respectively. Based on the case reports and case series, acute pancreatitis (OR = 0.084), history of liver transplantation (OR = 13.346), and interval between onset of symptoms and initiation of thrombolysis ≤14 days (OR = 3.105) were significantly associated with complete recanalization of PVST; acute pancreatitis (OR = 6.556) was significantly associated with further bowel resection; but no factors associated with the overall response to thrombolytic therapy, bleeding events during thrombolysis, thrombosis recurrence, and 30-day mortality were identified or could be calculated. Early initiation of thrombolysis should be effective for the treatment of PVST. But its benefits for PVST secondary to acute pancreatitis are weakened.

CT- versus MRI-Based Imaging for Thrombolysis and Mechanical Thrombectomy in Ischemic Stroke: Analysis from the Austrian Stroke Registry.

Background and Purpose It is unclear whether a particular stroke imaging modality offers an advantage for the acute stroke treatment. The aim of this study was to compare procedure times, efficacy and safety of thrombolysis and/or thrombectomy based on computed tomography (CT) versus magnetic resonance imaging (MRI) acute stroke imaging. Methods Data of stroke patients who received intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) were extracted from a nationwide, prospective stroke unit registry and categorized according to initial imaging modality. Study endpoints included procedure times, symptomatic intracerebral hemorrhage (sICH), early neurological improvement, 3-month functional outcome by modified Rankin Scale (mRS) and mortality. Results Stroke patients (n=16,799) treated with IVT and 2,248 treated with MT were included. MRI-guided patients (n=2,599) were younger, had less comorbidities and higher rates of strokes with unknown onset as compared to CT-guided patients. In patients treated with IVT, no differences were observed regarding the rates of functional outcome by mRS 0–1 (adjusted odds ratio [OR], 0.87; 95% confidence interval [CI], 0.71 to 1.05), sICH (adjusted OR, 0.82; 95% CI, 0.61 to 1.08), and mortality (adjusted OR, 0.88; 95% CI, 0.63 to 1.22). Patients undergoing MT selected by MRI as compared to CT showed equal rates of functional outcome by mRS 0–2 (adjusted OR, 0.87; 95% CI, 0.65 to 1.16), sICH (adjusted OR, 0.9; 95% CI, 0.51 to 1.69), and mortality (adjusted OR, 0.62; 95% CI, 0.35 to 1.09). MRI-guided patients showed a significant intrahospital delay of about 20 minutes in both the IVT and the MT group. Conclusions This large non-randomized comparison study indicates that CT- and MRI-guided patient selection for IVT/MT may perform equally well in terms of functional outcome and safety.

Safety and outcomes of thrombolytic therapy in patients with pulmonary embolism and thrombocytopenia: A systematic review.

Thrombolysis is an established therapeutic modality for patients with high-risk (and some selected intermediate-risk) pulmonary embolism (PE) with hemodynamic instability. Physicians sometimes experience cases where both a high-risk PE and thrombocytopenia coexist. Although thrombocytopenia of < 100 × 103/mm3 is considered a contraindication in patients with ischemic stroke, the safety and outcomes of thrombolysis in patients with acute PE and thrombocytopenia are unknown. This systemic review aimed to pool data on the safety and outcomes of thrombolysis use in patients with PE and platelet count less than 150 × 103/mm3. Patients’ demographics, clinical characteristics, management, type of thrombolytic therapy, and outcomes were extracted and analyzed. Of 283 articles identified through the systematic search, 11 case reports fulfilled the inclusion criteria. The mean age of the patients was 52.27 years, and 54.5% were women. The median platelet level before thrombolysis was 65.50 × 103/mm3. Before thrombolysis was initiated, the lowest and highest platelet levels were 29 × 103/mm3 and 105 × 103/mm3, respectively. Alteplase was used in 10 patients and urokinase in one patient. One patient who had a massive PE died of aspiration pneumonia. Interestingly, no thrombocytopenia-related complications were reported. This systematic review highlights the potential benefits and safety of thrombolysis in patients with acute PE in the context of thrombocytopenia. Nevertheless, data available in the literature concerning this topic are scarce and limited to case reports. More extensive studies on the use of thrombolysis in patients with PE and thrombocytopenia are desperately needed.Systematic review registration: The protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42021286415.

An evaluation of the efficacy and safety of thrombolysis in patients with wake-up stroke using the combination of inflammatory factors Interleukin-6 and C-reactive protein with multi-mode magnetic resonance imaging

ObjectiveTo explore the efficacy and safety of using thrombolysis in patients with wake-up stroke (WUS). MethodsThe serum IL-6 and hs-CRP levels of the patients in both the experimental group and the standard group were measured before thrombolysis and at 1 and 24 h afterwards. National Institute of Health Stroke Scale (NIHHS) scores were also recorded at the same time points as well as at 10 and 90 d after thrombolysis, and modified Rankin Scale (mRS) scores were calculated before thrombolysis and at 10 and 90 d afterwards. The differences in all these observations before and after thrombolysis were then investigated. Results(1) The levels of serum IL-6 and hs-CRP in the experimental group and the standard group were higher than those in the healthy control group before thrombolysis (P < 0.05), indicating that higher levels of hs-CRP and IL-6 are risk factors for WUS (P < 0.05). (2) There were no significant differences in the serum hs-CRP and IL-6 levels of the patients in the experimental and standard groups before thrombolysis (P > 0.05). (3) The serum IL-6 and hs-CRP levels were positively correlated with the NIHHS scores in both the experimental group and the standard group (P < 0.05), and they correlated with the mRS scores at 90 d. ConclusionsInterleukin-6 and hs-CRP can be used as biological indicators of inflammatory injury and diagnosis of stroke, and the combined detection of IL-6 and hs-CRP is of importance in predicting a deterioration in stroke patients.

Tenecteplase and Alteplase for Thrombolysis of Acute Ischemic Stroke within 4.5 Hours: An Efficacy and Safety Study.

To compare the efficacy and safety of thrombolysis using Tenecteplase (TNK) versus alteplase in acute ischaemic stroke (AIS) patients within 4.5-hour window period. This retrospective study involved the collection of data from consecutive AIS patients who underwent thrombolysis in the Department of Neurology at a tertiary care university hospital, between May 2018 to January 2021. Data including clinical history, neurological assessment using modified Rankin score (mRS), National Institutes of Health Stroke Scale (NIHSS), brain neuroimaging, treatment, and outcome details were collected. The primary efficacy outcome was the proportion of patients with good functional recovery (mRS of 0-2) at 90 days of follow-up. Total of 42 patients with AIS underwent thrombolysis, of which 19 received alteplase and 23 got TNK. The median (range) onset to door time [120 (20-210) versus 120 (30-210) minutes; P = 0.823] and median (range) onset to needle time [150 (60-255) versus 160 (50-240) minutes; P = 0.779] were comparable in both alteplase and TNK groups, respectively. The primary outcome of good functional recovery (mRS ≤2) at 3 months was observed in more than half the patients in each group and was comparable (P = 0.701). Post-thrombolysis complications including cerebral haemorrhage (symptomatic or asymptomatic) were comparable between the two groups (31.6% vs 30.4%; P = 0.936), except a significantly higher proportion of patients on TNK required mechanical ventilation (10.5% v/s 43.5%; P = 0.019). This study showed a comparable efficacy and safety profile of alteplase and TNK in thrombolysis of AIS throughout the 4.5 hours window period. Moreover, the ease of administration and better pharmacodynamic properties favors tenecteplase.

Update on intravenous lysis treatment : The REVISION trial

To date, no evidence-based treatment for acute non-arteritic central retinal artery occlusion (CRAO) exists. Considering the limited ischemia tolerance of the retina and the results of multiple case series, increasing expectations are directed towards an early intravenous thrombolysis within 4.5 h after CRAO onset. The current literature regards timely retinal reperfusion as the only potentially beneficial therapeutic option to treat non-arteritic CRAO. Available data on the efficacy and safety of thrombolysis in CRAO are presented and discussed. On the basis of these data, the prospective, randomized, double-blind, placebo-controlled REVISION trial (early REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion) will shortly be initiated in 25centers across Germany in order to investigate early intravenous thrombolysis in acute CRAO. The main inclusion criteria of the REVISION trial are outlined, which may help ophthalmologists to identify study candidates and facilitate rapid referral to astudy center. The efficacy of intravenous thrombolysis in acute ischemic stroke is critically time dependent. This may also be assumed in acute CRAO; however, definite evidence still needs to be provided. Until then, the motto "time is retina" should be applied and intravenous thrombolysis should be offered to CRAO patients as part of randomized trials (such as REVISION). According to the current literature, other acute treatment approaches (such as paracentesis) are not indicated.

Thrombolysis combined with acupuncture therapy for acute cerebral infarction: a Meta-analysis of randomized controlled trials

To systematically evaluate the efficacy and safety of thrombolysis combined with acupuncture therapy in the treatment of acute cerebral infarction (ACI) in the light of evidence-based medicine. Randomized controlled trials (RCT) for acupuncture and thrombolysis treatment of acute cerebral infarction published from the inception of databa-ses to March 2020 were searched from PubMed, Cochrane Library, Embase, Web of science, CNKI, Wanfang, VIP, and CBM Database. According to the inclusion and exclusion criteria, two reviewers independently screened the RCTs and extracted the data. The quality of the included literature was evaluated, and the Meta-analysis was performed by using Revman 5.3 software. A total of 330 studies were identified, and 14 RCTs (including 604 cases of the treatment group, 598 cases of the control group) met the inclusion criteria. The Meta-analysis showed that the thrombolysis combined with acupuncture therapy was better than acupuncture therapy alone in the clinical effective rate (risk ratio ［RR］=1.19, 95% confidence interval ［CI］ ［1.13, 1.25］), NIHSS score (mean difference ［MD］=-3.51, 95% CI ［-4.54, -2.48］), BI index (MD=12.26, 95% CI ［8.07, 16.46］), and in lowering C-reaction protein levels (MD=-3.99, 95% CI ［-4.35, -3.63］). The rate of complete recanalization (RR = 1.20, 95% CI ［1.00, 1.44］), adverse reaction (RR = 0.76, 95% CI ［0.41, 1.41］) and hemorrhagic conversion (RR = 0.72, 95% CI ［0.14, 3.62］) was not statistically significant. The current effective evidence shows that acupuncture has certain advantages in improving the therapeutic effect and safety of thrombolysis in the treatment of ACI patients.

Clinical outcomes of very elderly patients treated with ultrasound-assisted catheter-directed thrombolysis for pulmonary embolism: a systematic review.

Pulmonary embolism (PE) is a significant cause of death in the very elderly (≥ 75years) population. Ultrasound-assisted catheter-directed thrombolysis (USCDT) emerges to improve thrombolysis safety and efficacy. However, outcomes in very elderly patients are unknown, as randomized controlled trials exclude this population. Recently, we demonstrated acute kidney injury (AKI) and ischemic hepatitis in an octogenarian intermediate-risk PE patient treated with USCDT. Considering the lack of evidence, we undertook a systematic review to evaluate the clinical outcomes in very elderly PE patients treated with USCDT. We searched for very elderly PE patients treated with USCDT from 2008 to 2019. Additionally, we conducted another systematic review without age restriction to update previous evidence and compare both populations. We also did an exploratory analysis to determine if thrombolysis was followed based on current guidelines or impending clinical deterioration factors. We identified 18 very elderly patients (age 79.2, 75-86), mostly female and with intermediate-risk PE. We found an intracranial hemorrhage (ICH), and a right pulmonary artery rupture. Additionally, two significant bleedings complicated with transient AKI, and one case of AKI and ischemic hepatic injury. The patients who survived all had clinical and echocardiographic in-hospital improvement. Despite low rt-PA doses, ICH and major bleeding remain as feared complications. Thrombolysis decision was driven by impending clinical deterioration factors instead of international guideline recommendations. Our data do not suggest prohibitive risk associated with USCDT in very elderly intermediate and high-risk PE patients. Despite long-term infusions and right ventricular dysfunction, AKI and ischemic hepatic injury were infrequent.

Abstract 1: Thrombolytic Therapy for ‘Wake-Up Stroke’ - A Systematic Review and Meta-Analysis

Introduction: Twenty-five percent of strokes are detected upon awakening (‘wake-up strokes’; WUS) and are not amenable to thrombolytic therapy via existing time-based treatment approaches. We performed a systematic review and meta-analysis of the efficacy and safety of thrombolysis in patients with WUS using imaging-based selection algorithms. Methods: This systematic review was registered through PROSPERO (CRD42020151552). We searched PubMed, Web of Science, and Scopus between January 1, 2006 and April 30, 2020 for controlled trials and observational cohort studies (prospective or retrospective), in which adults with WUS were administered thrombolysis after MR- or CT-based imaging. Our primary outcome was recovery (mRS 0-2) at 90 days and our secondary outcome was symptomatic intracranial hemorrhage (sICH). We assessed risk of bias using the Cochrane Risk of Bias 2.0 and ROBINS-I tools. Results: We included 16 studies that enrolled a total of 14,017 patients. Sixty-one percent of patients receiving tPA achieved a functional recovery at 90 days (95% CI: 51% to 70%; 12 studies), with a relative risk (RR) of recovery of 1.21 compared with patients not receiving tPA (95% CI 1.01 to 1.46; 4 comparative studies). As shown in Figure 1, 3% of patients receiving tPA in the treated WUS stroke group experienced sICH, an RR of 4.0 (95% CI 2.85-5.61) compared with patients not receiving tPA. On meta-regression, advancing age was negatively associated with the RR of recovery (p&lt;0.001) and there was a trend that increased NIHSS was associated with the RR of sICH (p=0.083). Conclusions: In patients with WUS, thrombolysis is associated with functional recovery and with a low risk of sICH. This risk is comparable to the sICH rate from tPA-treatment of stroke utilizing the standard protocol timeframe (2.4% in ECASS III). Thrombolysis should be considered in the treatment of WUS in patients with favorable neuroimaging.

Clinical characteristics and outcomes of combined thrombolysis and anticoagulation for pediatric and young adult lower extremity and inferior vena cava thrombosis

Effective treatment for acute, extensive, symptomatic lower extremity (LE) thrombosis involves thrombolysis in addition to anticoagulation. There is limited available data on the outcomes and safety of thrombolysis to help guide its use in pediatrics and young adults. A retrospective study of children and young adults (<21 years of age) that received catheter directed thrombolysis (CDT) for LE and inferior vena cava (IVC) thrombosis was performed over a 5-year span at a pediatric tertiary care center. A total of 29 patients were identified for inclusion in the study, 76% (n = 22) received overnight CDT while 24% (n = 7) received tissue plasminogen activator as a bolus dose during a single interventional procedure. The median age of the cohort was 15.8 years (range 0–19.1). All patients were treated with a course of therapeutic anticoagulation. The thromboses represented were extensive, with 93% (n = 27) being occlusive and affecting multiple venous segments. Thrombus resolution occurred in 35% (n = 10) of patients. Rivaroxaban use (p < 0.01) during the course of anticoagulation and estrogen-containing hormonal therapy (p = 0.01) use prior to diagnosis were associated with thrombus resolution, while Hispanic ethnicity (p = 0.06) had a trend toward thrombus persistence. There were one major and 3 minor bleeding events that occurred as complications of thrombolysis and no treatment related deaths. This study provides baseline information that can be used to help guide clinicians treating similar patients and suggests the need to develop an improved, uniform treatment approach for superior resolution rates.

Efficacy and safety of thrombolysis for acute ischemic stroke with atrial fibrillation: a meta-analysis

BackgroundThe efficacy and safety of intravenous thrombolysis (IVT) for acute ischemic stroke with atrial fibrillation (AF) is still controversial.MethodsWe conducted a meta-analysis of all relevant studies, retrieved through systematic search of PubMed, Embase, and Cochrane databases up to December 31, 2019. Modified Rankin Scale (mRS) scores of 0–1 at 90 days, mRS of 0–2 at 90 days, overall mortality, and incidence of symptomatic intracranial hemorrhage (sICH) were collected as outcome measures. Fixed- and random-effects meta-analytical models were applied, and between-study heterogeneity was assessed.ResultsA total of 8509 patients were enrolled in 18 studies. A comparison of IVT treatment in AF versus non-AF patients showed that AF was associated with a significantly lower proportion of patients with mRS of 0–1 (24.1% vs. 34.5%; OR 0.59; 95% CI 0.43–0.81; P < 0.001), mRS of 0–2 (33.6% vs. 47.8%; OR 0.55; 95% CI 0.43–0.70; P < 0.001), as well as significantly higher mortality (19.4% vs. 11.5%; OR 2.05; 95% CI 1.79–2.36; P < 0.001) and higher incidence of sICH (6.4% vs. 4.1%; OR 1.60; 95% CI 1.27–2.01; P < 0.001). A comparison of AF patients who were subjected or not to IVT showed that thrombolysis carried a higher risk of sICH (5.7% vs. 1.6%; OR 3.44; 95% CI 2.04–5.82; P < 0.001) and was not associated with a better prognosis. Subgroup analysis in prospective studies also suggested a poorer functional prognosis and higher mortality in AF patients treated with IVT compared with those who did not receive IVT. Some heterogeneity was present in this meta-analysis.ConclusionsAcute IS patients with AF had worse outcomes than those without AF after thrombolytic therapy, and had a higher incidence of sICH after thrombolysis than those without thrombolysis. Thrombolysis in ischemic stroke patients with AF should be carefully considered based on clinical factors such as NIHSS score, age, and the type of AF.

Early Electroacupuncture Extends the rtPA Time Window to 6 h in a Male Rat Model of Embolic Stroke via the ERK1/2-MMP9 Pathway

Background. Recombinant tissue plasminogen activator (rtPA) is the only recommended pharmacological treatment for acute ischemic stroke, but it has a restricted therapeutic time window. When administered at time points greater than 4.5 h after stroke onset, rtPA disrupts the blood-brain barrier (BBB), which leads to serious brain edema and hemorrhagic transformation. Electroacupuncture (EA) exerts a neuroprotective effect on cerebral ischemia; however, researchers have not clearly determined whether EA increases the safety of thrombolysis and extends the therapeutic time window of rtPA administration following ischemic stroke. Objective. The present study was conducted to test the hypothesis that EA extends the therapeutic time window of rtPA for ischemic stroke in a male rat model of embolic stroke. Methods. SD rats were randomly divided into the sham operation group, model group, rtPA group, EA+rtPA group, and rtPA+MEK1/2 inhibitor group. An injection of rtPA was administered 6 h after ischemia. Rats were treated with EA at the Shuigou (GV26) and Neiguan (PC6) acupoints at 2 h after ischemia. Neurological function, infarct volume, BBB permeability, brain edema, and hemorrhagic transformation were assessed at 24 h after ischemia. Western blotting and immunofluorescence staining were performed to detect the levels of proteins involved in the ERK1/2 signaling pathway (MEK1/2 and ERK1/2), tight junction proteins (Claudin5 and ZO-1), and MMP9 in the ischemic penumbra at 24 h after stroke. Results. Delayed rtPA treatment aggravated hemorrhagic transformation and brain edema. However, treatment with EA plus rtPA significantly improved neurological function and reduced the infarct volume, hemorrhagic transformation, brain edema, and EB leakage in rats compared with rtPA alone. EA increased the levels of tight junction proteins, inhibited the activation of the ERK1/2 signaling pathway, and reduced MMP9 overexpression induced by delayed rtPA thrombolysis. Conclusions. EA potentially represents an effective adjunct method to increase the safety of thrombolytic therapy and extend the therapeutic time window of rtPA administration following ischemic stroke. This neuroprotective effect may be mediated by the inhibition of the ERK1/2-MMP9 pathway and alleviation of the destruction of the BBB.

To Thrombolyse or Not to Thrombolyse: Two Years Experience of Thrombolysis of Sub-Massive Pulmonary Embolism in a District General Hospital.

AimsCurrent British Thoracic Society (BTS) guidelines only recommend thrombolysis of pulmonary embolism (PE) in patients who are haemodynamically compromised. Newer evidence suggests a mortality benefit for the thrombolysis of sub-massive PE with right ventricular strain. We wanted to assess the outcome and safety of thrombolysis in patients with sub-massive PE in a DGH.MethodsThe notes for patients with sub-massive PE and thrombolysis from a two-year period were reviewed. Evidence of right ventricular strain and myocardial necrosis based on bedside echocardiography, computed tomography (CT) scan and troponin T were indications for thrombolysis.ResultsA total of 22 patients had thrombolysis of PE in the study period (56±14 years). Fourteen patients were classified as sub-massive PE (55±15 years). Out of eight patients who had thrombolysis of massive PE (58±14 years), three were initially classified as sub-massive PE but deteriorated within the next 48 hours and became haemodynamically unstable. In all patients, the diagnosis was confirmed with a CT pulmonary angiography (CTPA).Mean troponin was 82 in the sub-massive PE group and 102 in the massive PE group. The clinical condition and haemodynamic of patients improved rapidly within a few hours after thrombolysis.Post-thrombolysis echocardiography was performed, 17 patients had normal right ventricles with normal pulmonary arterial pressures.ConclusionThrombolysis of sub-massive pulmonary embolism is feasible in a district general hospital and seems to be a safe procedure, particularly in younger patients. It results in rapid improvement in the clinical condition of patients with a small incidence of bleeding complications.