Dose Of Tissue Plasminogen Activator Research Articles

Treatment outcome of bridge mechanical thrombectomy with different IV-tPA dosages in the standard and extended time window in real-world practice.

Differences of treatment outcome between full or reduced dose of tissue plasminogen activator (tPA) for bridge mechanical thrombectomy (MT) in the extended time window have not been clearly established. We aimed to present real-world results of bridge MT with different tPA dosages in the standard and extended windows. Patients with anterior circulation stroke treated with MT between 2017 and 2021 at two stroke referral centers were retrospectively reviewed. Bridge MT with tPA were categorized as full (0.9mg/kg) or reduced (<0.9mg/kg) dose. Standard window (SW) cohort was defined as MT performed within 6h of acute ischemic stroke onset, while those beyond 6h as the extended window (EW) cohort. 90days Modified Rankin Scale (mRS) score, technical treatment success, in-hospital mortality, and post-treatment hemorrhage were analyzed. A total of 423 patients met the inclusion criteria, 218 of which treated in the SW, while 205 treated in the EW. Within the SW cohort, the full-dose tPA group demonstrated a higher proportion of good functional outcome (GFO) at 90days (mRS0-3) versus reduced (49% vs 21%, p = 0.0358). The overall GFO of SW was higher than that of the EW cohort (33% vs 20%, p = 0.0480). Within the EW cohort, GFO was similar between full and reduced dose groups. Successful reperfusion rate was lower in SW versus EW cohorts (39% vs 58%, p = 0.0199). In real-world practice, the GFO of bridge MT is better than MT alone. The tPA dosage is not a determining factor of GFO in EW MT.

Effectiveness and safety of half-dose thrombolysis in intermediate-high risk pulmonary embolism: a single centre experience

Abstract Funding Acknowledgements None. Introduction According to current guidelines, full-dose systemic thrombolysis for pulmonary embolism (PE) is limited to patients either classified as high risk or presenting intermediate risk with hemodynamically instability. As evidenced by recent clinical trials, "low" half-dose (50 mg) tissue plasminogen activator (HDrtPA) appears to offer a safe, effective alternative with a low bleeding risk, especially if catheter directed therapies are not available. Purpose we aimed to evaluate if HDrtPA in intermediate-high risk PE could improve right ventricular (RV)-arterial coupling by means of TAPSE/PAPs ratio, right ventricular basal dimensions in 4 chambers (RVD1), and tricuspid velocity (TV) between admission and discharge, exploring eventual associated bleeding risk. Methods we retrospectively analized 90 intermediate-high risk PE patients consecutively admitted to our intensive cardiac care unit between January 2016 and May 2023. Diagnosis was achieved by computed tomography in all cases. All patients underwent echocardiographic assessment upon admission and at discharge along with baseline lab values. HDrtPA patients (Group A, n=28) received low-dose thrombolytic therapy (0,6 mg/kg maximum 50 mg in 1 hour) combined with unfractionated heparin. Standard anticoagulation patients (Group B) included patients exclusively treated with parenteral anticoagulants. Primary endpoint was echocardiographic improvement of RV-arterial coupling (TAPSE/PAPS), and of pulmonary pressures (tricuspid velocity, TV) and right ventricular basal dimension (RVD1) between admission and dis-charge in the two treatment arms. To perform this analysis, linear regression models with Inverse Probability Weighting (IPW) propensity scores were used. Secondary endpoint was presence of mayor or minor bleeding between groups, and a descriptive analysis of mortality due to paucity of events. Results in the whole population mean age was 73.48 ± 12.49 (mean ± sd) and n=43 (47.8%) were males. Between admission and discharge, group A (HDrtPA) had an improvement of TAPSE/PAPs (+0.16, p=0.05, CI 95%: -0.002; 0.325), of RVD1 (-6.00 mm, p &amp;lt;0.01, CI 95%: -2.59; 9.41). Reduction of TV values (-0.45 m/s, p=0.108, CI 95%: -1.02; 0.10) was not statistically significant at IPW propensity score, but deserves further investigations. No significant increase of major bleedings were recorded between two groups (Group A: 1/28 3.5%, Group B: 0/52 0%) with an acceptable number of minor, non fatal bleedings (Group A: 7/28: 25%, Group B 1/62 1.6%). Death occurred in 3 patients in group A (10%) and 1 patient in group B (1.6%). Conclusion half dose of tissue plasminogen activator (HDrtPA) offer a promising alternative to anticoagulation alone therapy in selected patients with high-intermediate risk pulmonary embolism. In our experience, this approach seems to acutely improve RV-arterial coupling and right ventricular dimensions, without an increase of major bleeding risk.

Low‐dose tissue plasminogen activator is safe and effective in treating major intracardiac thrombosis in liver transplant recipients

AbstractBackgroundMajor intracardiac thrombosis is an uncommon event during liver transplantation and has a high mortality rate. Given concerns for hemorrhage in liver transplantation with higher doses, low‐dose tissue plasminogen activator has been proposed as a treatment that rapidly leads to localized clot lysis and resolution of right ventricular failure.MethodsThis is a retrospective study using a prospectively collected database at the University of California at Los Angeles of liver transplant recipients from 2004‐2021. Adult patients who received tissue plasminogen activator for intracardiac thrombosis detected on transesophageal echocardiography were included.ResultsOut of 3236 liver transplants from 2016 to 2021, 11 liver transplant recipients were treated with intravenous low‐dose tissue plasminogen activator for major intracardiac thrombosis. The TPA dose range was 1–2.5 mg with three patients receiving more than one dose. All patients had severe hemodynamic instability. 90.9% of patients had right ventricular failure and 63.6% had cardiac arrest. After administration of low‐dose tissue plasminogen activator, 100% of patients had clinical improvement, clot resolution, and intraoperative survival, with 91% survival at 6 months post‐transplant. Adverse events included two patients with abdominal bleeding requiring re‐exploration and three patients having new intracranial hemorrhage which self‐resolved.ConclusionsLow dose tissue plasminogen activator was effective in treating major intracardiac thrombosis in our group of patients. Major complications included a limited number of hemorrhagic events.

Plasma Fibrinogen Change as a Predictor of Major Bleeding During Catheter-Directed Thrombolysis

Our primary objective was to determine the relationship between plasma fibrinogen levels (PFLs) and major bleeding complications during catheter-directed thrombolysis, including final, nadir, and change over time. Furthermore, we sought to evaluate additional predictors of bleeding outcomes, including duration of lysis and total dose of tissue plasminogen activator received. In this multicenter retrospective cohort study, we reviewed all patients undergoing catheter-directed thrombolysis between January 2016 and August 2021. Patients undergoing thrombolysis for management of peripheral arterial or venous thromboses, as well as for submassive pulmonary embolism, were included. We examined the relationships between PFLs during catheter-directed lysis and the incidence of major bleeding-that is significant hemorrhage requiring transfusion, intracranial hemorrhage, or hemorrhage requiring adjunctive procedures. We also examined the duration of lysis and total lytic agent dose received to assess for association with major bleeding. A total of 438 patients underwent catheter-directed lysis from January 1, 2016 through August 21, 2021, with a major bleeding rate of 16%. Patients who experienced major bleeding were more likely to be older (P=0.022), experience in-stent thrombosis (P=0.041), or have thrombosis in a lower extremity vessel (P=0.011). There was no association between the incidence of major bleeding and a nadir PFL of <150mg/dL (P=0.194). Those who experienced major bleeding complications had a significantly greater decrease in PFL from baseline to nadir. This was true for both absolute (P=0.029) and relative (P=0.034) PFL decrease. Only percent decrease remained a significant predictor when adjusting for age, thrombosis type, and thrombosis location (P=0.041). The PFL changes that were the best predictors of major bleeding complications were an absolute decrease of 146mg/dL, or a relative decrease of 47%, giving a sensitivity and specificity of 71% and 48%, respectively. If neither were true, the negative predictive value for major bleeding was 89% regardless of absolute PFL. In this large, multicenter cohort, there does not appear to be an association between absolute PFL and major bleeding during catheter-directed lysis. Specifically, the typical absolute threshold of < 150mg/dL was not an independent predictor of major bleeding. There was an association between percent-change in plasma fibrinogen and major bleeding, which aligns with the underlying physiologic mechanism of fibrinogen degradation coagulopathy. Applying a so-called "50-150 Rule" to catheter-directed lysis may decrease bleeding complications. That is, continued lysis should be re-evaluated if PFL drops by≥150mg/dL or by≥50% from baseline regardless of absolute PFL.

Pharmacomechanical Catheter-Directed Thrombolysis With the Bashir Endovascular Catheter for Acute Pulmonary Embolism: The RESCUE Study

BackgroundCatheter-directed thrombolysis (CDT) has been associated with rapid recovery of right ventricular (RV) function. The Bashir catheter was developed for enhanced thrombolysis in large vessels such as the pulmonary arteries (PAs) with lower doses of tissue plasminogen activator (tPA). ObjectivesThe aim of this study was to evaluate the efficacy and safety of tPA infused using a pharmacomechanical (PM) CDT device called the Bashir endovascular catheter in patients with intermediate-risk acute pulmonary embolism (PE). MethodsPatients with symptoms of acute PE with computed tomographic evidence of RV dilatation were enrolled. The Bashir catheter was used to deliver 7 mg tPA into each PA over 5 hours. The primary efficacy endpoint was the core laboratory–assessed change in computed tomographic angiography–derived RV/left ventricular (LV) diameter ratio at 48 hours, and the primary safety endpoint was serious adverse events (SAEs) including major bleeding at 72 hours. ResultsAt 18 U.S. sites, 109 patients were enrolled. The median device placement time was 15 minutes. At 48 hours after PM-CDT, the RV/LV diameter ratio decreased by 0.56 (33.3%; P < 0.0001). PA obstruction as measured by the refined modified Miller index was reduced by 35.9% (P < 0.0001). One patient (0.92%) had 2 SAEs: a retroperitoneal bleed (procedure related) and iliac vein thrombosis (device related). Two other procedure-related SAEs were epistaxis and non–access site hematoma with anemia. ConclusionsPM-CDT with the Bashir endovascular catheter is associated with a significant reduction in RV/LV diameter ratio and a very low rate of adverse events or major bleeding in patients with intermediate-risk acute PE. The notable finding was a significant reduction in PA obstruction with low-dose tPA. (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden [RESCUE]; NCT04248868)

Effect of the interaction between atrial fibrillation and rt-PA dose on the prognosis of acute ischaemic stroke with intravenous thrombolysis

BackgroundThe association between atrial fibrillation (AF) and the prognosis of acute ischaemic stroke (AIS) remains controversial; whether the recombinant tissue plasminogen activator dose influences this association remains poorly understood.MethodsPatients who...

Effect of the interaction between atrial fibrillation and rt-PA dose on the prognosis of acute ischaemic stroke with intravenous thrombolysis.

The association between atrial fibrillation (AF) and the prognosis of acute ischaemic stroke (AIS) remains controversial; whether the recombinant tissue plasminogen activator dose influences this association remains poorly understood. Patients who had an AIS were enrolled from eight stroke centres in China. According to the recombinant tissue plasminogen activator dose, patients treated with intravenous recombinant tissue plasminogen activator within 4.5 hours after symptom onset were divided into a low-dose group (recombinant tissue plasminogen activator <0.85 mg/kg) and a standard-dose group (recombinant tissue plasminogen activator ≥0.85 mg/kg). Patients who had an AIS in the low-dose group and the standard dose group were divided into whether or not they had AF. The main outcomes were major disability (modified Rankin scale (mRS) score 3-5), mortality and vascular events occurring within 3 months. The study included 630 patients who received recombinant tissue plasminogen activator after AIS, including 391 males and 239 females, with a mean age of 65.8 years. Of these patients, 305 (48.4%) received low-dose recombinant tissue plasminogen activator and 325 (51.6%) received standard dose recombinant tissue plasminogen activator. The recombinant tissue plasminogen activator dose significantly influenced the association between AF and death or major disability (p-interaction=0.036). After multivariate adjustment, AF was associated with an increased risk of death or major disability (OR 2.90, 95% CI 1.47 to 5.72, p=0.002), major disability (OR 1.93, 95% CI 1.04 to 3.59, p=0.038) and vascular events (HR 5.01, 95% CI 2.25 to 11.14, p<0.001) within 3 months in patients with standard-dose recombinant tissue plasminogen activator. No significant association was found between AF and any clinical outcome in patients with low-dose recombinant tissue plasminogen activator (all p>0.05). With AF, the mRS score distribution showed a significantly worse shift in patients with standard-dose recombinant tissue plasminogen activator (p=0.016) than in those with low-dose recombinant tissue plasminogen activator (p=0.874). AF may be a strong predictor of poor prognosis in patients who had an AIS receiving standard-dose recombinant tissue plasminogen activator, suggesting that low-dose recombinant tissue plasminogen activator should be administered to patients who had a stroke with AF to improve their prognosis.

Abstract No. 362 Texture analysis of arterial graft thrombus on CT angiography: correlation with age of thrombus and implication on catheter directed thrombolysis

Catheter-directed thrombolysis (CDT) is the widely utilized treatment for patients with acute occlusion of lower extremity arteries and bypass grafts. The success and dose of tissue plasminogen activator (tPA) required is influenced by age of thrombus, which is primarily assessed by clinical parameters. The aim of this study is to investigate the potential role of utilizing quantitative texture analyses in determining the age of thrombus in relation to patients’ clinical profiles, further predicting the dose of required thrombolytic agent.

Acoustic pulse thrombolysis complemented by ECMO improved survival in patients with high-risk pulmonary embolism.

The optimal treatment of high-risk pulmonary embolism (PE) with cardiac arrest is still controversial although various treatment approaches have been developed and improved. Here, we present a serie of patients with high-risk PE showing hemodynamic collapse, who were successfully treated with extracorporeal membrane oxygenation (ECMO) as an adjunct to EKOS™ acoustic pulse thrombolysis (APT). From April 2016 to June 2020, 29 patients with high-risk PE with cardiac arrest were retrospectively included. The mean age was 55.3 ± 9.2 years. A total of 12 (41.3%) patients were female. All patients had cardiac arrest, either as an initial presentation or in-hospital after presentation. All patients exhibited acute symptoms, computed tomography evidence of large thrombus burden, and severe right ventricular dysfunction. Primary outcome was all-cause 30-day mortality. Twenty-two patients survived to hospital discharge, with a mean intensive care unit stay of 9.9 ± 1.6 days (range: 7-22 days) and mean length of hospital stay of 23.7 ± 8.5 days (range: 11-44 days). Six patients died from refractory shock. Ninety-day mortality was 24.1% (7/29). The Mean ECMO duration was 3.5 ± 1.1 days and the mean RV/LV ratio decreased from 1.31 ± 0.17 to 0.92 ± 0.11 in patients who survived to discharge. The mean tissue plasminogen activator dose for survivor patients was 20.5 ± 1.6 mg. Patients with high-risk pulmonary embolism who suffer a cardiac arrest have high morbidity and mortality. APT complemented by ECMO could be a successful treatment option for the patients who have high-risk PE with circulatory collapse.

Novel Pharmacomechanical Thrombolysis for Treating Intermediate-Risk Acute Pulmonary Embolism: The Bashir Endovascular Catheter.

Novel Pharmacomechanical Thrombolysis for Treating Intermediate-Risk Acute Pulmonary Embolism: The Bashir Endovascular Catheter.

Intrapulmonary Artery Thrombolysis in Acute Pulmonary Embolism: Case Series from King Chulalongkorn Memorial Hospital Experience

Acute pulmonary embolism (PE) is a life-threatening condition. In patient who has contraindication for systemic thrombolysis and inappropriate for surgical embolectomy, there is a role of catheter interventions. However, the data are limited. The aim of the present report was to assess a role of intrapulmonary artery thrombolysis bolus in acute PE. A retrospective review of the use of intrapulmonary artery thrombolysis in acute PE. The data were collected from 14 patients with massive or submassive PE who had contraindication or inappropriate for systemic thrombolysis and unsuitable for surgical embolectomy. After intrapulmonary thrombolysis was given, patients were followed clinically and hemodynamically until discharged and after 1 month. Pulmonary pressure was collected at pre and post intervention. Of the 14 patients (age 59±19 years, 78.6% female), 86% were diagnosed as submassive PE. Mean dose of tissue plasminogen activator (rt-PA) was 28±14 mg given as bolus and continuous infusion (19±10 hours). One patient died after completion of intrapulmonary infusion rt-PA at day 90, which did not relate to PE and the treatment. After intervention, mean PA pressure was significantly reduced from 32.3±6.0 to 21.0±4.3 mmHg (p&lt;0.001). Three patients (21%) had minor bleeding (hematoma at access site). The present case series showed that intrapulmonary infusion of rt-PA was effective and safe in patient with massive and submassive PE who had contraindication or inappropriate to systemic thrombolysis or inoperable surgical thrombectomy. Keywords: Acute pulmonary embolism; Intrapulmonary thrombolysis; Tissue plasminogen activator; Surgical thrombectomy

A Case Report on Concurrent Stroke and Myocardial Infarction

Concurrent myocardial infarction and acute cerebral infarction is a rare and poorly studied phenomenon that presents a challenge to treat as both conditions are life threatening with narrow therapeutic windows. We present the case of a 70 year old female who presented with symptoms concerning for stroke. However, an electrocardiogram revealed she was also having an acute myocardial infarction. The decision was made to treat the stroke with intravenous tissue plasminogen activator. Unfortunately, the patient ultimately decompensated and died. There are many proposed etiologies of this phenomenon including cardiac thrombi leading to concurrent acute myocardial infarction and cerebral infarction, a primary myocardial infarction leading to a cerebral infarction, and a primary cerebral infarction leading to an acute myocardial infarction. Treatment options include simultaneous mechanical thrombectomy and percutaneous coronary intervention in a cardiac catheterization laboratory, or treating with the intravenous tissue plasminogen activator dose for a cerebral infarction and then potentially also proceeding to percutaneous coronary intervention. Ultimately, the management of this situation will depend on the patient’s specific situation including the type of stroke, the extent of irreversible tissue damage, and the hospital’s available resources. A randomized controlled study is difficult because of the rare occurrence of both presentations and a systematic review of the available literature may provide physicians with better insight as to how to approach a simultaneous acute myocardial infarction and acute cerebral infarction.

Efficacy and Safety of Different Dosage of Recombinant Tissue-type Plasminogen Activator (rt-PA) in the Treatment of Acute Pulmonary Embolism: A Systematic Review and Meta-analysis.

Reperfusion therapies are recommended for patients with hemodynamic instability or high-risk acute pulmonary embolism (PE). Lower doses of tissue plasminogen activator (rt-PA) could be considered to improve bleeding complications. The aim of this study was to evaluate the efficacy and safety of a reduced dose of rt-PA for the treatment of acute PE, compared with anticoagulation and standard dose. PubMed Central, Scopus, Web of Science and Embase were searched for all relevant randomized studies and prospective observational studies that compared reduced dose of rt-PA with anticoagulation alone or standard dose of rt-PA in patients with acute PE. The risk ratios (RR, with 95% CI) were calculated according to the value of I2. Outcomes were described as bleeding events, all-cause death, and recurrence of PE. Thirteen articles, including four observational studies (4223 patients) and nine RCTs (780 patients), were included. In comparing reduced dose of rt-PA with anticoagulant, a greater incidence of total bleeding events in low dose was showed (RR, 5.08 (95% CI, (1.39–18.6), I2 = 0.0%). In the standard dose rt-PA vs. reduced dose, there was a greater incidence of total bleeding events in the standard dose of rt-PA, RR 1.48 (95% CI, (1.00–2.19), I2 = 0.0%) was shown. There were no statistical differences in recurrent PE or all-cause mortality. It concluded that in the absence of the benefit of a standard dose of rt-PA in comparison with dose reduction, a reduced dose of rt-PA showed a lower rate of total bleeding events and similar efficacy regarding mortality and PE recurrence rate.

Evaluation of the Benefit of Extended Catheter-Directed Thrombolysis with Serial Angiography for Acute Pulmonary Embolism

PurposeTo evaluate whether extended catheter-directed thrombolysis (CDT) with repeat visits to the angiography suite provide added benefit in treatment of acute pulmonary embolism (PE). Materials and MethodsThis was a retrospective review of CDT procedures performed for acute PE in 156 patients (age 56.1 y ± 15.3, 46.2% women) between 2009 and 2019. All patients underwent at least 1 follow-up visit to the angiography suite for evaluation of pulmonary artery pressure (PAP) and thrombus burden (Miller score) before termination (111/156, 71.2%) or continuation of CDT (45/156, 28.8%). ResultsPatients who had CDT extended beyond the first follow-up visit required a higher total dose of tissue plasminogen activator (40.7 mg ± 14.3 vs 22.6 mg ± 9.9, P < .001) to achieve a similar final Miller score (6.4 ± 3.8 vs 7.6 ± 3.9, P = .1) and a similar reduction in systolic PAP (−14.4 mm Hg ± 10.2 vs −12.6 mm Hg ± 11.9, P = .6). The initial Miller scores were similar in both groups (19.7 ± 5.8 vs 19 ± 4, P = .4) but were significantly higher during the first follow-up visit (after 18 hours ± 5.5 vs 20 hours ± 4.8, P = .06) in patients requiring multiple follow-up visits (12.2 ± 5 vs 7.6 ± 3.9, P < .001). Multiple regression analyses identified heart rate > 100 beats/min and systolic PAP > 55 mm Hg as associated with the need for extended CDT. Extended CDT did not result in a higher hemorrhagic complication rate (1/45 vs 6/111, P = .7). ConclusionsPatients presenting with higher heart rates and systolic PAP may benefit from extended CDT to achieve similar reductions in PAP and thrombus burden, without clear added risk of hemorrhage.

Utilization and outcomes with low dose tissue plasminogen activator as intravenous thrombolytic therapy for ischaemic stroke at Aga Khan University Hospital, Karachi: a retrospective analysis.

To determine the utilisation of intravenous tissue plasminogen activator at a certain dose for ischaemic stroke thrombolysis and to compare the outcomes with those of a different dosage mentioned in literature. The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised medical records from January, 2007, to October, 2016, of all patients having received intravenous tissue plasminogen activator for ischaemic stroke thrombolysis. Primary safety outcome variables included symptomatic intracerebral haemorrhage after the start of treatment (0.6mg/kg) and death within three months as per the modified Rankin scale 6. Secondary efficacy outcome variable was functional independence as per modified Rankin scale 0-2 at three months. The outcomes were compared with those mentioned in literature with a dose of 0. 9mg/kg. Of the 79 patients, 52 (66%) were male and 27 (34 %) were female. Median pre-treatment tissue plasminogen activator score was 12 (interquartile range: 8-15). Overall utilisation of t-PA remained at 1.7%. Symptomatic intracerebral haemorrhage was not seen in our cohort while it was seen in 107 (1.7%) patients at the higher dose. Using another definition, it was seen in 3 (3.8%) patients versus 468 (7.3%) patients at the higher dose. Functional independence was seen in 40 (50.6%) patients at three months compared to 3362 (54.8%) patients at the higher dose. Low-dose intravenous thrombolytic therapy for ischaemic stroke patients was found to be safe and efficacious, and yielded comparable results with those obtained at a higher dose..

Real-World Outcomes of EKOS Ultrasound-Enhanced Catheter-Directed Thrombolysis for Acute Limb Ischemia

Ultrasound-enhanced catheter-directed thrombolysis (UET) using the Ekosonic® Endovascular System device for acute, peripheral arterial ischemia has been purported in clinical trials to accelerate the fibrinolytic process to reduce treatment time and lytic dosage. We aim to describe outcomes of UET in a real-world clinical setting. We performed a retrospective review of all patients undergoing UET for acute limb ischemia at a single institution. Data collected included patient demographics, procedural details, and 30-day and 1-year outcomes. The primary endpoints for analysis were major adverse limb events (MALEs; reintervention and/or amputation) and mortality within 30-days and 1-year. Secondary endpoints included technical success, use of adjunctive therapies, and postoperative complications. A total of 32 patients (mean age 67.4±14.9years; 25% women) underwent UET for acute limb ischemia between 2014 and 2018. The Rutherford Acute Limb Ischemia Classification was Rutherford (R) 1 in 56.3%, R2a in 31.3%, and R2b in 12.5%. Etiology was thrombosis of native artery in 12.5% of patients, prosthetic bypass in 31.3%, autogenous bypass in 6.3%, and stented native vessel in 50.0%. Mean duration of thrombolytic therapy was 22.2±11.3hr, and mean tissue plasminogen activator dose was 24.5±15.3mg. MALEs occurred in 16.7% of patients within the first 30 days and 38.9% experienced a MALE by 1 year. Limb salvage at 30 days and 1 year was 93.8% and 87.5%, respectively. Ipsilateral reintervention was required in 12.5% of patients within 30days and 37.5% of patients within 1year. Overall mortality was 6.2% at 30 days and 13.5% at 1 year. In-line flow to the foot was re-established in 90.6% of patients, with a significant improvement in preoperative to postoperative ankle-brachial index (0.31±0.29 vs. 0.78±0.34, P<0.001) and number of patent tibial runoff vessels (1.31±1.20 vs. 1.96±0.86, P<0.001). There was no significant difference in revascularization success between occluded vessel types. All but one patient required adjunctive therapy such as further thromboaspiration, stenting, or balloon angioplasty. Major bleeding complications occurred in 3 patients (9.4%), including 1 intracranial hemorrhage (3.1%). UET with the EKOS device demonstrates acceptable real-world outcomes in the treatment of acute limb ischemia. UET is generally safe and effective at re-establishing in-line flow to yield high limb salvage rates. However, UET is associated with a high rate of reintervention. Further investigation is needed into specific predictors of limb salvage and need for reintervention, as well as cost-efficacy of this technology compared with that of traditional methods.

TPA Use for Central Line De-Occlusion and Its Relationship to Symptomatic Venous Thromboembolism in Pediatric Leukemia Patients

Introduction: Venous thromboembolism (VTE) is a known complication of pediatric leukemia with reported incidence ranging widely from 1.5-40%. It is associated with significant morbidity including loss of venous access, post thrombotic syndrome, and thrombosis recurrence or embolization. Increased risk of VTE in these patients is often multifactorial. There are currently no standard guidelines for VTE prophylaxis in pediatric leukemia patients, and it is unclear which patients are at highest risk. Identifying potential markers for patients at risk for VTE could be helpful for guiding prophylaxis practices and ultimately decreasing rates of VTE in these children. Thrombolytic agents are commonly used to treat catheter obstruction by breaking down fibrin that forms within the catheter. Therefore, we hypothesize that patients requiring more tissue plasminogen activator (TPA) for treatment of catheter obstruction may be at higher risk of developing fulminant thromboses. Therefore, the primary objectiveof this study is to determine the association between central line clearance with TPA and development of symptomatic VTE (sVTE) in pediatric leukemia patients. Methods: This is a multi-center,retrospective cohort study of patients under 21 years old with a central line (CVC), including peripherally inserted central catheters (PICC), who began treatment at Weill Cornell Medicine (WCM) or Memorial Sloan Kettering Cancer Center (MSKCC) from January 2012-December 2015 for newly diagnosed or relapsed leukemia. Patients were excluded if they had a prior VTE, or an incidental VTE was identified. Transplant and CAR-T -cell patients were excluded, as were those who transferred into the institution over 30 days from start of treatment. Data collected included demographics, disease-specific information (including type of leukemia, treatment regimen, and CVC details), dates of TPA administration, and details of sVTE. Data analysis was performed with Fisher's exact test andWilcoxon rank-sum test. Results: A total of 96 patients with leukemia were included. The median age was 6.5 years (Q1, Q3: 3.15-15.05 years), and 55% (n=53) were male. 78% (n=75) were new diagnoses. Acute lymphoblastic leukemia (ALL; 72%, n=69) was most common, followed by acute myelogenous leukemia (AML; 25%, n=24), and mixed lineage leukemias (3%, n=3). There were no significant differences between gender, age, type of leukemia, or TPA use between the two centers. The overall incidence of sVTE over the 4-year period in this cohort was 6% (6/96). At the time of thrombosis, five of the six patients had a PICC line in place and one patient had a mediport (Table 1). Four sVTE patients were diagnosed with ALL. Four of the thromboses were line-associated, one was a sinus venous thrombosis, and one was an inferior vena cava thrombus. Five of the six sVTEs were diagnosed at WCM. There was no association found between use of TPA for line de-occlusion and development of sVTE (OR 0.55, CI 0.07-6.57, p=0.61) or between number of TPA doses needed and development of sVTE (p=0.830). The patients who developed sVTE were significantly older than those who did not develop sVTE (Figure 1, p=0.048). There was no significant difference between gender and development of sVTE. A significant difference (p &lt;0.05) was seen when analyzing the association between PICC line and development of sVTE, however the sample size was too small to draw formal conclusions. Conclusions: In our cohort, neither TPA use for line occlusion nor the number of TPA doses was predictive of sVTE development. This may be due to the small sample size and low number of sVTE events. Single center analysis of data from WCM, however, previously indicated a significant association between TPA use and development of thrombosis in their patients. Given the increased use of PICC lines at WCM, this raises the question of whether TPA use may be predictive in patients who have PICC lines. Our data are consistent with previous pediatric studies, which found older age to be a risk factor for thrombosis. Analysis of a larger cohort of patients is necessary to further investigate our hypothesis. Given the importance of preventing sVTE in pediatric leukemia patients, further prospective studies are needed to investigate potential predictors of thrombosis in this population. Disclosures Cooley: off-label: Other: drug use.

Results of a multinational survey of diagnostic and management practices of thromboembolic pulmonary embolism in children

IntroductionThe incidence of thromboembolic (TE)-pediatric pulmonary embolism (PPE) is increasing. We sought to evaluate current practice patterns and gaps in the management of TE-PPE. Materials and methodsAfter Institutional Review Board approval, SurveyMonkey® questions were sent to members of the Pediatric/Neonatal Thrombosis and Hemostasis Subcommittee, of the International Society on Thrombosis and Haemostasis and the Hemostasis and Thrombosis Research Society. ResultsOf 442 members of the two groups, 134 (30%) responded, and 125 (28%) complete responses were analyzed. Eighty percent practiced at a pediatric facility, 88% at academic centers, and 59% in the USA. Computed tomography pulmonary angiography (CTPA) was the preferred diagnostic modality (89%). D-dimer testing was variably used; 22% used clinical diagnostic prediction models and 8% had specific clinical care pathways for TE-PPE management. Prognostic stratification models were used to guide therapy by 4%. Indications for thrombolytic therapy varied considerably; 40% had a standardized protocol for thrombolysis, employing various modalities (45% systemic, 25% catheter-directed, 19% pharmaco-mechanical) and tissue plasminogen activator dose intensities. Duration of anticoagulation was variable with 58% prescribing anticoagulation for duration of >3 months–6 months; 61% followed for long-term adverse outcomes. ConclusionThis multinational survey of thrombosis/hemostasis specialists mainly based at pediatric academic centers demonstrates that antithrombotic management of TE-PPE (including duration of anticoagulation and use/non-use of thrombolysis) varies considerably. Furthermore, standardized care pathways to facilitate acute evaluation and management decisions are in place in a minority of centers. These findings help to inform the design of future clinical trials in TE-PPE.

A promising method for the salvage of thrombosed native hemodialysis fistulas: percutaneous ultrasound-guided thrombolytic injection

Background/aim It was aimed to describe the technical aspects and outcomes of percutaneous ultrasound-guided recanalization of thrombosed hemodialysis fistulas by thrombolytic injection.Materials and methods A retrospective review was performed on patients with thrombosed native hemodialysis fistula who were treated using the percutaneous ultrasound-guided thrombolytic agent injection technique at the interventional radiology department. A total of 17 patients [7 women (41.2%) and 10 men (58.8%)] were included in this study. All of the data, including demographic information and clinical findings, were obtained from the patients’ medical records and follow-up form of the procedure.Results The mean fistula age was 5.6 years (range: 1–15 years). The mean diameter of the thrombosed segment was 5.53 cm (2–10 cm). Localization of the thrombi was in the aneurysmal segment at the level of needle insertion in 64.7% (n: 11) of patients, while it was on the venous side of the anastomosis in 35.3% (n: 6). The mean dose of tissue plasminogen activator (tPA) used in all of the sessions was 8.88 mg (5–17 mg). Overall technical success after all of the administrations was 100% and clinical success was 94.1%.Conclusion Percutaneous ultrasound-guided thrombolytic injection in native hemodialysis fistulas is a rapid, practical, repeatable treatment method that is received on an outpatient basis with low risk of bleeding, and prevents unnecessary endovascular interventions or surgical operations.

Enhanced Thrombolysis by Ultrasound-Assisted Catheter-Directed Thrombolysis and Microbubbles in an In Vitro Model of Iliofemoral Deep Vein Thrombosis.

There is a need to improve the efficacy and safety of catheter-directed thrombolysis (CDT) for thrombo-occlusive diseases, and ultrasound-assisted CDT (USAT) is a promising approach. We tested if thrombolysis efficacy of USAT can be improved by adding gaseous microbubbles (MB). We developed an in vitro dynamic overflow model for iliofemoral deep vein thrombosis, and added MB to an USAT system with ultrasound energy and dose of tissue plasminogen activator according to clinical practice. A total of 64 clots (mean baseline weight of 8.23 ± 1.12 g, generated from citrated human whole blood from 7 healthy male volunteers) were randomly assigned to 1 of 4 study protocols of 30 minutes' duration: negative control, CDT, USAT, and USAT + MB.Thrombolysis efficacy was assessed by measuring the change in D-dimer levels in the overflow liquid and the percentage of clot weight reduction. Compared to negative control, change in D-dimer increased by 62% (p = 0.017), 128% (p = 0.002), and 177% (p < 0.001) in the CDT, USAT, and USAT + MB groups, respectively. D-dimer increase was greater in the USAT than in the CDT group (p = 0.014), and greater in the USAT + MB than in the USAT group (p = 0.033). Compared to negative control, percentage of clot weight reduction increased by 123% (p = 0.016), 154% (p = 0.002), and 233% (p < 0.001) in the CDT, USAT, and USAT + MB groups, respectively. Percentage of clot weight reduction was greatest in the USAT + MB group (p < 0.05 compared with all other groups). In conclusion, our in vitro study suggests that the thrombolytic efficacy of USAT in human whole blood clots can be improved by local administration of MB.