Dose Of Tissue Plasminogen Activator Research Articles

IP225. Real-World Outcomes of EKOS Ultrasound-Enhanced Catheter-Directed Thrombolysis for Acute Limb Ischemia

Ultrasound-enhanced catheter-directed thrombolysis (UET) using the EKOS device (EKOS Corporation, Bothell, Wash) for acute peripheral artery ischemia has been purported in clinical trials to accelerate the fibrinolytic process to reduce treatment time and lytic dosage. However, UET performance in a real-world clinical setting has thus far been inadequately described. We performed a retrospective review of all patients undergoing UET for acute limb ischemia at a single institution during a 5-year period. Data collected included patients' demographics, procedural details, and 30-day and 1-year outcomes. Primary outcomes were major bleeding events, limb salvage, and mortality. We identified 32 patients (mean age, 67.4 ± 14.9 years; 25% female) who underwent UET for acute limb ischemia between 2014 and 2018. At presentation, 43.8% were therapeutically anticoagulated. Rutherford acute limb ischemia classification was I in 56.3%, IIa in 25.0%, and IIb in 18.8%. Etiology was thrombosis of native artery in 12.5% of patients, infrainguinal prosthetic bypass in 31.3%, infrainguinal autogenous bypass in 6.3%, and stented native vessel in 50.0%. Mean duration of thrombolytic therapy was 22.2 ± 11.3 hours, and mean tissue plasminogen activator dose was 24.5 ± 15.3 mg. 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 < .001) and number of patent tibial runoff vessels (1.31 ± 1.20 vs 1.96 ± 0.86; P < .001; Fig). There was no significant difference in revascularization success between occluded vessel types: native vessel, 75% success; stented vessel, 93.8%, autogenous bypass, 100%, and prosthetic bypass, 90% (P = .48). Major bleeding complications occurred in three patients (9.4%), including two intracranial hemorrhages (6.3%). Limb salvage at 30 days and 1 year was 93.8% and 87.5%, respectively. Ipsilateral reintervention was required in 37.5% of patients within 1 year. Overall mortality was 6.2% at 30 days and 13.5% at 1 year, and mortality was significantly higher in patients with higher Rutherford class (P = .049). UET with the EKOS device demonstrates acceptable real-world outcomes in the treatment of acute limb ischemia. UET is generally safe, with a low rate of associated hemorrhagic complications, and is effective at re-establishing in-line flow to yield high limb salvage rates. However, UET is associated with a high rate of reintervention within 1 year. Further investigation is needed into specific predictors of limb salvage and need for reintervention as well as cost-efficacy of this technology compared with traditional methods.

Thrombolysis related symptomatic intracranial hemorrhage in estimated versus measured body weight.

Background and aimIn acute ischemic stroke, under- or overestimation of body weight can lead to dosing errors of recombinant tissue plasminogen activator with consequent reduced efficacy or increased risk of hemorrhagic complications. Measurement of body weight is more accurate than estimation of body weight but potentially leads to longer door-to-needle times. Our aim was to assess if weight modality (estimation of body weight versus measurement of body weight) is associated with (i) symptomatic intracranial hemorrhage rate, (ii) clinical outcome, and (iii) door-to-needle times.MethodsConsecutive patients treated with intravenous thrombolysis between 2009 and 2016 from 14 hospitals were included. Baseline characteristics and outcome parameters were retrieved from medical records. We defined symptomatic intracranial hemorrhage according to the European Cooperative Acute Stroke Study (ECASS)-III definition and clinical outcome was assessed with the modified Rankin Scale. The association of weight modality and outcome parameters was estimated with regression analyses.ResultsA total of 4801 patients were included. Five hospitals used measurement of body weight (n = 1753), six hospitals used estimation of body weight (n = 2325), and three hospitals (n = 723) changed from estimation of body weight to measurement of body weight during the study period. In 2048 of the patients (43%), measurement of body weight was used and in 2753 (57%), estimation of body weight. In the measurement of body weight group, an inbuilt weighing bed was used in 1094 patients (53%) and a patient lift scale in 954 patients (47%). In the estimation of body weight group, policy regarding estimation was similar. Estimation of body weight was not associated with increased symptomatic intracranial hemorrhage risk (adjusted odds ratio = 1.16; 95% confidence interval 0.83–1.62) or favorable outcome (adjusted odds ratio = 0.99; 95% confidence interval 0.82–1.21), but it was significantly associated with longer door-to-needle times compared to measurement of body weight using an inbuilt weighing bed (adjusted B = 3.57; 95% confidence interval 1.33–5.80) and shorter door-to-needle times compared to measurement of body weight using a patient lift scale (−3.96; 95% confidence interval −6.38 to −1.53).ConclusionWe did not find evidence that weight modality (estimation of body weight versus measurement of body weight) to determine recombinant tissue plasminogen activator dose in intravenous thrombolysis eligible patients is associated with symptomatic intracranial hemorrhage or clinical outcome. We did find that estimation of body weight leads to longer door-to-needle times compared to measurement of body weight using an inbuilt weighing bed and to shorter door-to-needle times compared to measurement of body weight using a patient lift scale.

Tissue plasminogen activator dose and pulmonary artery pressure reduction in catheter directed thrombolysis of submassive pulmonary embolism.

PurposeThe purpose of this study is to assess the incremental effect of tissue plasminogen activator (t-PA) dose on pulmonary artery pressure (PAP) and bleeding during catheter directed thrombolysis (CDT) of submassive pulmonary embolism (PE).Materials and methodsRecords of 46 consecutive patients (25 men, 21 women, mean age 55±14 y) who underwent CDT for submassive PE between September 2009 and February 2017 were retrospectively reviewed. Mean t-PA rate was 0.7±0.3 mg/h. PAP was measured at baseline and daily until CDT termination. Mixed-effects regression modeling was performed of repeated PAP measures in individual patients. Bleeding events were classified by Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) and t-PA dose at onset.ResultsMean t-PA dose was 43.0±30.0 mg over 61.9± 28.8 h. Mean systolic PAP decreased from 51.7±15.5 mmHg at baseline to 35.6±12.7 mmHg at CDT termination (p<0.001). Mixed-effects regression revealed a linear decrease in systolic PAP over time (β = -0.37 (SE = 0.05), p<0.001) with reduction in mean systolic PAP to 44.8±1.9 mmHg at 12 mg t-PA/20 h, 39.5±2.0 mmHg at 24 mg t-PA/40 h, and 34.9±2.1 mmHg at 36 mg/60 h. No severe, one moderate, and 8 mild bleeding events occurred; bleeding onset was more frequent at ≤24 mg t-PA (p <0.001). One patient expired from cardiopulmonary arrest after 16 h of CDT (15.4 mg t-PA); no additional intra-procedural fatalities occurred.ConclusionIncreased total t-PA dose and CDT duration were associated with greater PAP reduction without increased bleeding events.

Utilization and outcomes with low dose tissue plasminogen activator as intravenous thrombolytic therapy for ischemic 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..

Rethinking the Doses of Tissue Plasminogen Activator and Deoxyribonuclease Administrated Concurrently for Intrapleural Therapy for Complicated Pleural Effusion and Empyema.

BackgroundComplicated parapneumonic effusions empyema (CPEE) is fairly common and associated with increased morbidity and mortality. The Multicenter Intrapleural Sepsis Trial 2 (MIST 2) established the combination of intrapleural deoxyribonuclease (DNase) and tissue plasminogen activator (tPA) as an effective treatment for CPEE, thereby avoiding surgery and decreasing the length of hospitalization. MIST 2, however, used a labor-intensive protocol with some risk of bleeding. We hypothesize the simpler regimen of concurrent administration of intrapleural tPA and DNase (lower dose of tPA and a higher DNAse dose) to be equally effective with a decreased risk of bleeding.MethodsRetrospective analysis of the concurrent administration of intrapleural tPA and DNase for CPEE during November 2014 to February 2016 was done at a tertiary care center. The inclusion criteria included 1) pleural fluid with any of the following: (a) exudative and loculated effusion in a patient with pneumonia, (b) gram stain/culture positive, (c) macroscopically purulent 2) chest tube placement during current hospitalization 3) concurrent administration of intrapleural tPA and DNase (4mg and 10mg per instillation respectively). The exclusion criteria was 1) chest tube placement prior to current hospitalization and 2) age < eighteen.ResultsSeventeen patients received concurrent tPA and DNase therapy for CPEE in the study period. Two had chest tubes placed prior to current hospitalization and were excluded. Twelve patients (80%) were successfully discharged with clinical resolution of CPEE with medical therapy. One (7%) patient required surgery. No mortality due to pleural sepsis was noted. The median number of concurrent tPA and DNase treatment was two. Median cumulative tPA dose was 8 mg (mean: 14.1±17 mg) and median cumulative DNase dose was 20mg (mean: 19.7 ± 12.2 mg). The median dwell time for the chest tubes was 8.5 days. Our regimen had similar success when compared to MIST 2 and allowed for lesser treatments and cumulative doses. No complication of intrapleural therapy with hemorrhagic conversion of CPEE, or worsening pain leading to discontinuation of therapy was noted.ConclusionThe concurrent administration of intrapleural therapy at lower doses than the current standard MIST 2 protocol is practical, efficient and effective. We suggest a higher DNase dose with a lower tPA dose which may further decrease hemorrhagic complications. Further randomized trials are required to establish the optimal dose of intrapleural therapy for CPEE.

Comparison of Ultrasound-Accelerated versus Pigtail Catheter–Directed Thrombolysis for the Treatment of Acute Massive and Submassive Pulmonary Embolism

PurposeTo compare the technical and clinical effectiveness of ultrasound-accelerated endovascular thrombolysis (USAT) versus pigtail catheter–directed thrombolysis (PCDT) for the treatment of acute pulmonary embolism (PE). Materials and MethodsA single-center retrospective study of patients treated with USAT or PCDT for acute massive or submassive PE between January 2010 and December 2016 was performed by reviewing electronic medical records. Sixty treatments were reviewed (mean patient age, 56.7 y ± 14.6), including 52 cases of submassive PE (21 treated with USAT, 31 with PCDT) and 8 cases of massive PE (3 treated with USAT, 5 with PCDT). Endpoints included pulmonary artery pressure (PAP), Miller PE severity index, tissue plasminogen activator (TPA) dose, infusion duration, procedural variables, and complications. ResultsDemographics, PE severity, and right:left ventricular diameter ratios were similar between groups. USAT and PCDT significantly reduced mean PAP (reductions of 7.4 mm Hg [P = .002] and 8.2 mm Hg [P < .001], respectively) and Miller index scores (reductions of 45.8% [P < .001] and 53% [P < .001], respectively) with similar effectiveness (P = .47 and P = .15, respectively). Procedure (P < .001) and fluoroscopy (P = .001) times were significantly longer in the USAT group. The USAT group underwent fewer sessions (2.2 ± 0.6 vs 2.4 ± 0.6; P = .17) with shorter infusion times (23.9 h ± 8.8 vs 30.4 h ± 12.6; P = .065) and a lower total dose of TPA (27.1 mg ± 11.3 vs 30.4 mg ± 12.6; P = .075) compared with the PCDT group, but the differences were not significant. Complications (P = .07) and 30-day mortality rates (P = .56) were not significantly different between groups. ConclusionsUSAT and PCDT demonstrated comparable effectiveness and safety in the treatment of patients with acute PE.

Abstract WP380: Simulation Based Acute Stroke Responders Training Improves Door-to-Thrombolytic Time

Background: The evaluation of acute ischemic stroke (AIS) patients should be performed expeditiously. Our stroke program maintained our Target: Stroke Honor Roll status in 2014, however, door-to-needle (DTN) time in Quarter 1 and 2 of 2015 showed no significant improvement and did not achieve DTN under 60 minutes in 75% of patients nor under 45 minutes in 50% of patients, despite in-servicing Emergency Department (ED)’s staff on program goals and order sets. The purpose of this project was to more effectively educate emergency stroke responders on clinical recognition and implementation of the organization’s stroke protocol order sets. Simulation as an experiential learning technique, promoting, applied thinking, delegation, and leadership skills. Evidence suggests simulation based training for adult learners promote their engagement and immediate application of learned material. Methods: Simulation: Stroke code responders, including 5 nurses per session, participated in the 90 minute scenario. Stroke protocol order sets were reviewed prior to the simulation of a right hemispheric syndrome. Participants elicited a focused history, National Institutes of Health Stroke Scale, relayed the findings to the neurologist, evaluate exclusion and inclusion criteria, and administered weight-based doses of tissue plasminogen activator (tPA). After a debrief, the participants repeated the simulation to reinforce new knowledge and skills. Descriptive statistics were used to compare mean DTN time before and after simulation training. Results: 153 ED nurses, 8 ED physicians, 6 neurologists, 4 pharmacists, 6 radiology technicians, and 10 phlebotomists participated. Pre -training Q1-Q2 2015 median DTN was 55 minutes, 65% &lt;/= 60 minutes, and 31% &lt;/= 45 minutes. Post-training data from Q1 2016 median DTN was 46 minutes, 75% &lt;/= 60 minutes, and 50% &lt;/= 45 minutes. Conclusion: Simulation based stroke responders training helped to decrease DTN time.

Mixing It Up: Coadministration of tPA/DNase in Complicated Parapneumonic Pleural Effusions and Empyema.

A recent randomized controlled trial showed 12 serial doses of tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) is safe and effective in managing complicated parapneumonic pleural effusions and empyema (CPEE). However, this regimen is laborious, requiring trained personnel to open/close the chest tube 8 times daily for 3 days. We present our observational data using a simplified regimen of coadministered tPA/DNase. This is a retrospective observational study of patients who received coadministered tPA/DNase for CPEE from January 2012 to April 2015 at the University of Texas Medical Branch. Patient demographics, pleural fluid, radiologic and treatment characteristics, and outcomes were collected. Data are presented as proportions and percentages. Our primary outcome was successful treatment without need of surgery and discharge home alive. Secondary outcomes were dose and length of treatment and hospital stay, treatment complications, and 90-day mortality. The study included 39 patients. All pleural effusions were loculated, 59% macroscopically purulent, 50% had a positive organism in Gram stain, and 40% were culture positive. A median of 6 (interquartile range, 3.5 to 6) doses were coadministered mainly via small bore chest tube (≤14 Fr in 79%) with a median of 14.5 (interquartile range, 9.5 to 21.5) hospital days. Overall, 85% were successfully treated without need for surgery. Treatment failures occurred in 15%: 3/39 (7%) received surgery; 3/39 (7%) died. Only 1 (2.5%) complication of hemorrhagic pleural effusion resolved after discontinuation of intrapleural treatment. Our study shows intrapleural coadministration of tPA/DNase was effective and safe in management of CPEE.

Type IV Popliteal Arterial Entrapment Associated With an Osteochondroma

A 27-year-old man complaining of a several-month history of right lower extremity coolness was seen by his primary care physician. He works as a farmer and tends his fields on the farm and commonly squats for milking cows. Ten days before presentation, he developed pain in his right foot with walking along with progressively increased coolness in his right leg. On physical examination, he was found to have a cool right lower extremity and no palpable dorsalis pedis or posterior tibial arterial pulses. Doppler examination produced a faint monophasic posterior tibial signal. No sensory deficits were noted. Computed tomography showed occlusion of the anterior tibial artery along with occlusion of the peroneal and posterior tibial arteries. Increased velocities were noted on the duplex ultrasound examination with provocative maneuvers in the tibial vessels. The patient underwent angiography, which demonstrated the occlusion of the anterior tibial, posterior tibial, and peroneal arteries. Catheters were then delivered to the anterior tibial and posterior tibial to allow infusion of tissue plasminogen activator. With repeated angiography, the posterior tibial artery remained occluded, and the anterior tibial artery opened with flow into the dorsalis pedis. The posterior tibial artery remaining occluded in spite of increased dose of tissue plasminogen activator. Further imaging was performed to look for a potential cause of thrombosis. The patient underwent magnetic resonance angiography with active dorsiflexion and plantar flexion to evaluate for potential popliteal entrapment as the patient’s pulse would diminish with plantar flexion. Magnetic resonance angiography demonstrated a pedunculated osteochondroma arising from the right proximal medial tibia. This lesion had significant mass effect on the adjacent medial gastrocnemius and popliteus muscles. With the active maneuvers performed, there was no evidence of compression; however, with the patient’s history, it was suspected that certain activities would cause compartment compression secondary to the osteochondroma. With this pedunculated osteochondroma, the patient was referred to orthopedics for resection. The patient underwent operative exploration with resection of the osteochondroma and release of his popliteus muscle to open the popliteal compartment. Postoperative duplex ultrasound examination demonstrated return of normal ankle-brachial index.

Is Low-Dose Thrombolysis for Acute Ischemic Stroke a Viable Option?

Epidemiologic studies have shown that Asians have an increased risk for hemorrhagic stroke compared with white patients. This pattern has led to concerns about the safety of full-dose IV tissue plasminogen activator (TPA) in Asian patients with acute ischemic stroke. In Japan, a reduced dose of TPA (0.6 mg/kg) has been approved instead of the conventional dose (0.9 mg/kg). The current study was a randomized trial of these two doses of TPA in …

Utilization of modified diagnostic ultrasound and microbubbles to reduce myocardial infarct size

ObjectiveWe sought to determine whether guided high mechanical index (MI) impulses from a diagnostic ultrasound transducer during an intravenous microbubble infusion could augment low-dose fibrinolytic therapy in treating acute myocardial...

Pharmacokinetics and Pharmacodynamics of Tissue Plasminogen Activator Administered Through an External Ventricular Drain.

Intraventricular hemorrhage (IVH) frequently complicates spontaneous intracerebral or subarachnoid hemorrhage (SAH). Administration of intraventricular tissue plasminogen activator (TPA) accelerates blood clearance, but optimal dosing has not been clarified. Using a standardized TPA dose, we assessed peak cerebrospinal fluid (CSF) TPA concentrations, the rate at which TPA clears, and the relationship between TPA concentration and biological activity. Twelve patients with aneurysmal SAH and IVH, treated with endovascular coiling and ventricular drainage, were randomized to receive either 2mg intraventricular TPA or placebo every 12h (five doses). CT scans were performed 12, 48, and 72h after initial administration, and blood was quantified using the SAH Sum and IVH Scores. CSF TPA and fibrin degradation product (D-dimer) concentrations were measured at baseline and 1, 6, and 12h after the first dose using ELISA assays. Median CSF TPA concentrations in seven TPA-treated patients were 525 (IQR 352-2129), 323 (233-413), and 47 (29-283) ng/ml, respectively, at 1, 6, and 12h after drug administration. Peak concentrations varied markedly (401-8398ng/ml). Two patients still had slightly elevated levels (283-285ng/ml) when the second dose was due after 12h. There was no significant correlation between the magnitude of CSF TPA elevation and the rate of blood clearance or degree of D-dimer elevation. D-dimer peaked at 6h, had declined by 12h, and correlated strongly with radiographic IVH clearance (r=0.82, p=0.02). The pharmacokinetics of intraventricular TPA administration varies between individual patients. TPA dose does not need to exceed 2mg. The optimal administration interval is every 8-12h.

Successful use of recombinant tissue plasminogen activator (r-TPA) for management of chylothorax associated with central venous thrombosis after neonatal cardiac surgery

Postoperative chylothorax is a frequently encountered pathology occurring in up to 5% of patients undergoing surgery for repair of congenital heart disease. Neck vein thrombosis can be associated with chylothorax and may contribute to its severity and duration. Furthermore, neck vessel thrombosis resulting in permanent vessel occlusion may hinder future management, diagnostic studies and cardio-surgical interventions. In this report we are describing a neonate who developed chylothorax on the 7th post-operative day following open-heart surgery. The chylothorax was linked to venous thrombosis in the cannulated right internal jugular vein with thrombus extending to the right atrium. After using low dose tissue plasminogen activator (r-TPA) infusion, the thrombi disappeared and the chylothorax resolved with no complications.

Abstract W MP96: Low Dose Tissue Plasminogen Activator Amplifies Vascular Injury and Worsens Functional Outcomes in Acute Hyperglycemic Stroke Independent of the Model of Reperfusion

Clinically, hyperglycemia (HG) exacerbates reperfusion injury and aggravates tPA-induced hemorrhagic transformation (HT). Yet, most of the experimental hyperglycemic stroke studies exclusively employed suture occlusion model. Only few studies involved tPA in hyperglycemic setting and employed a 10-fold higher dose of tPA than that is used in patients. Thus, in this translational study using suture and thromboembolic occlusion of middle cerebral artery (MCA), with and without human tPA dose, we tested the hypothesis that even acute mild HG worsens the neurovascular injury and functional outcomes irrespective of the method of reperfusion, and that the use of low dose tPA amplifies this injury. Methods: Control and mildly HG rats (140-200 mg/dl, achieved by 30% glucose ip injection 15 min prior to surgery, n=7-9/group) were subjected to MCA occlusion by either suture (90 min) or humanized clot and 24 h reperfusion. tPA (1mg/kg) was injected IV 2 h after induction of ischemia. At 24 h, neurological deficit, infarct size, edema, HT occurrence rate (HT index) and tissue hemoglobin (Hb) were measured. Results: Cerebral blood flow monitoring indicated that % drop at occlusion were similar across the groups and that low dose tPA effectively resolved the clot in the embolic model. tPA did not increase the infarct size in either control or hyperglycemic animals when compared to no tPA groups (Table). HG increased vascular injury (HT index and Hb content) in both suture and embolic occlusion models. The combination of HG and tPA exacerbated the vascular injury and worsened functional outcomes more than each alone. Conclusion: The interaction between HG and even low dose tPA has a significant deleterious effect on cerebrovasculature and functional outcomes independent of the method of reperfusion.

The use of tissue plasminogen activator as continuous infusion into an arteriovenous hemodialysis access in the hemodialysis unit: a case series.

BackgroundThrombolytics such as tissue plasminogen activator are often used by interventional radiologists in the radiology suite to salvage thrombosed hemodialysis arteriovenous fistulae. Thrombolytics are also commonly used in dialysis facilities as a dialysis catheter lock solution or as an infusion into a dialysis catheter when dysfunctional. However, the use of tissue plasminogen activator as a continuous infusion into an arteriovenous fistula in the dialysis facility to treat clot burden is not commonly done.ObjectiveThe aim of our case series is to demonstrate the successful use of tissue plasminogen activator to decrease clot burden in an arteriovenous fistula in the dialysis unit.DesignObservational case series.SettingAn outpatient dialysis facility in a tertiary care hospital.PatientsThree non- consecutive patients were diagnosed with an acute thrombosed arteriovenous fistula either on physical exam or by imaging.MeasurementsA thrombosed fistula as well as successful resolution of clot was illustrated by either physical exam, fistulogram or ultrasound. A functioning fistula demonstrated successful continuation of dialysis and adequate access flow measurements in follow up.MethodThis is a case series that describes the technique of using an infusion of tissue plasminogen activator into an arteriovenous fistula on the dialysis unit by vascular access nurses to treat or diminish clot burden.ResultsWe have described three separate cases where treatments with tissue plasminogen activator infusions on the dialysis unit resulted in objective evidence of decrease in clot burden on ultrasound or fistulogram.LimitationsThe small numbers of our case series requires that the results need to be verified in a larger study. Inclusion and exclusion criteria need to be defined before widespread application of this technique.ConclusionsTo our knowledge this small case series is the first to describe the procedure whereby low dose tissue plasminogen activator is directly infused into the fistula by the vascular access nurse in the dialysis unit during dialysis and not in the interventional suite. This provides additional information to the existing literature that there is an alternative option for dialysis units to diminish clot burden until a more permanent solution is established through angioplasty.

Treatment Outcomes in Pediatric Patients with Pulmonary Embolism Using Low Dose Tissue Plasminogen Activator Therapy

▪Introduction:Pulmonary Embolism (PE) is relatively rare in children but is associated with significant morbidity and many acute and chronic complications. Currently, based on ACCP guidelines, unfractionated heparin or low-molecular-weight heparin (LMWH) remains standard therapy for children with PE and systemic thrombolysis is reserved for life threatening thrombosis due to concerns with bleeding. Thrombolytic therapy has been shown to be more efficacious than anticoagulation alone in adults with PE but similar data in pediatric population is lacking. Specific guidelines for use of tissue plasminogen activator (TPA) in children with PE were created at Children’s Hospital of New Orleans (CHNOLA) in 2008. We have used low dose systemic TPA (0.03 mg/kg/hr initially, increased to 0.05 mg/kg/hr if less than optimal response is seen within 24 hrs) together with unfractionated heparin (5 units/kg/hr) to achieve a goal PTT of 40-60 seconds. Thrombolytic therapy is continued until clot resolution is achieved, but not for a period longer than 72 hrs, at which point patients are transitioned to LMWH.The aim of our study was to determine the effectiveness of systemic low dose TPA therapy in treatment of PE in the pediatric population and also to determine if there are increased bleeding complications.Methods:After IRB approval, a retrospective chart review of patient incidences (PI) with PE and treated with systemic TPA at CHNOLA between June 2008 and June 2014 was performed. Underlying risk factors for thrombophilia were noted. Responses were classified as complete resolution of thrombus (CR), improvement but no complete resolution (PR) or no change in thrombus (NR) based on imaging at the end of TPA treatment. Data were analyzed to determine the efficacy of low dose TPA in treatment of PE.Results:During the specified time, 16 PI were identified for which low dose systemic TPA therapy was used in children with PE. Median age was 13 years. Mean duration of TPA treatment was 51 hrs (range 17-72 hrs). All patients received simultaneous therapy with unfractionated heparin. Seven PI needed an increase in the dose of TPA infusion to 0.05 mg/kg/hr after 24 hrs due to partial or no response to therapy.Nine (56%) PI had complete response, six (38%) were partial responders and one (6%) was classified as a non-responder. All PI were switched to LMWH at the end of systemic TPA. Duration of therapy with TPA did not affect response to treatment (p = 0.16) . There were no major bleeding problems. Furthermore, there were no complications that required TPA to be stopped. Table shows all the 16 PI, risk factors, duration/response to treatment and complications.TableAge (Year)Risk FactorDuration of TPA (Hours)ResponseComplication12 YMTHFR heterozygous + high Homocystein level72PRFecal occult blood positive21 YHip surgery 1 month prior24CRNo19 YLeukemia, Bone marrow transplant 3 weeks prior, central line24CRLeft hand/forearm hematoma6 daysPrematurity, maternal cocaine use72NRNo16 YUnknown48CRNo14 YH/o Deep vein thrombosis72CRNo9 YLeukemia, Downs syndrome72PRNo29 YHistory of Fontan procedure24PRNo13 YDowns Syndrome, hypothyroidism48CRNo11 YDiabetes mellitus72PRNo11YRight hip fracture72CROozing from IV sites16 YOral contraceptive pills48CROozing from IV sites17 YOral contraceptive pills72CRNo9 YDiabetes mellitus, high lipoprotein a72PREpistaxis11 YRight femur surgery17CRNo11 YDiabetes mellitus, high lipoprotein a72PREpistaxisConclusions:To our knowledge, this is the first clinical study of low dose TPA use for PE in pediatric patients. Our results show that low dose TPA therapy is effective and relatively safe in treatment of PE in children. Further large-scale prospective trials are needed to validate the results of our study. DisclosuresNo relevant conflicts of interest to declare.

Thrombolytic therapy using a low dose of tissue plasminogen activator in children

Thrombolytic therapy using a low dose of tissue plasminogen activator in children

Diagnostic Ultrasound Induced Inertial Cavitation to Non-Invasively Restore Coronary and Microvascular Flow in Acute Myocardial Infarction

Ultrasound induced cavitation has been explored as a method of dissolving intravascular and microvascular thrombi in acute myocardial infarction. The purpose of this study was to determine the type of cavitation required for success, and whether longer pulse duration therapeutic impulses (sustaining the duration of cavitation) could restore both microvascular and epicardial flow with this technique. Accordingly, in 36 hyperlipidemic atherosclerotic pigs, thrombotic occlusions were induced in the mid-left anterior descending artery. Pigs were then randomized to either a) ½ dose tissue plasminogen activator (0.5 mg/kg) alone; or same dose plasminogen activator and an intravenous microbubble infusion with either b) guided high mechanical index short pulse (2.0 MI; 5 usec) therapeutic ultrasound impulses; or c) guided 1.0 mechanical index long pulse (20 usec) impulses. Passive cavitation detectors indicated the high mechanical index impulses (both long and short pulse duration) induced inertial cavitation within the microvasculature. Epicardial recanalization rates following randomized treatments were highest in pigs treated with the long pulse duration therapeutic impulses (83% versus 59% for short pulse, and 49% for tissue plasminogen activator alone; p<0.05). Even without epicardial recanalization, however, early microvascular recovery occurred with both short and long pulse therapeutic impulses (p<0.005 compared to tissue plasminogen activator alone), and wall thickening improved within the risk area only in pigs treated with ultrasound and microbubbles. We conclude that although short pulse duration guided therapeutic impulses from a diagnostic transducer transiently improve microvascular flow, long pulse duration therapeutic impulses produce sustained epicardial and microvascular re-flow in acute myocardial infarction.

Low dose tissue plasminogen activator treatment for vascular thrombosis following cardiac catheterization in children: A single center experience

To assess the efficacy and safety of low dose tissue plasminogen activator (tPA) therapy in children with vascular thrombosis following cardiac catheterization. Currently, heparin is the standard of care for vascular thrombosis, however, it may not be efficacious in dissolving existing thrombi. Although tPA is an accepted thrombolytic therapy for life-threatening thrombosis in children, it is not a well-established treatment for the thrombosis of femoral vessels following cardiac catheterization. A retrospective analysis was performed from 1/1/2009 until 6/30/2011 at Rady Children's Hospital-San Diego (RCHSD) reviewing all cases with venous or arterial thrombosis at the vascular access site following cardiac catheterization, and a survey was conducted among the Congenital Cardiovascular Interventional Study Consortium members regarding their experience in tPA therapy. At RCHSD, out of 1,155 catheterizations, 12 children developed femoral thrombosis. In three children, where 12-h heparin therapy was unsuccessful in resolving thrombosis, we used low-dose tPA according to the following regime: 0.05 mg/kg/h for 30 min, followed by 0.1 mg/kg/h for 4 h. We achieved thrombolysis in all cases evidenced by repeat ultrasound and return of palpable pulse with normal limb circulation. No complications were encountered. The survey confirmed that adult tPA dose (0.1-0.5 mg/kg/h) has 100% efficacy in resolving thrombi in children with vascular thrombosis, however, the rate of serious complications was not negligible (15%). tPA is an efficacious therapy to dissolve thrombi that developed as a complication of cardiac catheterization in children. The rate of complications due to tPA may be reduced using a lower dose: 0.05-0.1 mg/kg/h.

Abstract No. 344 - Thrombolytic reperfusion of acute phlegmasia cerulea dolens in congenitally absent IVC

Purpose Absent inferior vena cava(AIVC) is a rare anomaly of the venous system, occurring in 0.15% of general population, and occurs in 5% of patients presenting with unprovoked deep venous thrombosis (DVT) (1,2). AIVC may present as idiopathic phlegmasia cerulea dolens (PCD). Thrombolysis can successfully reduce massive clot burden. Materials and Methods Three patients were reviewed who presented with acute idiopathic PCD and underwent thrombolytic therapy. All were male, age range 25-42 years, with no comorbidities. CT and venograms demonstrated complete absence of the IVC and thrombosed pelvic collateral veins. Thrombolytic therapy consisted of initial 10 mg tissue plasminogen activator (TPA), followed by 1 mg/hr infusion over three to five days with low dose heparin infusion at 300 U/hr. Results All three patients showed initial flow around the dilated iliac vein thrombus, which progressively improved. Thigh diameters decreased by 0.5-1.0 cm per day. Venous stasis color improved by day 2 or 3, with decreasing pain. Follow-up venography showed re-established flow in the ascending paralumbar venous plexus, a collateral pathway for venous drainage. Conclusion 1. PCD in the setting of AIVC has massive clot load in chronically dilated pelvic veins (3). 2. Acute presenting PCD is caused by thrombosis of the pelvic and ascending lumbar veins. 3. Thrombolytic treatment endpoint is the re-establishment of ascending collateral flow. 4. Low dose TPA infusion may reduce the risk of massive reperfusion injury (4).