Low-dose Recombinant Tissue Plasminogen Activator Research Articles

Combined treatment of submacular hemorrhage with low-dose subretinal recombinant tissue plasminogen activator and intravitreal conbercept

BackgroundPars Plana Vitrectomy (PPV) combined with subretinal injection of low-dose recombinant tissue plasminogen activator (rt-PA) and intravitreal injection of Conbercept as a novel therapy for submacular hemorrhage (SMH) requires evaluation.MethodsIn a retrospective interventional clinical study, 14 eyes of 14 patients with SMH underwent PPV along with rt-PA (subretinal) and Conbercept (intravitreal) injections. The main outcomes included best-corrected visual acuities (BCVAs), degrees of blood displacement, and adverse events. All patients completed at least 6-month follow-up visits.ResultsMean BCVAs significantly improved at 7 days (22.29 ± 15.35), 1 month (30.71 ± 16.42), 3 months (38.29 ± 13.72), 4 months (38.86 ± 14.15), and 6 months (41.21 ± 14.91) post-treatment compared to baseline (16.36 ± 13.97) (F = 12.89, P = 0.004). The peak improvement in BCVAs occurred at 6 months postoperatively. The procedure effectively eliminated subfoveal hemorrhages in all eyes, with clots removal and absorption occurring within one month and complete regression by 3-month follow-up visits. Postoperatively, two cases of AMD resulted in discoid scars on the fundus. No instances of rt-PA-related retinal toxicity were observed during the follow-up period.ConclusionThe combined approach of PPV with low-dose rt-PA and anti-VEGF shows promise in enhancing both vision and anatomical structure in SMH therapy. Individualized treatment plans tailored to the primary disease should be developed to optimize visual prognoses.Trial registrationRetrospectively registered No.ChiCTR2100053034. Registration date: 10/11/2021.

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.

Low-Dose Thrombolysis in an Intermediate High-Risk Submassive Pulmonary Embolism With Right Atrial Thrombus: A Case Report

BACKGROUND: Venous thromboembolism, encompassing pulmonary embolism (PE) and deep vein thrombosis (DVT), is the third most common acute cardiovascular syndrome. It requires prompt diagnosis and risk-based treatment strategies. CASE: A 47-year-old male, 30-pack-year smoker who recently underwent open reduction and internal fixation of the right femur presented with dyspnea. There was no hemodynamic instability. Twelve-lead electrocardiogram showed sinus rhythm with incomplete right bundle-branch block, and troponin was elevated. Chest x-ray showed dilated right descending pulmonary artery. Two-dimensional echocardiogram revealed right atrial thrombus with right ventricular dysfunction. Computed tomography of the pulmonary artery confirmed massive PE with infarct on the posterobasal segment of the right lower lobe. Venous duplex scan of the lower extremities showed an acute DVT of the right femoral vein, popliteal vein, and peroneal vein. Anticoagulation was started. With a dilemma of a recent surgery in an intermediate high-risk submassive PE, options other than guideline-recommended systemic thrombolysis were considered. A multidisciplinary consensus recommended the administration of low-dose thrombolysis, which later resulted to clinical improvement. CONCLUSION: This is the first documented local case of successful resolution of a right atrial thrombus with pulmonary thrombus and DVT using low-dose thrombolysis, without complications of bleeding, in a patient with contraindications to thrombolysis. With more clinical experience and studies of low-dose recombinant tissue plasminogen activator in this special population, it can offer a promising treatment option. KEYWORDS: pulmonary embolism, submassive, low-dose systemic thrombolysis, contraindication for thrombolysis, alteplase, tPA, right atrial thrombus

Effect of intraventricularly administered low-dose recombinant tissue plasminogen activator on interleukin 1-beta and transforming growth factor beta concentrations in cerebrospinal fluid of patients with primary intracerebral hemorrhage associated with intraventricular hemorrhage: A retrospective study.

It is increasingly recognized that modulation of brain inflammation may uncover new potential therapeutic strategies for stroke. Recent studies have shifted focus from immunological implications in ischemic stroke to a more devastating form; the hemorrhagic stroke.The aim of this study was to investigate the neuroinflammatory response in cerebrospinal fluid in patients with primary intracerebral hemorrhage (ICH) associated with intraventricular hemorrhage (IVH) in the presence of low-dose recombinant tissue plasminogen activator (rt-PA).This retrospective study included 88 adults with primary ICH associated with IVH. Patients were divided into 2 groups: rt-PA group and non-rt-PA group, which received normal standard of care for this diagnosis. The rt-PA group was treated via catheter-based clot lysis using low-dose rt-PA injected through the external ventricular drain (EVD) system, and the non-rt-PA group was treated with saline applied to EVD system in equivalent volume. Cerebrospinal fluid samples from rt-PA were obtained from the EVD system at 4 time points: once before the drug administration, and then on day 1, 3, and 7. No attempt at randomization was made. The decision to inject rt-PA was based on the preference of the primary attending neurologist and the ability to obtain consent. Temporal interleukin-1 beta and transforming growth factor beta concentration changes were analyzed and compared between the 2 groups.The concentration of interleukin-1 beta was significantly lower in the rt-PA group than in the non-rt-PA group on day 7. In addition, the concentration of transforming growth factor beta was significantly higher in the rt-PA group than in the non-rt-PA group on day 1. There was a significant difference in interleukin-1 beta concentration between days 0 and 1 in comparison to day 3 in the rt-PA group, and between day 0 in comparison to day 3 and 7 in the non-rt-PA group. We also observed a significant difference in transforming growth factor beta concentration between days 0 and 1 and between days 3 and 7.The different pattern of pro- and anti-inflammatory cytokines in patients with ICH associated with IVH suggest distinct characteristics of secondary brain injury depending on the treatment modality.

Effectiveness of Combined External Ventricular Drainage with Intraventricular Fibrinolysis for the Treatment of Intraventricular Haemorrhage with Acute Obstructive Hydrocephalus

Background: Intraventricular haemorrhage (IVH) patients with acute obstructive hydrocephalus (AOH) who require external ventricular drainage (EVD) are at high risk for poor outcomes. Intraventricular fibrinolysis (IVF) with low-dose recombinant tissue plasminogen activator (rtPA) can be used to improve patient outcomes. Here, we evaluated the impact of IVF on the risk of death and the functional outcomes in IVH patients with AOH. Methods: This prospective cohort study included IVH patients with hypertensive intracranial haemorrhage complicated by AOH who required EVD. We evaluated the risk of death and the functional outcomes at 1 and 3 months, with a specific focus on the impact of combined EVD with IVF by low-dose rtPA. Results: Between November 30, 2011 and December 30, 2014, 80 patients were included. Forty-five patients were treated with EVD alone (EVD group) and 35 received IVF (EVD+IVF group). The 30- and 90-day mortality rates were lower in the EVD+IVF group than in the EVD group (42.2 vs. 11.4%, p = 0.003, and 62.2 vs. 20%, p < 0.001, respectively). The Graeb scores were significantly lower in the EVD+IVF group than in the EVD group (p ≤ 0.001) during the first 3 days and on day 7 after assignment. The 30-day good functional outcome (modified Rankin Scale [mRS] score 0–3) was also higher in the EVD+IVF group than in the EVD group (6.7 vs. 28.6%, p = 0.008). However, the 90-day good functional outcome (mRS score 0–3) did not significantly increase in the EVD+IVF group (30.8% in the EVD group vs. 51.6% in the EVD+IVF group, p = 0.112). Conclusions: In our prospective observational study, EVD+IVF was associated with a lower risk of death in IVH patients. EVD+IVF improved the chance of having a good functional outcome at 1 month; however, this result was no longer observed at 3 months.

The Successful Use of Low-Dose Recombinant Tissue Plasminogen Activator for Treatment of Intracardiac/Pulmonary Thrombosis During Liver Transplantation

Intracardiac thrombosis and pulmonary embolism are uncommon complications during liver transplantation but carry a high mortality rate. We report the successful use of low-dose recombinant tissue plasminogen activator (0.5-4 mg) administration in 4 patients. Early diagnosis through transesophageal echocardiography and pulmonary artery catheterization may have contributed to the rapid thrombolysis.

Tissue plasminogen activator infusion as a treatment for hemodialysis catheter dysfunction

AbstractBACKGROUNDThe formation of a fibrin sheath thrombus is the most common cause of hemodialysis catheter dysfunction (HCD). The infusion of a low‐dose recombinant tissue plasminogen activator (rtPA) has been shown to be safe and effective. However, there is no consensus as to the optimum amount of rtPA.OBJECTIVETo evaluate the safety and efficacy of a low‐dose rtPA infusion for the treatment of fibrin sheath thrombus.METHODSWe did a retrospective review of patients with HCD who were treated with rtPA infusion between August 2006 and August 2007. Each patient had a radiographic evaluation to rule out malposition before administering 1 mg rtPA in 50 mL of normal saline over a 1‐hour period per port (total of 2 mg).RESULTSA total of 74 patients had a total of 86 infusions administered. Their mean age was 62 years, and 52% were male. The clinical success rate, defined as an ability to support at least 1 successful dialysis session, was 95.3%. No major procedure‐related complications occurred. The median catheter patency was 40.5 days.CONCLUSIONRtPA, administered at current study dose, safely and effectively restores catheter function. To our knowledge, this is the lowest dose and shortest infusion time that has been studied.

RETINAL VEIN OCCLUSION AND LOW-DOSE FIBRINOLYTIC THERAPY (R.O.L.F.)

To investigate the efficacy of intravenous thrombolysis with low-dose recombinant tissue plasminogen activator (rt-PA) in recent-onset central retinal vein occlusion (CRVO) or branch retinal vein occlusion. This was a prospective, randomized, controlled multicenter trial in patients with CRVO or branch retinal vein occlusion, best-corrected visual acuity < or =20/50, and onset of symptoms within 11 days before treatment. In each group, patients were randomized to either hemodilution or thrombolysis with 50 mg of rt-PA with concomitant intravenous heparinization. The primary clinical outcome measure was improvement in best-corrected visual acuity from baseline at 1 year. Fifty-two subjects were enrolled in the study. Patients with CRVO (n = 41) who were treated with rt-PA exhibited a significant improvement in best-corrected visual acuity compared with those who received hemodilution (P < 0.0001). At 1-year follow-up, the proportion of eyes with CRVO achieving an improvement in visual acuity of three or more lines was 45% after treatment with rt-PA and 21% after hemodilution therapy. The median final best-corrected visual acuity among CRVO patients given rt-PA was 20/60 (light perception, 20/15) compared with 20/400 (light perception, 20/20) in the hemodilution group. There were no significant differences among patients with branch retinal vein occlusion (n = 11). We observed no serious adverse events. No significant differences were found regarding the development of ocular neovascularization. Treatment with intravenous low-dose rt-PA improved visual outcome in CRVO. Thrombolysis was not associated with a lower risk of ocular neovascularization, indicating that the mechanisms involved in this process occur at an early stage.

Rheolytic Thrombectomy for Cerebral Sinus Thrombosis

Cerebral venous and sinus thrombosis (CVST) is an uncommon cause of stroke that is associated with poor outcomes in high-risk patients who present with stupor or coma, rapidly progressive neurologic deficits or progressive neurologic deficits during therapeutic anticoagulation. We report the rapid treatment of CVST in six patients at high risk for poor outcomes (death or dependency) using rheolytic thrombectomy combined with locally administered low-dose recombinant tissue plasminogen activator (rt-PA), and review the literature on rheolytic thrombectomy for CVST. All of the procedures were technically successful. No complications occurred. Two patients experienced partial rethrombosis following rheolytic thrombectomy requiring a second treatment. Preexisting hemorrhagic infarcts in two patients remained stable. Two of six patients experienced excellent clinical outcomes. Two had good outcomes. There were two deaths from irreversible cerebral injury caused by extensive CVST that had occurred prior to the endovascular treatments. In 24 cases of rheolytic thrombectomy for CVST that were reviewed from this series and previously published reports, the large majority of patients experienced good to excellent clinical outcomes. Extensive CVST in high-risk patients can be rapidly fatal. Rheolytic thrombectomy combined with locally administered, low-dose recombinant tissue plasminogen activator (rt-PA) is a safe and effective endovascular method to rapidly recanalize the intracranial dural sinuses in high-risk patients with CVST.

Thrombolysis of Venous and Arterial Thrombosis by Catheter-Directed Low-Dose Infusion of Tissue Plasminogen Activator in Children

Thrombolytic therapy is a well-defined treatment option for arterial and venous thrombosis in adults. In contrast, uniform recommendations regarding the indication, route of administration, and dosing of thrombolytic therapy in children are not available. The authors report the successful resolution of bilateral pulmonary embolism and popliteal artery thrombosis in an 11-year-old girl and 13-year-old girl, respectively, by catheter-directed thrombolysis with low-dose recombinant tissue plasminogen activator. Catheter-directed low-dose thrombolysis is an efficient treatment option for severe venous and arterial thrombosis in children.

Recombinant tissue plasminogen activator infusion for hemodialysis catheter clearance

Hemodialysis (HD) catheter occlusion is a common cause of poor blood flow and inadequate dialysis. In order to address this problem in our pediatric dialysis unit, we elected to use short (2-h) infusions of low-dose recombinant tissue plasminogen activator (rtPA) for thrombolysis of occluded catheters. Catheters meeting diagnostic criteria for thrombosis were infused with 2.5 mg rtPA in 25 ml 0.9 normal saline over 2 h prior to dialysis. Retrospective data collection was carried out to assess the success of this procedure. Variables assessed included blood flow (Qb), transmembrane pressure (TMP) and venous pressure (VP) before and after rtPA infusion. Seven catheter thromboses in six patients were successfully treated with rtPA; there were significant improvements in Qb ( p <0.01), TMP ( p <0.01), and VP ( p <0.02). At 32 weeks after rtPA therapy, Kaplan-Meier survival analysis showed a 60% probability of primary catheter patency. At the end of the study, 85% of catheters had adequate function as defined by a Qb >200 ml/min. No adverse events were observed. Low-dose rtPA infusion is safe and effective for catheter thrombolysis in outpatient pediatric HD patients. It may serve as an alternative method of administration to local instillation and may be used to restore patency before resorting to surgical revisions.

Successful recanalization of late portal vein thrombosis after liver transplantation using systemic low-dose recombinant tissue plasminogen activator

Successful recanalization of late portal vein thrombosis after liver transplantation using systemic low-dose recombinant tissue plasminogen activator

Ultramicrosurgical Removal of Subretinal Hemorrhage in Cats

Subretinal hemorrhages are associated with progressive degeneration of the outer retina and a corresponding poor visual prognosis. Mixed results have been reported in previous attempts to remove such subretinal hemorrhages. We developed an ultramicrosurgical system that used the control of a stereotactic micromanipulator to direct a micropipette tip through a small retinotomy into the subretinal space in three cat eyes. Low-dose recombinant tissue plasminogen activator was then introduced into the subretinal space around the subretinal hemorrhage via a controlled microinfusion system. The recombinant tissue plasminogen activator solution facilitated clot lysis and subsequent removal through the micropipette. Light- and electron-microscopic analysis of histopathologic specimens disclosed good preservation of retinal architecture in the three cat eyes in which experimental subretinal hemorrhages were removed. This was in contrast to the retinal degeneration observed in similar but untreated experimental subretinal hemorrhages.