(More than) doubling down: Effective fibrinolysis at a reduced rt-PA dose for catheter-directed thrombolysis combined with histotripsy

Deep vein thrombosis is a major source of morbidity and mortality worldwide. For acute proximal deep vein thrombosis, catheter-directed thrombolytic therapy is an accepted method for vessel recanalization. Thrombolytic therapy is not without risk, including the potential for hemorrhagic bleeding that increases with lytic dose. Histotripsy is a focused ultrasound therapy that generates bubble clouds spontaneously in tissue at depth. The mechanical activity of histotripsy increases the efficacy of thrombolytic therapy at doses consistent with current pharmacomechanical treatments for venous thrombosis. The objective of this study was to determine the influence of lytic dose on histotripsy-enhanced fibrinolysis. Human whole blood clots formed in vitro were exposed to histotripsy and a thrombolytic agent (recombinant tissue plasminogen activator, rt-PA) in a venous flow model perfused with plasma. Lytic was administered into the clot via an infusion catheter at concentrations ranging from 0 (control) to 4.54 μg/mL (a common clinical dose for catheter-directed thrombolysis). Following treatment, perfusate samples were assayed for markers of fibrinolysis, hemolysis, and intact red blood cells and platelets. Fibrinolysis was equivalent between the common clinical dose of rt-PA (4.54 μg/mL) and rt-PA at a reduction to one-twentieth of the common clinical dose (0.23 μg/mL) when combined with histotripsy. Minimal changes were observed in hemolysis for treatment arms with or without histotripsy, potentially due to clot damage from insertion of the infusion catheter. Likewise, histotripsy did not increase the concentration of red blood cells or platelets in the perfusate following treatment compared to rt-PA alone. At the highest lytic dose, a refined histotripsy exposure scheme was implemented to cover larger areas of the clot. The updated exposure scheme improved clot mass loss and fibrinolysis relative to administration of lytic alone. Overall, the data collected in this study indicate the rt-PA dose can be reduced by more than a factor of ten and still promote fibrinolysis when combined with histotripsy.

Quality of life after ischaemic stroke—accent on patients with thrombolytic therapy

Background Intravenous thrombolysis is a widely approved treatment method for acute ischemic stroke (AIS). Nevertheless, there is a growing interest in its impact on functional outcomes and Health-related Quality of life (HR-QoL). We aimed to evaluate and compare the HR-QoL in patients receiving intravenous thrombolysis (IVT) and in those without thrombolytic therapy during the first 3-month post-stroke in a defined Bulgarian population. Results Patients treated with IVT have simillar functional outcomes and HR-QoL on the third month as the group with conservative treatment, besides their higher NIHSS on admission. Patients with IVT had better self-assessed recovery after the AIS. The higher NIHSS and mRS scores and the lower HR-QoL on discharge are reliable predictors for a poor functional outcome on the third month. A door-to-needle of 60 min or less, and the absence of pathological neuroimaging findings 24-h post IVT predict more beneficial HR-QoL outcome. Conclusion There were no significant differences in HR-QoL and functional outcomes between the groups. Nevertheless, IVT is a treatment option with great importance for improving the clinical outcomes after ischemic stroke, which should be performed in well selected patients.

Thrombus-Targeting Polymeric Nanocarriers and Their Biomedical Applications in Thrombolytic Therapy

Due to the high morbidity and mortality of cardiovascular diseases, there is an urgent need for research on antithrombotic strategies. In view of the short half-life, insufficient drug penetration, poor targeting capabilities, and hemorrhagic side-effects of traditional thrombus treatment methods, the combination of thrombolytic therapy and nanocarriers brought by the development of nanotechnology in recent years may provide effective solutions for these undesirable side-effects caused by insufficient targeting. Polymeric nanocarriers, based on macromolecules and various functional groups, can connect specific targeting molecules together through chemical modification to achieve the protection and targeted delivery of thrombolytic drugs. However, simple chemical molecular modifications may be easily affected by the physiological environment encountered in the circulatory system. Therefore, the modification of nanocarriers with cell membranes can provide camouflage to these platforms and help to extend their circulation time while also imparting them with the biological functions of cell membranes, thus providing them with precise targeting capabilities, among which the most important is the biological modification of platelet membranes. In addition, some nanoparticles with their own therapeutic functions have also been developed, such as polypyrrole, which can exhibit a photothermal effect to induce thrombolysis. Herein, combined with the mechanism of thrombosis and thrombolysis, we outline the recent advances achieved with thrombus-targeting nanocarriers with regard to thrombosis treatment. On this basis, the design considerations, advantages, and challenges of these thrombolytic therapies in clinical transformation are discussed.

Achieving More Rapid Door-to-Needle Times and Improved Outcomes in Acute Ischemic Stroke in a Nationwide Quality Improvement Intervention

Background and Purpose: The benefits of tPA (tissue-type plasminogen activator) in acute ischemic stroke are time-dependent. However, delivery of thrombolytic therapy rapidly after hospital arrival was initially occurring infrequently in hospitals in the United States, discrepant with national guidelines. Methods: We evaluated door-to-needle (DTN) times and clinical outcomes among patients with acute ischemic stroke receiving tPA before and after initiation of 2 successive nationwide quality improvement initiatives: Target: Stroke Phase I (2010–2013) and Target: Stroke Phase II (2014–2018) from 913 Get With The Guidelines-Stroke hospitals in the United States between April 2003 and September 2018. Results: Among 154 221 patients receiving tPA within 3 hours of stroke symptom onset (median age 72 years, 50.1% female), median DTN times decreased from 78 minutes (interquartile range, 60–98) preintervention, to 66 minutes (51–87) during Phase I, and 50 minutes (37–66) during Phase II ( P <0.001). Proportions of patients with DTN ≤60 minutes increased from 26.4% to 42.7% to 68.6% ( P <0.001). Proportions of patients with DTN ≤45 minutes increased from 10.1% to 17.7% to 41.4% ( P <0.001). By the end of the second intervention, 75.4% and 51.7% patients achieved 60-minute and 45-minute DTN goals. Compared with the preintervention period, hospitals during the second intervention period (2014–2018) achieved higher rates of tPA use (11.7% versus 5.6%; adjusted odds ratio, 2.43 [95% CI, 2.31–2.56]), lower in-hospital mortality (6.0% versus 10.0%; adjusted odds ratio, 0.69 [0.64–0.73]), fewer bleeding complication (3.4% versus 5.5%; adjusted odds ratio, 0.68 [0.62–0.74]), and higher rates of discharge to home (49.6% versus 35.7%; adjusted odds ratio, 1.43 [1.38–1.50]). Similar findings were found in sensitivity analyses of 185 501 patients receiving tPA within 4.5 hours of symptom onset. Conclusions: A nationwide quality improvement program for acute ischemic stroke was associated with substantial improvement in the timeliness of thrombolytic therapy start, increased thrombolytic treatment, and improved clinical outcomes.

Application Effect of Intelligent Monitoring of Emergency Nursing Process Reengineering in the Thrombolytic Therapy of Acute Myocardial Infarction

The application of emergency nursing process in intravenous thrombolytic therapy for patients with acute myocardial infarction was discussed. 100 patients with ST segment elevation myocardial infarction who met the inclusion and exclusion criteria were selected for intravenous thrombolysis. 50 patients with ST segment elevation myocardial infarction were treated from December 2018 to June 2019. The first-aid time and treatment effect of the two groups were compared. The results showed that the first aid time in the optimized process group was less than that in the conventional flow group ( P < 0.05 ); the ECG rate was higher within 10 min than that in the conventional flow group ( P < 0.05 ). It indicates that standardized and meticulous nursing procedures can avoid repetition and omissions and improve work efficiency. The application of the emergency care process in the emergency care of patients with acute myocardial infarction can win more rescue time and then improve the success rate of their rescue.