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

2019 ◽  
Vol 119 (07) ◽  
pp. 1094-1101 ◽  
Author(s):  
Rolf P. Engelberger ◽  
Verena Schroeder ◽  
Michael Nagler ◽  
Raja Prince ◽  
Daniel Périard ◽  
...  

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.

Vascular ◽  
2021 ◽  
pp. 170853812110105
Author(s):  
Mehrdad Farrokhi ◽  
Maria Khurshid ◽  
Sassan Mohammadi ◽  
Bardia Yarmohammadi ◽  
Yaser Bahramvand ◽  
...  

Background Recent in vitro and clinical studies have shown that ultrasound-accelerated catheter-directed thrombolysis (USACDT) can accelerate thrombolysis. Therefore, in this meta-analysis, we aimed to compare the efficacy and safety of USACDT with conventional catheter-directed thrombolysis in patients with deep vein thrombosis. Methods A systematic search of the following electronic databases was performed from their dates of inception to 20 June 2020: MEDLINE, Scopus, Google Scholar, CINAHL, Cochrane Library, and EMBASE. All randomized controlled trials that directly compared the complications and efficacy of USACDT and conventional catheter-directed thrombolysis in patients with deep vein thrombosis were identified. The statistical analysis was performed using comprehensive meta-analysis software. Results Finally, 18 studies with a total of 597 participants were included in our meta-analysis according to the eligibility criteria. Pooled proportion of USACDT success in patients with deep vein thrombosis was 87.8% (18 studies; 95% CI: 83.1–91.3). Success rate was significantly higher in USACDT treatment than in conventional catheter-directed thrombolysis treatment (seven studies; OR: 2.96; 95% CI: 1.69–5.16; P < 0.01)). Although the mean infusion time was higher in catheter-directed thrombolysis treatment compared to USACDT treatment, this difference was not statistically significant (three studies; MD: –1.46; 95% CI: –3.25–0.32; P = 0.10). Moreover, pooled rate of complications was lower in USACDT than catheter-directed thrombolysis which was not statistically significant (seven studies; OR: 0.49; 95% CI: 0.13–1.76; P = 0.27). Conclusion This meta-analysis revealed that USACDT significantly increased the success rate of thrombolysis compared to conventional catheter-directed thrombolysis. Furthermore, USACDT was associated with lower rate of complication and infusion time. Taken together, these findings confirm the superiority of this novel intervention over conventional catheter-directed thrombolysis in treatment of patients with deep vein thrombosis.


2014 ◽  
Vol 111 (06) ◽  
pp. 1153-1160 ◽  
Author(s):  
Rolf P. Engelberger ◽  
Jennifer Fahrni ◽  
Torsten Willenberg ◽  
Frederic Baumann ◽  
David Spirk ◽  
...  

SummaryPatients with ilio-femoral deep-vein thrombosis (DVT) are at high risk of developing the postthrombotic syndrome (PTS). In comparison to anticoagulation therapy alone, extended venography-guided catheter-directed thrombolysis without routine stenting of venous stenosis in patients with ilio-femoral DVT is associated with an increased risk of bleeding and a moderate reduction of PTS. We performed a prospective single-centre study to investigate safety, patency and incidence of PTS in patients with acute iliofemoral DVT treated with fixed-dose ultrasound-assisted catheter-directed thrombolysis (USAT; 20 mg rt-PA during 15 hours) followed by routing stenting of venous stenosis, defined as residual luminal narrowing >50%, absent antegrade flow, or presence of collateral flow at the site of suspected stenosis. A total of 87 patients (age 46 ± 21 years, 60% women) were included. At 15 hours, thrombolysis success ≥50% was achieved in 67 (77%) patients. Venous stenting (mean 1.9 ± 1.3 stents) was performed in 70 (80%) patients, with the common iliac vein as the most frequent stenting site (83%). One major (1%; 95% CI, 0–6%) and 6 minor bleedings (7%; 95%CI, 3–14%) occurred. Primary and secondary patency rates at 1 year were 87% (95% CI, 74–94%) and 96% (95% CI, 88–99%), respectively. At three months, 88% (95% CI, 78–94%) of patients were free from PTS according to the Villalta scale, with a similar rate at one year (94%, 95% CI, 81–99%). In conclusion, a fixed-dose USAT regimen followed by routine stenting of underlying venous stenosis in patients with iliofemoral DVT was associated with a low bleeding rate, high patency rates, and a low incidence of PTS.


1998 ◽  
Vol 79 (03) ◽  
pp. 517-519 ◽  
Author(s):  
Stephane Heymans ◽  
Raymond Verhaeghe ◽  
Luc Stockx ◽  
Désiré Collen

SummaryThe feasibility of catheter-directed thrombolysis with recombinant staphylokinase was evaluated in six selected patients with deep vein thrombosis. The patients underwent intrathrombus infusion of recombinant staphylokinase (2 mg bolus followed by a continuous infusion of 1 mg/h). Heparin was given via the catheter as a bolus (5000 U) and as a continuous infusion (1000 U/h). Complete lyis was obtained in five patients and partial lysis in one patient. Complications consisted of minor bleeding in four subjects. Symptomatic reocclusion occurred in one. Debulking of the thrombus mass by a high speed rotating impeller (n = 1) and stenting (n = 3) were used as additional interventions. An underlying anatomical abnormality was present in two patients. Long term follow up revealed normal patency in all patients and normal valve function in four patients. Symptomatic venous insufficiency with valve dysfunction was present in the two with a second thrombotic episode.Thus catheter-directed infusion of recombinant staphylokinase in patients with deep vein thrombosis appears feasible and may be associated with a high frequency of thrombolysis. Larger studies to define the clinical benefit of this treatment appear to be warranted.


1991 ◽  
Vol 65 (01) ◽  
pp. 028-032 ◽  
Author(s):  
B Boneu ◽  
G Bes ◽  
H Pelzer ◽  
P Sié ◽  
H Boccalon

SummaryThis study was performed to determine the accuracy of D-Dimer fibrin derivatives, thrombin-antithrombin III (TAT) complexes and prothrombin fragments 1 + 2 (F 1 + 2) determinations for the diagnosis of deep vein thrombosis (DVT). One hundred and sixteen consecutive patients referred to the angiology unit of our hospital for a clinically suspected DVT were investigated. They were submitted to mercury strain gauge plethysmography and to ultrasonic duplex scanning examination; in cases of inconclusive results or of proximal DVT (n = 35), an ascending phlebography was performed. After these investigations were completed, the diagnosis of DVT was confirmed in 34 and excluded in 82. One half of the patients were already under anticoagulant therapy at the time of investigation. The 3 biological markers were assayed using commercially available ELISA techniques and the D-Dimer was also assayed with a fast latex method. The normal distribution of these markers was established in 40 healthy blood donors. The most accurate assay for the diagnosis of DVT was the D-Dimer ELISA which had both a high sensitivity (94%) and a high negative predictive value (95%). The D-Dirner latex, TAT complexes and F 1 + 2 were far less sensitive and provided negative predictive values which ranged between 78 and 85%. In spite of positive and significant correlations between the levels of ihe 3 markers, their association did not improve their overall accuracy for detecting D\/L Therefore, with the exception of the D-Dimer ELISA, these markers were of little value for the diagnosis of DVT in this specific population.


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