Efficacy of venous recanalization by non-invasive pulsed ultrasonic cavitation therapy on swine model of acute deep venous thrombosis with 14 days of follow-up

Abstract Background Post thrombotic syndrome is a frequent complication of deep venous thrombosis and is associated with high morbidity and hospitalization. Treatments currently available are invasive, involve use of endovenous procedures with stents and balloons, and frequently require general anesthesia. Pulsed cavitational ultrasound therapy (PCUT) emerged recently as a new technique to destroy remotely soft tissue. We recently demonstrated that PCUT was able to recanalize non-invasively in in vitro model of acute venous thrombosis (human blood clot). Purpose We aim to test the safety and efficacy of venous recanalization by noninvasive PCUT in vivo swine model of acute venous thrombosis. Methods All the experiments were performed on White large X Landrace swine. We induced an acute femoral deep venous thrombosis by using occlusive balloons introduced from jugular and popliteal vein combined with local injection of 50 IU of human thrombin. A 3 cm length occlusive thrombosis was obtained after 2 hours. Swines were divided in three groups: one with PCUT without follow-up (n=11), one with PCUT and follow-up at 14 days (n=8), and a control group also followed for 14 days (n=5). Acutely and during the follow up all swines received curative anticoagulation. To achieve PCUT, a 2.25 MHz transducer centered by a linear probe was used and cavitation was obtained in the center of the vein (Figure). After manual determination of thrombus location, a robotic arm was used to automatically move the transducer along the thrombus. Effectiveness of recanalization was evaluated by echo-Doppler and phlebography. Safety was assessed by Doppler ultrasound of the insonified area (artery, veins and surrounding tissue) and by histological analysis (local femoral vein and artery and lungs for pulmonary embolism). Results Among the 24 swines, we obtained 22 occlusive venous thromboses and 2 partial. The median length of the thrombus was 26±4.4 mm with vein diameter of 8.5±1.6 mm. Acutely, thrombosis recanalization was systematically obtained among the 19 swine with PCUT with median treatment duration of 33 minutes with residual diameter of 2.9±0.9 mm. No extravasation of contrast material or hematoma was observed after the therapy. After a 14-day follow-up, 75% of recanalisation remain permeable vs. 0% of vein permeable in the no therapy group (p=0.008). Residual diameter was 2.6±1.2 mm, which correspond to 50% of the venous diameter. No vein or artery damage and no embolism or pulmonary infarction was observed in all pigs. Figure 1 Conclusion We have demonstrated in vivo the safety and the efficacy of PCUT for non-invasive venous recanalization, persistent after 2 weeks. Acknowledgement/Funding French society of cardiology

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Non‐invasive recanalization of deep venous thrombosis by high frequency ultrasound in a swine model with follow‐up

Journal of Thrombosis and Haemostasis ◽

10.1111/jth.15034 ◽

2020 ◽

Vol 18 (11) ◽

pp. 2889-2898

Author(s):

Guillaume Goudot ◽

Lina Khider ◽

Costantino Del Giudice ◽

Tristan Mirault ◽

Alexandre Galloula ◽

...

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

High Frequency ◽

Swine Model ◽

High Frequency Ultrasound ◽

Non Invasive ◽

Frequency Ultrasound

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Investigations into the Clinical Utility of Latex D-Dimer in the Diagnosis of Deep Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651178 ◽

1993 ◽

Vol 69 (01) ◽

pp. 008-011 ◽

Cited By ~ 22

Author(s):

Cedric J Carter ◽

D Lynn Doyle ◽

Nigel Dawson ◽

Shauna Fowler ◽

Dana V Devine

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Lower Limb ◽

Clinical Utility ◽

Rapid Test ◽

Fibrin Degradation Product ◽

Current Form ◽

Non Invasive ◽

Clinically Significant ◽

D Dimer

SummaryThe serial use of non-invasive tests has been shown to be a safe method of managing outpatients who are suspected of having lower limb deep venous thrombosis (DVT). Objective testing has shown that the majority of these outpatients do not have venous thrombosis. A rapid test to exclude DVT in these patients, without the need for expensive and inconvenient serial non-invasive vascular testing, would have practical and economic advantages.Studies measuring the fibrin degradation product D-dimer using enzyme-linked immunoassays (EIA) in patients with veno-graphically proven DVT suggest that it should be possible to exclude this condition by the use of one of the rapid latex bead D-dimer tests.We have examined 190 patients with suspected DVT using both a latex and an EIA D-dimer assay. The latex D-dimer test used in this study was negative in 7 of the 36 proven cases of DVT. This sensitivity of only 80% is not sufficient to allow this type of assay, in its current form, to be used as an exclusion test for DVT. The same plasma samples were tested with an EIA assay. This information was used to mathematically model the effects of selecting a range of D-dimer discriminant cut off points for the diagnosis of DVT. These results indicate that 62% of suspected clinically significant DVT could have this diagnosis excluded, with a 98% sensitivity, if the rapid latex or equivalent D-dimer test could be reformulated to measure less than 185 ng/ml of D-dimer.

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High incidence of patients lost to follow-up after venous thromboembolism diagnosis – Identifying an unmet need for targeted transition of care

Vascular ◽

10.1177/17085381211020969 ◽

2021 ◽

pp. 170853812110209

Author(s):

Rae S Rokosh ◽

Jack H Grazi ◽

David Ruohoniemi ◽

Eugene Yuriditsky ◽

James Horowitz ◽

...

Keyword(s):

Emergency Department ◽

Pulmonary Embolism ◽

Venous Thromboembolism ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Time Of Day ◽

Transition Of Care ◽

Initial Discharge ◽

Significant Difference

Objectives Venous thromboembolism, including deep venous thrombosis and pulmonary embolism, is a major source of morbidity, mortality, and healthcare utilization. Given the prevalence of venous thromboembolism and its associated mortality, our study sought to identify factors associated with loss to follow-up in venous thromboembolism patients. Methods This is a single-center retrospective study of all consecutive admitted (inpatient) and emergency department patients diagnosed with acute venous thromboembolism via venous duplex examination and/or chest computed tomography from January 2018 to March 2019. Patients with chronic deep venous thrombosis and those diagnosed in the outpatient setting were excluded. Lost to venous thromboembolism-specific follow-up (LTFU) was defined as patients who did not follow up with vascular, cardiology, hematology, oncology, pulmonology, or primary care clinic for venous thromboembolism management at our institution within three months of initial discharge. Patients discharged to hospice or dead within 30 days of initial discharge were excluded from LTFU analysis. Statistical analysis was performed using STATA 16 (College Station, TX: StataCorp LLC) with a p-value of <0.05 set for significance. Results During the study period, 291 isolated deep venous thrombosis, 25 isolated pulmonary embolism, and 54 pulmonary embolism with associated deep venous thrombosis were identified in 370 patients. Of these patients, 129 (35%) were diagnosed in the emergency department and 241 (65%) in the inpatient setting. At discharge, 289 (78%) were on anticoagulation, 66 (18%) were not, and 15 (4%) were deceased. At the conclusion of the study, 120 patients (38%) had been LTFU, 85% of whom were discharged on anticoagulation. There was no statistically significant difference between those LTFU and those with follow-up with respect to age, gender, diagnosis time of day, venous thromboembolism anatomic location, discharge unit location, or anticoagulation choice at discharge. There was a non-significant trend toward longer inpatient length of stay among patients LTFU (16.2 days vs. 12.3 days, p = 0.07), and a significant increase in the proportion of LTFU patients discharged to a facility rather than home ( p = 0.02). On multivariate analysis, we found a 95% increase in the odds of being lost to venous thromboembolism-specific follow-up if discharged to a facility (OR 1.95, CI 1.1–3.6, p = 0.03) as opposed to home. Conclusions Our study demonstrates that over one-third of patients diagnosed with venous thromboembolism at our institution are lost to venous thromboembolism-specific follow-up, particularly those discharged to a facility. Our work suggests that significant improvement could be achieved by establishing a pathway for the targeted transition of care to a venous thromboembolism-specific follow-up clinic.

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Long-term Clinical Follow-up in 265 Patients with Deep Venous Thrombosis Initially Treated with either Unfractionated Heparin or Dalteparin: A Retrospective Analysis

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614364 ◽

1999 ◽

Vol 82 (10) ◽

pp. 1222-1226 ◽

Cited By ~ 16

Author(s):

W. Åberg ◽

D. Lockner ◽

C. Paul ◽

M. Holmström

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Unfractionated Heparin ◽

Malignant Disease ◽

Duration Of Treatment ◽

Post Thrombotic Syndrome ◽

Recurrent Vte

SummaryThe primary objective of this retrospective study was to describe the frequency of a post-thrombotic syndrome in 265 patients previously treated for deep venous thrombosis (DVT). The secondary objectives were to document the frequency of recurrent venous thromboembolism (VTE) and mortality, especially from malignant disease. The patients were evaluated 5-14 years after inclusion in three randomized trials comparing continuous intravenous (i. v.) infusion of unfractionated heparin (UFH) (n = 85) with a low molecular weight heparin (LMWH), dalteparin (n = 180). The median post-thrombotic score at follow-up was 2 (range 0-8). In a multiple step-wise regression analysis the post-thrombotic score was significantly higher among patients with initial proximal DVT (p = 0,0001) as compared with those who had distal DVT. A recurrent venous thromboembolic event was diagnosed in 29,4% of the patients treated with dalteparin and in 23,5% of the patients treated with UFH (ns). A secondary risk factor for venous thromboembolism and a longer duration of treatment with oral anticoagulants (OAC) were significantly associated with a lower risk for recurrent VTE, whereas malignant disease diagnosed during follow-up was associated with a higher risk. During follow-up a total of 40,7% of patients had died. No difference in total mortality or mortality from malignant disease was demonstrated between the two drugs. In conclusion, a severe post-thrombotic syndrome occured relatively infrequent. considering the long observation period. Proximal DVT was significantly associated with a more severe post-thrombotic syndrome. After 14 years follow-up, no significant differences were observed in overall mortality, mortality from malignant disease or recurrent VTE between UFH- and dalteparin-treated patients. Malignant disease was a risk factor for recurrent VTE, the presence of a secondary risk factor and a longer duration of treatment with OAC decreased the risk for recurrent VTE.

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Deep Venous Thrombosis of the Upper Limbs

Phlebology The Journal of Venous Disease ◽

10.1177/026835558800300109 ◽

1988 ◽

Vol 3 (1) ◽

pp. 63-68 ◽

Cited By ~ 10

Author(s):

Haim Gutman ◽

Meir Peri ◽

Avigdor Zelikovski ◽

Menashe Haddad ◽

Raphael Reiss

Keyword(s):

Natural History ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Surgical Approach ◽

Symptomatic Treatment ◽

Consensus Conference ◽

Natural Course ◽

Upper Limbs ◽

Fibrinolytic Agents

Deep venous thrombosis of the upper limbs is rare and represents less than 2-3% of all cases of deep venous thrombosis. Reviewing our series of 25 patients we decided that follow-up and symptomatic treatment produce acceptable results, since the disease has a benign natural history. Fibrinolytic agents administered under strict limitations (The Consensus Conference 1980, Ann Int Med) are efficient in early cases, but its ability to change the natural course of the disease has not been proved. Surgical approach should be reserved for cases with secondary ischaemia and/or a resectable extraluminal mass.

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Prevention of Recurrent Deep Venous Thrombosis with Indobufen. A 3-Year Follow-up Study Using Color Duplex Scanning

Angiology ◽

10.1177/000331979304400410 ◽

1993 ◽

Vol 44 (4) ◽

pp. 328-331 ◽

Cited By ~ 2

Author(s):

G. Belcaro ◽

B.M. Errichi ◽

P. De Simone

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Duplex Scanning ◽

Follow Up Study

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Evaluation of the Interpretation of Serial Ultrasound Examinations in the Diagnosis of Deep Venous Thrombosis in Children: A Retrospective Cohort Study

Canadian Association of Radiologists Journal ◽

10.1016/j.carj.2013.09.002 ◽

2014 ◽

Vol 65 (3) ◽

pp. 218-224 ◽

Cited By ~ 4

Author(s):

Michael Stamm ◽

Anna Zavodni ◽

Lesley Mitchell ◽

John Ross Bonanni ◽

Michelle Noga

Keyword(s):

Cohort Study ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Error Rate ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Clinical Information ◽

Imaging Findings ◽

Imaging Results

Purpose To assess ultrasound intrascan variability and the potential error rate of serial ultrasounds in the diagnosis of deep venous thrombosis in children. Methods A retrospective cohort review of imaging results of children having at least 3 serial ultrasound examinations of the same region within a 2-month period. The results were interpreted as either (1) inadequately visualized or (2) the absence or presence of deep venous thrombosis, and were categorized by location. Serial imaging findings then were further categorized based on results and clinical information. Results Sixty-four patients and 157 vessel segments were included in the study. Deep venous thrombosis was documented in 58 patients. Concordant results were observed in 26 patients (40.1%), clot resolution in 17 patients (26.6%), clot formation in 12 patients (18.8%), and discordant results in 9 patients (14%). Twenty-one of 64 patients (32.8%) had at least 1 vessel inadequately imaged. Conclusions The inconsistency of serial ultrasound results in up to 25% of patients calls attention to the potential inaccuracy of ultrasound for diagnosis and follow-up of deep venous thrombosis in children. The high proportion of patients with at least 1 inadequately visualized vessel also highlights the limitation of ultrasound in the diagnosis of pediatric deep venous thrombosis.

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Extravascular Masses Masquerading as Deep Venous Thrombosis

Phlebology The Journal of Venous Disease ◽

10.1177/026835559300800406 ◽

1993 ◽

Vol 8 (4) ◽

pp. 158-161 ◽

Cited By ~ 1

Author(s):

O. Thulesius ◽

A. Thurin

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Duplex Ultrasound ◽

Signs And Symptoms ◽

Clinical Physiology ◽

Characteristic Appearance ◽

Non Invasive ◽

The Right ◽

Symptoms And Signs ◽

Made In

Objective: To determine the incidence and characteristics of extravascular masses (EVM) giving rise to symptoms and signs of deep venous thrombosis (DVT). Design and technique: Routine ultrasound colour duplex scanning during a 6-month period. Patients: Three hundred and two inpatients and outpatients investigated on suspicion of DVT. Setting: Department of Clinical Physiology, which is the central non-invasive diagnostic unit of the county. Results: A diagnostis of DVT was made in 33%. EVM were detected in 14 patients (5%). In most cases the characteristic appearance on scanning was spindle-shaped (like a ‘mouse’) and mostly confined to the upper calf. These EVM were regarded as intramuscular haematoma or ruptured popliteal cysts. Conclusion: EVM of the leg are (1) a frequent cause of ‘pseudothrombosis' and can positively be identified by duplex ultrasound scanning: (2) most frequently found in the medial aspect of the right calf; and (3) often detected in patients with rheumatoid arthritis or patients on anticoagulant therapy and may give rise to signs and symptoms identical to DVT.

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A Multicenter Randomized Placebo Controlled Trial of Compression Stockings to Prevent the Post-Thrombotic Syndrome After Proximal Deep Venous Thrombosis: The S.O.X. Trial

Blood ◽

10.1182/blood.v120.21.393.393 ◽

2012 ◽

Vol 120 (21) ◽

pp. 393-393 ◽

Cited By ~ 3

Author(s):

Susan R. Kahn ◽

Stan Shapiro ◽

Phil S Wells ◽

Marc A. Rodger ◽

Michael J. Kovacs ◽

...

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Cumulative Incidence ◽

Research Funding ◽

Primary Outcome ◽

Controlled Trial ◽

Event Analysis ◽

Time To Event ◽

Compression Stockings

Abstract Abstract 393 Background: The post-thrombotic syndrome (PTS) is a burdensome, costly complication of deep venous thrombosis (DVT). Investigating strategies to prevent PTS is important, as treatments for PTS are limited. To date, randomized trials of elastic compression stockings (ECS) to prevent PTS were small, single-center, none used a placebo control and results are conflicting. Objective: To determine whether ECS, compared with inactive (placebo) stockings, are effective to prevent PTS in patients with proximal DVT. Methods: We conducted a multicenter (24 centres, Canada and U.S.) randomized placebo controlled trial of active ECS (A-ECS) vs. placebo ECS (P-ECS) to prevent PTS after a first, symptomatic proximal DVT. A-ECS were knee length 30–40 mm Hg (Class II) graduated ECS. P-ECS were manufactured to look identical to A-ECS but lacked therapeutic compression. Stockings were mailed directly to patients and worn on the DVT-affected leg daily for up to 2 years. Patients did not wear their stockings at study follow-up visits (1, 6, 12, 18 and 24 months) to maintain study personnel blinding. The primary study outcome, PTS, was diagnosed at or after the 6 month visit using the Ginsberg measure (leg pain and swelling of 3 1 month duration and typical in character: worse end of day or after prolonged sitting/standing and improved after rest/leg elevation). All PTS diagnoses were confirmed by the local study physicians. Secondary outcomes were incidence and severity of PTS using the Villalta scale, venous ulcers, VTE recurrence and death from VTE. A sample size of 800 patients was targeted based on a hypothesized cumulative incidence of the primary outcome of 30% in P-ECS vs. 20% in A-ECS, 2-tailed a of 0.05 and 80% power, and anticipated 25% rate of death/withdrawal/lost-to-follow-up. Using a modified intent to treat approach, we performed a time-to-event analysis using a Cox proportional hazards model adjusted for center to calculate hazard ratios (HR) and 95% confidence intervals (CI) to compare rates of the primary outcome in A-ECS vs. P-ECS. A similar time-to-event analysis was performed for Villalta PTS (Villalta score ≥ 5 at or after the 6 month visit). Results: From 2004–2010, 398 patients were randomized to A-ECS and 408 to P-ECS. 3 patients found to be ineligible soon after randomization were excluded from the analysis. Median time from DVT diagnosis to randomization was 4 days. Baseline features were similar in the 2 groups; overall, 60% were male, mean age was 55 years, and most proximal extent of DVT was iliac or femoral vein in 70% and popliteal vein in 30% of patients. The cumulative incidence of PTS (primary outcome) by 750 days was 14.8% in A-ECS vs. 12.3% in P-ECS (Figure) (HRadj 1.17; 95% CI 0.75–1.81; p=0.49). The cumulative incidence of Villalta PTS (secondary outcome) was 52.1% in A-ECS vs. 52.2% in P-ECS (HRadj 0.96; 95% CI 0.78–1.19; p=0.69). Additional outcomes were also similar in the two intervention groups (Table). Rates of loss to follow-up (5.5% vs. 5.4%) and withdrawal (8.3% vs. 9.1%) were similar in A-ECS and P-ECS. Overall, ∼70% of patients in both groups continued the intervention throughout study follow-up, and of these, >80% of patients in both groups reported use for ≥ 3 days per week. Conclusions: In a large randomized placebo-controlled trial, ECS did not prevent the occurrence of PTS after a first proximal DVT and did not influence the severity of PTS or rate of recurrent VTE. The reported benefits of ECS to prevent PTS in some prior studies could be due, at least in part, to bias from open-label design. Whether ECS may be of benefit to manage symptoms of established PTS should be evaluated in future studies. Disclosures: Kahn: NIH: Research Funding; Canadian Institutes for Health Research: Research Funding; Sigvaris: Research Funding.

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