Tone Enden

Catheter‐directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short‐term patency

Summary.  Background: Approximately one in four patients with acute proximal deep vein thrombosis (DVT) given anticoagulation and compression therapy develop post‐thrombotic syndrome (PTS). Accelerated removal of thrombus by thrombolytic agents may increase patency and prevent PTS. Objectives: To assess short‐term efficacy of additional catheter‐directed thrombolysis (CDT) compared with standard treatment alone. Patients and methods: Open, multicenter, randomized, controlled trial. Patients (18–75 years) with iliofemoral DVT and symptoms < 21 days were randomized to receive additional CDT or standard treatment alone. After 6 months, iliofemoral patency was investigated using duplex ultrasound and air‐plethysmography assessed by an investigator blinded to previous treatment. Results: One hundred and three patients (64 men, mean age 52 years) were allocated additional CDT (n = 50) or standard treatment alone (n = 53). After CDT, grade III (complete) lysis was achieved in 24 and grade II (50%–90%) lysis in 20 patients. One patient suffered major bleeding and two had clinically relevant bleeding related to the CDT procedure. After 6 months, iliofemoral patency was found in 32 (64.0%) in the CDT group vs. 19 (35.8%) controls, corresponding to an absolute risk reduction (RR) of 28.2% (95% CI: 9.7%–46.7%; P = 0.004). Venous obstruction was found in 10 (20.0%) in the CDT group vs. 26 (49.1%) controls; absolute RR 29.1% (95% CI: 20.0%–38.0%; P = 0.004). Femoral venous insufficiency did not differ between the two groups. Conclusions: After 6 months, additional CDT increased iliofemoral patency from 36% to 64%. The ongoing long‐term follow‐up of this study will document whether patency is related to improved functional outcome.

Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial

BACKGROUND Post-thrombotic syndrome is a common complication after acute proximal deep vein thrombosis (DVT) and is associated with reduced quality of life and a substantial cost burden. In the 2-year results of the CaVenT study, additional catheter-directed thrombolysis reduced the risk of post-thrombotic syndrome by 14% compared with conventional therapy, but did not affect quality of life. In this study we report results at the 5-year follow-up, aiming to assess whether findings for post-thrombotic syndrome and quality of life have persisted. METHODS Between Jan 3, 2006, and Dec 22, 2009, we recruited patients aged 18-75 years with a first-time high proximal leg DVT from 20 hospitals in the Norwegian southeastern health region. With sealed envelopes, participants were randomly assigned (1:1) to standard treatment with compression stockings and anticoagulants (control group) or to standard treatment plus catheter-directed thrombolysis with alteplase within 21 days from symptom onset. Pre-specified outcomes in this analysis were post-thrombotic syndrome at 5 years as assessed with the Villalta score and scores for quality of life at 5 years with EQ-5D and the disease-specific VEINES-QOL/Sym. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00251771. FINDINGS At 5 year follow-up (last date Oct 14, 2014), data were available for 176 patients (84% of the 209 patients originally randomised)--87 originally assigned to catheter-directed thrombolysis and 89 originally assigned to the control group. 37 patients (43%; 95% CI 33-53) allocated to catheter-directed thrombolysis developed post-thrombotic syndrome, compared with 63 (71%; 95% CI 61-79) allocated to the control group (p<0·0001), corresponding to an absolute risk reduction of 28% (95% CI 14-42) and a number needed to treat of 4 (95% CI 2-7). Four (5%) patients assigned to catheter-directed thrombolysis and one (1%) to standard treatment had severe post-thrombotic syndrome (Villalta score ≥ 15 or presence of an ulcer). Quality-of-life scores with either assessment scale did not differ between the treatment groups. INTERPRETATION Additional catheter-directed thrombolysis resulted in a persistent and increased clinical benefit during follow-up for up to 5 years, supporting the use of additional catheter-directed thrombolysis in patients with extensive proximal DVT. However, allocation to this therapy did not lead to better quality of life. The optimal endovascular thrombolytic approach needs further investigation. FUNDING Southeastern Norway Regional Health Authority, the Research Council of Norway, University of Oslo, Oslo University Hospital.

Polar expression of tissue factor in human umbilical vein endothelial cells

Endothelial cells grown on filters developed junctional complexes that reduced diffusional transport and increased electrical resistance over the cell layer. Induction of tissue factor by recombinant interleukin-1 beta led to a highly polarized tissue factor expression on the apical cell surface only. After prolonged growth to allow deposition of matrix, removal of the endothelial cells by collagenase or by 0.1 mol/L NH4OH left behind some cellular material as well as tissue factor, which was only detectable in the upper compartment. A human bladder carcinoma cell line, which does not form tight junctions and expresses tissue factor constitutively, showed essentially no polarity. Endothelial cell secretory compounds like von Willebrand factor, tissue plasminogen activator, and plasminogen activator inhibitor-1 were constitutively released to both sides. The added secretion due to recombinant interleukin-1 beta stimulation of the endothelial cells observed for von Willebrand factor and tissue plasminogen activator was, however, localized to the apical surface. The availability of tissue factor on the luminal surface of endothelial cells, ie, allowing contact with factor VII in the flowing blood, has potentially very significant pathophysiological consequences.

Determinants of early and long-term efficacy of catheter-directed thrombolysis in proximal deep vein thrombosis.

PURPOSE Catheter-directed thrombolysis (CDT) for proximal deep vein thrombosis (DVT) effectively enhances clot removal and recently has been shown to reduce the development of postthrombotic syndrome (PTS). This study was performed to identify potential markers for early and long-term efficacy of CDT, adverse events, and their interrelationship. MATERIALS AND METHODS Patients aged 18-75 years (mean, 54 y; 33 women) with first-time proximal DVT and symptoms up to 21 days were included in subanalyses in an open, multicenter, randomized, controlled trial. Early efficacy was assessed with a thrombus score based on daily venography. Six-month and 2-year follow-up included iliofemoral patency assessed with duplex ultrasound and air plethysmography, and PTS was assessed with the Villalta scale. RESULTS A mean clot resolution of 82%±25 was achieved in 92 patients. Successful lysis (ie,≥50%) was obtained in 83 patients. Early efficacy was equal for femoral and iliofemoral thrombus and not related to thrombus load before CDT, symptom duration, or predisposing risk factors. Lower thrombus score at completion of CDT was associated with increased patency at 24 months (P = .040), and increased patency after 6 and 24 months was correlated with reduced development of PTS after 24 months (P<.001). Bleeding complications were mainly related to the puncture site, and popliteal vein access led to fewer bleeding incidents. CONCLUSIONS Comp, this is a Clinical Study article, so, as noted on the TOC, the Conclusions section of the abstract gets listed on the TOC. CDT via popliteal access was safe, effectively removed clots, and restored iliofemoral patency. Preprocedure evaluation did not identify patients who did not benefit from treatment. Early efficacy and follow-up patency are of importance to reduce the risk for PTS.

Health-related quality of life after catheter-directed thrombolysis for deep vein thrombosis: secondary outcomes of the randomised, non-blinded, parallel-group CaVenT study

Objectives To investigate whether additional catheter-directed thrombolysis (CDT) improves long-term quality of life (QOL) compared with standard treatment with anticoagulation and compression stockings alone in patients with proximal deep vein thrombosis (DVT). Design Open-label randomised controlled trial. Setting 19 Hospitals in the Norwegian southeastern health region. Participants Patients (18–75 years) with a high proximal DVT, symptoms <21 days and no increased risk of bleeding were eligible. 189 of 209 recruited patients completed 24 months of follow-up. Interventions Participants were randomised to additional CDT with alteplase for 1–4 days or to standard treatment only with 6 months of anticoagulation and 24 months of compression stockings. Primary and secondary outcome measures Planned secondary outcome measures included QOL as assessed with the generic instrument EQ-5D and the disease-specific instrument VEINES-QOL/Sym. Primary outcome measure was post-thrombotic syndrome (PTS) after 24 months. Results After 24 months there were no differences in QOL between the additional CDT and standard treatment arms; mean difference for the EQ-5D index was 0.04 (95% CI −0.10 to 0.17), for the VEINES-QOL score 0.2 (95% CI −2.8 to 3.0) and for the VEINES-Sym score 0.5 (95% CI −2.4 to 3.4; p values>0.37). Independent of treatment arms, patients with PTS had poorer outcomes than patient without PTS; mean difference for EQ-5D was 0.09 (95% CI 0.03 to 0.15), for VEINES-QOL score 8.6 (95% CI 5.9 to 11.2) and for VEINES-Sym score 9.8 (95% CI 7.3 to 12.3; p values<0.001). Conclusions QOL did not differ between patients treated with additional CDT compared with standard treatment alone. Patients who developed PTS reported poorer QOL and more symptoms than patients without PTS. QOL should be included as an outcome measure in clinical studies on patients at risk of PTS. Trial registration NCT00251771

Visualization of deep veins and detection of deep vein thrombosis (DVT) with balanced turbo field echo (b-TFE) and contrast-enhanced T1 fast field echo (CE-FFE) using a blood pool agent (BPA).

To assess image quality, vessel visualization, preliminary diagnostic properties, and interobserver variability of a novel balanced turbo field echo (b‐TFE) sequence and contrast‐enhanced T1 fast field echo (CE‐FFE) sequence with blood pool agent (BPA).

Long-term quality of life after pregnancy-related deep vein thrombosis and the influence of socioeconomic factors and comorbidity.

Summary.  Background: Little is known about the long‐term impact of pregnancy‐related deep vein thrombosis (DVT) of the lower limbs. Objectives: To evaluate the long‐term consequences of pregnancy‐related DVT by assessment of self‐reported, disease‐specific quality of life (QOL) and symptom severity using the Venous Insufficiency Epidemiological and Economic Study (VEINES)‐QOL/Sym questionnaire, and to investigate the influence of socioeconomic factors and comorbidity. Patients/Methods: In this cross‐sectional case–control study, 313 women with validated pregnancy‐related DVT and 353 controls completed a comprehensive questionnaire, including the disease‐specific VEINES‐QOL/Sym questionnaire. After exclusion of DVT outside the lower limbs and missing scores, the study population comprised 208 patients and 347 controls. A VEINES‐QOL/Sym score < the 25th percentile was defined as a clinically relevant reduced outcome compared with scores ≥ the 50th percentile. Predictors for low scores were identified in multivariate logistic regression models. Results: Cases reported lower mean VEINES‐QOL/Sym scores than controls, 45.6/45.4 vs. 52.8/52.7, respectively (P < 0.001), and QOL among cases was still reduced compared with controls when adjusted for possible confounders. Low education was an independent predictor for both low VEINES‐QOL and VEINES‐Sym scores, and in addition being married/cohabitating predicted low VEINES‐Sym scores. Conclusions: Long‐term QOL and symptom scores as assessed with the VEINES‐QOL/Sym questionnaire were lower in women with previous pregnancy‐related DVT than in controls, and also when adjusted for possible confounders. By logistic regression, low education was an independent predictor for low scores. This supports the use of the VEINES‐QOL/Sym questionnaire in studies on pregnancy‐related DVT.

Recurrent venous thrombosis, post-thrombotic syndrome and quality of life after catheter-directed thrombolysis in severe proximal deep vein thrombosis.

W. GHA NIMA,* I . W. K LEVEN ,* T . ENDEN, A. ROSALES ,§ H . S . WIK ,– L . PEDERSTA D, ** P . A . HOLME and P . M. SANDSET– *Department of Medicine, Østfold Hospital Trust Fredrikstad, Fredrikstad; Departments of Haematology, Radiology and §Vascular Surgery, Oslo University Hospital, Oslo; –Institute of Clinical Medicine, University of Oslo, Oslo; and **Department of Radiology, Østfold Hospital Trust Fredrikstad, Fredrikstad, Norway

Symptom burden and job absenteeism after treatment with additional catheter-directed thrombolysis for deep vein thrombosis

Introduction Additional catheter-directed thrombolysis (CDT) for acute deep vein thrombosis (DVT) reduces long-term postthrombotic syndrome and is likely to represent a cost-effective alternative treatment compared to the standard treatment of anticoagulation and elastic compression stockings. Accelerated thrombus resolution has also been suggested to improve symptoms and patient function in the acute phase. We aimed to investigate whether additional CDT led to fewer symptoms and job absenteeism during the first 6 months after initiation of DVT treatment compared to standard treatment alone. Methods The Catheter-directed Venous Thrombolysis (CaVenT) study was a multicenter open label, randomized controlled trial of patients ages 18 years to 75 years with a verified high proximal DVT, <21 days of symptoms, and no apparent bleeding risk. Patients were allocated to additional CDT or to standard treatment only. Symptoms were assessed at baseline and at 6 months using items from the generic and disease-specific quality of life questionnaires EQ-5D and VEINES-QOL/Sym, respectively. Individual data on sickness benefits related to venous thromboembolic disease were obtained from the national welfare service. Results A total of 90 patients allocated additional CDT and 99 control patients completed long-term follow-up and were included in the analyses. Twenty-four in the CDT arm and 40 controls received sick leave (P = 0.046). When considering working patients only (54 in the CDT arm and 72 controls) this difference was no longer statistically significant. Mean duration of job absenteeism was 86.4 days (95% confidence interval 59.4–113.5) in the CDT arm and 60.1 days (95% confidence interval 42.3–77.8) in controls (P = 0.072). After 6 months, more controls experienced frequent swelling of the leg compared with those allocated to CDT (47 [49.0%] patients versus 25 [29.4%] patients, respectively, [P = 0.007]). Conclusion There are limitations to our data, but the findings indicate improved symptom relief and less frequent job absenteeism in patients treated with additional CDT; this expands upon previously established benefits from this treatment.

Benign metastasizing pleomorphic adenoma in liver mimicking synchronic metastatic disease from colorectal cancer: a case report with emphasis on imaging findings

Pleomorphic adenoma of the parotid gland with metastases to the liver is a rare etiology of focal liver lesions, and there are no described pathognomonic imaging features. We report a patient who presented with a newly diagnosed rectal cancer and multiple cystic liver lesions suspicious of mucinous synchronous liver metastases. Following chemotherapy no reduction in the number or size of the liver lesions was observed. The patient was re-evaluated and a biopsy of a lesion was performed. The specimen showed a metastasis from a pleomorphic adenoma of the parotid gland for which the patient had been treated 20 years earlier. The case illustrates how a thorough medical history can be crucial when a standard diagnostic imaging workup for colorectal cancer metastases is uncertain, and how a biopsy, though regarded as contraindicated due to the risk of tumor cell dissemination, can be required to secure a correct diagnosis.