Predictors of long-term post-thrombotic syndrome following high proximal deep vein thrombosis: a cross-sectional study.

BACKGROUND: Post-thrombotic syndrome (PTS) is a frequent chronic complication of proximal deep vein thrombosis (DVT) of the lower limb, but predictors of PTS are not well established. We aimed to examine predictors of PTS in patients with long-term PTS following proximal DVT. METHODS: During 2006-09, 209 patients with a first time acute upper femoral or iliofemoral DVT were randomized to receive either additional catheter-directed thrombolysis or conventional therapy alone. In 2017, the 170 still-living participants were invited to participate in a cross-sectional follow-up study. In the absence of a gold standard diagnostic test, PTS was defined in line with clinical practice by four mandatory, predefined clinical criteria: 1. An objectively verified DVT; 2. Chronic complaints (> 1 month) in the DVT leg; 3. Complaints appeared after the DVT; and 4. An alternative diagnosis was unlikely. Possible predictors of PTS were identified with multivariate logistic regression. RESULTS: Eighty-eight patients (52%) were included 8-10 years following the index DVT, and 44 patients (50%) were diagnosed with PTS by the predefined clinical criteria. Younger age and higher baseline Villalta score were found to be independent predictors of PTS, i.e., OR 0.96 (95% CI, 0.93-0.99), and 1.23 (95% CI, 1.02-1.49), respectively. Lack of iliofemoral patency at six months follow-up was significant in the bivariate analysis, but did not prove to be significant after the multivariate adjustments. CONCLUSIONS: In long-term follow up after high proximal DVT, younger age and higher Villalta score at DVT diagnosis were independent predictors of PTS.

Radiology response in the emergency department during a mass casualty incident: a retrospective study of the two terrorist attacks on 22 July 2011 in Norway.

OBJECTIVES: To describe the use of radiology in the emergency department (ED) in a trauma centre during a mass casualty incident, using a minimum acceptable care (MAC) strategy in which CT was restricted to potentially severe head injuries. METHODS: We retrospectively studied the initial use of imaging on patients triaged to the trauma centre following the twin terrorist attacks in Norway on 22 July 2011. RESULTS: Nine patients from the explosion and 15 from the shooting were included. Fourteen patients had an Injury Severity Score >15. During the first 15 h, 22/24 patients underwent imaging in the ED. All 15 gunshot patients had plain films taken in the ED, compared to three from the explosion. A CT was performed in 18/24 patients; ten of these were completed in the ED and included five non-head CTs, the latter representing deviations from the MAC strategy. No CT referrals were delayed or declined. Mobilisation of radiology personnel resulted in a tripling of the staff. CONCLUSIONS: Plain film and CT capacity was never exceeded despite deviations from the MAC strategy. An updated disaster management plan will require the radiologist to cancel non-head CTs performed in the ED until no additional MCI patients are expected. KEY POINTS: • Minimum acceptable care (MAC) should replace normal routines in mass casualty incidents. • MAC implied reduced use of imaging in the emergency department (ED). • CT in ED was restricted to suspected severe head injuries during MAC. • The radiologist should cancel all non-head CTs in the ED during MAC.

Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial.

BACKGROUND: Conventional anticoagulant treatment for acute deep vein thrombosis (DVT) effectively prevents thrombus extension and recurrence, but does not dissolve the clot, and many patients develop post-thrombotic syndrome (PTS). We aimed to examine whether additional treatment with catheter-directed thrombolysis (CDT) using alteplase reduced development of PTS. METHODS: Participants in this open-label, randomised controlled trial were recruited from 20 hospitals in the Norwegian southeastern health region. Patients aged 18-75 years with a first-time iliofemoral DVT were included within 21 days from symptom onset. Patients were randomly assigned (1:1) by picking lowest number of sealed envelopes to conventional treatment alone or additional CDT. Randomisation was stratified for involvement of the pelvic veins with blocks of six. We assessed two co-primary outcomes: frequency of PTS as assessed by Villalta score at 24 months, and iliofemoral patency after 6 months. Analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00251771. FINDINGS: 209 patients were randomly assigned to treatment groups (108 control, 101 CDT). At completion of 24 months' follow-up, data for clinical status were available for 189 patients (90%; 99 control, 90 CDT). At 24 months, 37 (41·1%, 95% CI 31·5-51·4) patients allocated additional CDT presented with PTS compared with 55 (55·6%, 95% CI 45·7-65·0) in the control group (p=0·047). The difference in PTS corresponds to an absolute risk reduction of 14·4% (95% CI 0·2-27·9), and the number needed to treat was 7 (95% CI 4-502). Iliofemoral patency after 6 months was reported in 58 patients (65·9%, 95% CI 55·5-75·0) on CDT versus 45 (47·4%, 37·6-57·3) on control (p=0·012). 20 bleeding complications related to CDT included three major and five clinically relevant bleeds. INTERPRETATION: Additional CDT should be considered in patients with a high proximal DVT and low risk of bleeding. FUNDING: South-Eastern Norway Regional Health Authority; Research Council of Norway; University of Oslo; Oslo University Hospital.

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.

Arterial events in cancer patients treated with apixaban for venous thrombosis.

INTRODUCTION: In a recent interventional study of cancer patients with newly diagnosed venous thrombosis (VT), we found a high risk of arterial thrombotic events (AT) during treatment with therapeutic doses of apixaban. METHODS: Total 298 cancer patients with VT received apixaban as treatment and secondary prophylaxis for up to 36 months. AT was registered as a serious adverse event, and this is a post hoc analysis of risk factors for AT. Clinical risk factors and concomitant medication were assessed through odds ratios (OR) with 95 % confidence interval using multivariate logistic regression. Biomarkers were assessed by non-parametric testing. RESULTS: AT occurred in 16/298 patients (5.4 %, 95 % confidence interval (CI) 3.1-8.6 %). Median leucocyte count at baseline was higher in patients with AT compared with patients without AT (11 vs. 6.8·109/L, p < 0.01). Clinical factors associated with AT were pancreatic cancer (OR 13.7, 95 % CI 4.3-43.1), ovarian cancer (OR 19.3, 95 % CI 2.3-164.4), BMI <25 percentile (OR 3.1, 95 % CI 1.1-8.8) and previous VT (OR 4.4, 95 % CI 1.4-13.7). Pancreatic cancer had a cumulative incidence of AT of 36 % compared with 0.8 % for all other cancers at 6 months (p < 0.01). Non-steroidal anti-inflammatory drugs (OR 4.9, 95 % CI 1.0-26) and antiplatelet treatment (OR 3.8, 95 % CI 1.2-12.2) were associated with AT. CONCLUSION: In cancer patients with apixaban treated VT, pancreatic cancer was strongly associated with AT. In addition, ovarian cancer, BMI < 25 percentile, previous VT, antiplatelet treatment, non-steroidal anti-inflammatory drug use and high leucocyte count at baseline were associated with AT. The CAP study is registered with the unique identifier NCT02581176 in ClinicalTrials.gov.

Low dose apixaban as secondary prophylaxis of venous thromboembolism in cancer patients - 30 months follow-up.

BACKGROUND: There are no data on the effect of low-dose anticoagulation as secondary prophylaxis for venous thromboembolism (VTE) in cancer patients. We assessed the efficacy and safety of low-dose apixaban for 30 months, after initial 6 months of full-dose treatment. METHODS: We included 298 patients with cancer and any type of VTE in a single arm interventional clinical trial. All patients were treated with full-dose apixaban (5 mg twice daily) for 6 months. Total 196 patients with active cancer after 6 months treatment continued with apixaban 2.5 mg twice daily for another 30 months. The main endpoints were recurrent VTE, major bleeding and clinically relevant non-major bleeding. RESULTS: During the 30 months of treatment with low-dose apixaban 14 (7.6%; 95% confidence interval (CI) 4.0%-11.7%) patients experienced recurrent VTE, six (3.1%; 95% CI 1.1%-6.5%) experienced major bleeding and 16 (8.1%, 95% CI: 4.7%-12.8%) experienced clinically relevant non-major bleeding. The incidence rate per person month of recurrent VTE was 0.8% (95% CI 0.41-1.6) at 2-6 months with full-dose apixaban, and 1.0% (95% CI 0.5-1.9) at 7-12 months with low-dose apixaban. The incidence rate of major bleeding was 1.1% (95% CI 0.6-2.0) at 2-6 months, and 0.3% (95% CI 0.1-1.0) at 7-12 months. Between 12 and 36 months the incidence rate of recurrent VTE and major bleedings remained low. CONCLUSION: Dose reduction of apixaban to 2.5 mg twice daily seems safe after 6 months of full-dose treatment. After 12 months the incidence rate of recurrent VTE and major bleeding remained low.

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).

PURPOSE: 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). MATERIALS AND METHODS: A total of 15 healthy volunteers and six patients with ultrasound-verified proximal deep vein thrombosis (DVT) were examined from the inferior vena cava (IVC) to the proximal calf veins. RESULTS: The great majority of deep veins were completely visualized on both sequences. In healthy volunteers the IVC was completely visualized in five b-TFE and 11 CE-FFE scans, and partially in seven b-TFE and four CE-FFE scans (P = 0.008). Poorest image quality was in the pelvis. Contrast-to-noise ratio (CNR) was higher on b-TFE compared to CE-FFE, with significant difference in calf images (P = 0.036). Sensitivity was 100% for proximal DVT with both methods. Specificity was 70% (CE-FFE) and 80% (b-TFE) for proximal femoral DVT; 100% in distal femoral. Interobserver reliability was kappa 1.0 (b-TFE), 0.9 (CE-FFE) for proximal, and overall poor for distal DVT. CONCLUSION: Contrast-enhancement did not add valuable information in visualizing deep veins of the lower limbs compared to b-TFE, though the IVC was slightly better visualized. Diagnostic properties and interobserver reliability of both sequences were good for proximal DVT and poor for distal DVT.

Thrombosis and bleedings in a cohort of cancer patients treated with apixaban for venous thromboembolism.

INTRODUCTION: The direct oral anti-coagulants (DOAC) edoxaban and rivaroxaban are suggested treatment alternatives for cancer-associated venous thromboembolism (VTE) together with low molecular-weight heparins. New studies indicate that the DOAC apixaban also is an option for cancer-associated VTE. The current study assessed recurrent VTE, arterial thrombosis, bleedings and adverse events in a cohort of apixaban treated cancer patients with VTE. MATERIALS AND METHODS: Single-arm, interventional study of apixaban as treatment of cancer-associated VTE. Inclusion criteria were cancer with objectively verified VTE. Patients received apixaban 10 mg bid for seven days, then 5 mg bid for six months. Primary efficacy and safety outcomes were recurrent VTE and bleeding respectively. This trial is registered with ClinicalTrials.gov identifier NCT02581176. RESULTS: We recruited 298 cancer patients with VTE. During six months treatment, recurrent VTE or death related to VTE occurred in 12 patients (4.0%, 95% confidence interval (CI) 2.1-6.9%). Major bleeding occurred in 16 patients (5.4%, 95% CI 2.8-7.9), most frequently gastrointestinal bleeding. There were no overrepresentation of major bleedings among patients with gastrointestinal cancer (7/126, 5.5%, 95% CI 2.3-11%). Twenty-six patients experienced one or more clinically relevant non-major bleedings (8.9%, 95% CI 5.5-12%). Twelve patients had arterial thrombosis (4.0%, 95% CI 2.1-6.9%), of which the majority were strokes in patients with pancreatic cancer. Death occurred in 35 patients (12%, 95% CI 8.3-16%). CONCLUSION: The frequency of recurrent VTE and major bleedings are in line with other studies on apixaban in cancer-associated VTE. Arterial thrombosis was a frequent serious adverse event.

Assessing burden of illness following acute deep vein thrombosis: data quality, reliability and validity of the Norwegian version of VEINES-QOL/Sym, a disease-specific questionnaire.

The data quality, reliability and validity of the Norwegian version of VEINES-QOL/Sym were assessed in 74 patients with deep vein thrombosis (DVT). This patient-reported questionnaire produces two scale scores of venous disease-specific quality of life and venous symptoms. Items had low levels of missing data. Item-total correlations ranged from 0.41 to 0.78 with the exception of 0.29 for the symptom item 'night cramps'. Internal consistency was supported by Cronbach's alpha of 0.88 and 0.94 for VEINES-Sym and VEINES-QOL, respectively. Test-retest reliability assessed for 40 patients gave intraclass correlation coefficients of 0.83 and 0.88 for VEINES-Sym and VEINES-QOL, respectively. Assessment of correlation between the two scales and other clinical measures supports the construct validity of the scales. The results indicate acceptable internal consistency, test-retest reliability and validity of the Norwegian version of the VEINES-QOL/Sym questionnaire in patients with DVT. The results follow those of previous studies, and support the use of VEINES-QOL/Sym in the evaluation of patient outcomes and burden of illness in clinical studies of venous thrombosis.

Limitations of the Villalta scale in diagnosing post-thrombotic syndrome.

INTRODUCTION: The Villalta scale is currently the recommended tool for diagnosing post-thrombotic syndrome (PTS) in clinical studies, but there is concern that the sensitivity and specificity of the scale might be low. We aimed to evaluate the diagnostic accuracy of the Villata scale using criteria in line with clinical practice as a reference. MATERIAL AND METHODS: We invited patients with a history of proximal DVT during 2006-09 to participate in a cross-sectional follow-up study of long-term complications after DVT. PTS was diagnosed by the Villalta scale, and by the following four mandatory and predefined clinical criteria used as a reference for PTS: 1. Objectively verified DVT; 2. chronic complaints (>1 month) in the DVT leg; 3. complaints appeared after the DVT; and 4. an alternative diagnosis was unlikely. RESULTS: We included 88 of 170 eligible patients (52%). With our clinical criteria as a reference the sensitivity and specificity of the Villalta scale for diagnosing PTS were 75% (95% CI 60-87%) and 66% (95% CI 50-80%), respectively. Fifteen patients were diagnosed with PTS by the Villalta scale only. These patients more often experienced pain or had comorbidity that could explain their leg symptoms and signs. Eleven patients diagnosed with PTS by the clinical criteria only, had more fluctuating heaviness and edema. CONCLUSIONS: Our findings indicate that the diagnostic accuracy of the Villalta scale has limitations. Incorporating chronicity, whether the leg problems appeared following the DVT, fluctuations of heaviness and edema, and comorbidity in PTS assessment may improve the diagnostic accuracy.

Does the Villalta scale capture the essence of postthrombotic syndrome? A qualitative study of patient experience and expert opinion.

BACKGROUND: The Villalta scale is recommended for diagnosing and grading of postthrombotic syndrome (PTS) in clinical studies, but with limitations in specificity and sensitivity. OBJECTIVES: To explore the typical complaints of PTS through patients experience and expert opinion and relate this to the items of the Villalta scale. PATIENTS/METHODS: A qualitative study design with focus group interviews including patients with PTS and health care workers experienced in PTS patient care. RESULTS: Typical PTS complaints were reflected within four main domains: (a) agonizing discomforts; patients without venous ulcers often described other discomforts than pain; (b) skin changes; these were common and sometimes present before deep vein thrombosis (DVT). Except for venous ulcers, skin changes were considered of less importance; (c) fluctuating heaviness and swelling during the day and with activity; (d) post-DVT concerns; fear of DVT recurrence, health services failing to meet the patients' expectations, and psychological and social restrictions. These findings are not necessarily captured or well reflected in the Villalta scale. CONCLUSION: Our findings indicate that the Villalta scale does not capture typical PTS complaints or their importance to the patients. A revision of the diagnosis and grading should be considered.