Towards improvement in deep vein thrombosis : Studies on diagnostic MRI, thrombolytic therapy, and quality of life

Background: Standard treatment for deep vein thrombosis includes anticoagulation and compression therapy. Accelerated lysis of venous thrombus by additional catheter-directed thrombolysis is suggested to reduce the development of postthrombotic syndrome. Large scale randomized controlled trials with long-term follow-up are needed to evaluate additional thrombolysis compared with standard treatment alone. Traditionally clinical trials on deep vein thrombosis have not employed functional outcomes with assessment of postthrombotic syndrome and quality of life, and this should be included. Routine diagnostic imaging with ultrasound for detection of acute deep vein thrombosis is not always feasible. Aims: The overall objective was to evaluate and improve diagnostic imaging and therapy of deep vein thrombosis of the lower limb with focus on catheter-directed thrombolysis and MRI. The first aim was to design and implement a well designed trial for the evaluation of additional catheter-directed thrombolysis. The second aim was translation and psychometric evaluation with assessment of data quality, reliability and validity, of a disease-specific questionnaire for patient reported quality of life following venous thrombosis of the lower limb. Final aim was to compare balanced MRI with contrast-enhanced MRI in visualisation of the deep veins and detection of acute deep vein thrombosis with ultrasound as reference method. Materials and methods: In the CaVenT Study a total of 200 patients with acute iliofemoral deep vein thrombosis will be recruited to detect a clinically relevant reduction in postthrombotic syndrome from 25 % to 10 % after 2 years. The patients are randomized to receive additional thrombolysis or standard treatment alone. The first 118 recruited patients were included in the analyses on short-term patency. Noninvasive assessment of veins, clinical assessment of postthrombotic syndrome, and patient-reported outcome on quality of life were performed after 6 and 24 months. The quality of life validation study was performed on a subset of 74 patients in the CaVenT Study using a novel Norwegian translation of the VEINES-QOL/Sym questionnaire. Balanced and contrast enhanced MRI were performed in 15 healthy volunteers and 6 patients with proximal deep vein thrombosis verified with ultrasound. Results: A psychometric evaluation of the Norwegian version of the VEINES-QOL/Sym questionnaire indicated satisfactory data quality, item-total correlations, internal consistency, test-retest reliability, and construct validity. Additional catheter-directed thrombolysis resulted in effective lysis in the great majority of patients. After 6 months venous patency was improved (64.0% vs. 35.8%) and venous obstruction was reduced (20.0% vs. 49.1%) when comparing additional thrombolysis with standard treatment alone. Venous incompetence was detected in the majority of patients, and did not differ between the two groups. Balanced and contrast-enhanced MRI techniques were comparable in visualizing the deep veins of the lower limb. Diagnostic properties and inter-observer reliability of both MRI sequences were good for proximal and poor for distal deep vein thrombosis. Conclusions: The CaVenT study is a considerable contribution towards a more evidence-based practice in the treatment of deep vein thrombosis, and future long-term results may lead to a modification of clinical guidelines. The psychometric properties of the Norwegian version of the VEINES-QOL/Sym questionnaire support its use in the evaluation of patient outcomes and burden of illness in clinical studies on deep vein thrombosis. Additional catheter-directed thrombolysis improved short-term venous patency compared to anticoagulation and compression therapy only. Both balanced and contrast-enhanced MRI may be used for the detection of proximal deep vein thrombosis in patients where ultrasound is not feasible

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

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

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

Infrainguinal inflow assessment and endovenous stent placement in iliofemoral post-thrombotic obstructions

Purpose To assess the technical success, patency, and clinical outcome, following assessment of inflow and infrainguinal endovenous stent placement in patients with iliofemoral post-thrombotic obstruction with infrainguinal involvement. Methods A retrospective analysis of 39 patients with iliofemoral post-thrombotic venous obstruction accepted for infrainguinal stent placement in the period November 2009–December 2016. The clinical status was categorized according to the Clinical Etiological Anatomical Pathophysiological (CEAP) classification and symptom severity was assessed using Venous Clinical Severity Score (VCSS). The inflow was categorized as “good”, “fair”, or “poor” depending on vein caliber and extent of post-thrombotic changes in the inflow vessel(s). Stent patency was assessed by duplex ultrasound. Median follow-up was 44 months (range 2–90 months). Results Stent placement was successful in all 39 patients. Primary patency after 24 months was 78%. Thirty of 39 patients (77%) had open stents at final follow-up. Re-interventions were performed in four patients and included catheter-directed thrombolysis (CDT) in all and adjunctive stenting in two. Twenty-eight of 39 patients (72%) reported a sustained clinical improvement. Patients with “good” inflow had better patency compared to those with “fair”/“poor” (p = 0.01). One patient experienced acute contralateral iliofemoral thrombosis; this segment was successfully treated with CDT and stenting. No other complications required intervention. Conclusion Infrainguinal endovenous stent placement was a feasible and safe treatment with good patency and clinical results, and should be considered in patients with substantial symptoms from post-thrombotic obstructions with infrainguinal involvement. Stents with good inflow have better patency and inflow assessment is essential in deciding the optimal stent landing zone