Orientador: Francisco Humberto de Abreu Maffei / Banca: Hamilton de Almeida Rollo / Banca: José Roberto Fioretto / Banca: Fausto Miranda Junior / Banca: Jorge David Aivazoglou Carneiro / Resumo: A importância do estudo da trombose venosa profunda (TVP) em crianças e adolescentes reside no impacto desta doença sobre a qualidade de vida desta população, tendo em vista sua longa expectativa de vida e a morbidade associada ao tromboembolismo venoso. Com o passar dos anos, a síndrome pós-trombótica e a recorrência podem deixar sequelas que vão desde dor crônica nos membros, edema e até úlceras de difícil cicatrização. A TVP em crianças está sendo melhor estudada nos últimos anos. Até então, seu diagnóstico e tratamento eram baseados em experiências individuais, pequenas séries de casos ou extrapolados das recomendações para adultos. Realizamos a presente revisão para melhor compreensão da epidemiologia, fisiopatologia, etiologia, diagnóstico, tratamento desta doença / Abstract: The study of deep vein thrombosis (DVT) in children and adolescents assesses the important impact of this disease on the quality of life of this population considering its long life expectancy and morbidity associated to venous thromboembolism. Within the years, the pos-thrombotic syndrome and recurrence can cause sequelae including chronic lower limb pain, edema and even hard cicatrization ulcer. Recently, DVT in children has been studied more appropriately. Previously, its diagnosis and treatment were based on individual experience, some serial cases or comparisons with recommendations to the adult treatments. This present study has been presented to better comprehend the epidemiology, physiopathology, etiology, diagnosis, treatment and prophylaxis of the deep vein thrombosis / Doutor

A system for vessel characterization aimed at detecting deep vein thrombosis (DVT) in the lower limbs has been developed and evaluated using ultrasound image processing, location and force sensors measurements, blood flow information and a protocol based on the current clinical standard, compression ultrasound. The goal is to provide an objective and repeatable system to measure DVT in a rapid and standardized manner, as this has been suggested in the literature as an approach to improve overall detection of the disease. The system uses a spatial Kalman filter-based algorithm with an elliptical model in the measurement equation to detect vessel contours in transverse ultrasound images and estimate ellipse parameters, and temporal constant velocity Kalman filters for tracking vessel location in real-time. The vessel characterization also comprises building a 3-D vessel model and performing compression and blood flow assessments to calculate measures that indicate the possibility of DVT in a vessel. A user interface designed for assessing a vessel for DVT was also developed. The system and components were implemented and tested in simulations, laboratory settings, and clinical settings. Contour detection results are good, with mean and rms errors ranging from 1.47-3.64 and 3.69-9.67 pixels, respectively, in simulated and patient images, and parameter estimation errors of 5%. Experiments showed errors of 3-5 pixels for the tracking approaches. The measures for DVT were evaluated, independently and integrated in the system. The complete system was evaluated, with sensitivity of 67-100% and specificity of 50-89.5%. System learnability and memorability were evaluated in a separate user study, with good results. Contributions include a segmentation approach using a full parameter ellipse model in an extended Kalman filter, incorporating multiple measurements, an alternate sampling method for faster parameter convergence and application-specific initialization, and a tracking approach that includes a sub-sampled sum of absolutes similarity calculation and a method to detect vessel bifurcations using flow data. Further contributions include an integrated system for DVT detection that can combine ultrasound B-mode, colour flow and elastography images for vessel characterization, a system interface design focusing on usability that was evaluated with medical professionals, and system evaluations through multiple patient studies. / Applied Science, Faculty of / Electrical and Computer Engineering, Department of / Graduate

I assessed the accuracy of two clinical prediction rules, the d-dimer blood test and point of care ultrasound for diagnosing lower limb deep vein thrombosis. Emergency physicians were trained in ultrasound and prospectively scanned emergency department patients with suspected deep vein thrombosis. Accuracy of the Wells and AMUSE rules and the ultrasound result was compared to radiology-performed ultrasound and a 90-day clinical outcome. Univariate and multivariate analyses were performed assessing which factors were associated with the outcome. The sensitivity and specificity of the Wells score for the clinical outcome was 85.7% and 68.5%; the AMUSE score 85.7% and 54.4%. Ultrasound had a sensitivity of 91.7% and specificity of 91.7% for radiology-diagnosed thrombus and 78.6% and 95.0% for clinical outcome. The odds ratio of a positive outcome with a positive ultrasound was 65.1. After receiving the ultrasound training program, emergency physicians were unable to demonstrate sufficient accuracy to replace current diagnostic strategies.

This master thesis describes a journaling system for compression ultrasonography and a clinical assessment system for deep vein thrombosis (DVT). We evaluate Support Vector Machines (SVM) models with linear- and radial basis function-kernels for predicting deep vein thrombosis, and for facilitating creation of new clinical DVT assessment. Data from 159 patients where analysed, with our dataset, Wells Score with a high clinical probability have an accuracy of 58%, sensitivity 60% and specificity of 57% these figured should be compared to those of our base models accuracy of 81%, sensitivity 66% and specificity 84%. A 23 percentage point increase in accuracy.The diagnostic odds ratio went from 2.12 to 11.26. However a larger dataset is required to report anything conclusive. As our system is both a journaling and prediction system, every patient examined helps the accuracy of the assessment. / I denna rapport beskrivs ett journalsystem samt ett system för klinisk bedömning av djupvenstromboser.Vår modell baserar sig på en stödvektormaskin (eng. Support Vector Machine) med linjär och radial basfunktion för att fastställa förekomsten av djupa ventromboser samt att hjälpa till i skapandet av nya modeller för bedömning. 159 patientjournaler användes för att fastställa att Wells Score har en klinisk precision på 58%, 60% sensitivitet och specificitet på 57% somkan jämföras med våran modell som har en precision på 81%, 66% sensitivitet och specificitet på 84%. En 23 procentenheters ökning i precision.Den diagnostiska oddskvoten gick från 2.12 till 11.26. Det behövs dock en större datamängd för att rapportera något avgörande. Då vårt system både är för journalskapande och klinisk bedömning så kommer varje undersökt patient att bidra till högre precision i modellen.

Patients with inflammatory bowel disease (IBD) are known to have an increased propensity for thromboembolic events. Like any patient with a high risk of event recurrence, most of these patients can be managed successfully with long-term warfarin therapy. We present the case of a 66-year-old woman with Crohn's disease who, despite careful attention to the management of her international normalized ratio, developed a new deep vein thrombosis and required inferior vena cava filter placement in addition to ongoing warfarin therapy to prevent recurrent pulmonary emboli. This report serves as a reminder to physicians to have a low threshold for diagnosing thromboembolic events in patients with IBD, even if they are presumed to be adequately anticoagulated. Known and theoretical contributing factors to this increased clotting tendency are also reviewed.

Background: Recent studies have suggested that patients with idiopathic pulmonary fibrosis (IPF) may have a higher risk of venous thromboembolism (VTE) compared to general population even though the results were inconsistent. Objective: To investigate the risk of VTE among patients with IPF. Methods: Comprehensive literature review using MEDLINE and EMBASE database were performed to identify studies that compared the risk of VTE among patients with IPF to general population. Effect estimates from each study were combined together using random effect model, generic inverse variance method of DerSimonian and Laird. Results: Out of 510 retrieved articles, 5 studies met the inclusion criteria and were included in the meta-analysis. A significant risk of VTE in patients with IPF was observed with the pooled risk ratio of 2.11 (95% confidence interval, 1.28-3.48). The heterogeneity was moderate with I2 of 64%. Conclusion: An approximately 2-fold increased risk of VTE among patients with IPF was observed in this meta-analysis.

Kidney and inferior vena cava (IVC) abnormalities with extensive deep vein thrombosis (DVT) is a very rare cause of DVT and has a diverse clinical presentation. Computed tomography (CT) angiography is the gold standard for diagnosis and treatment including thrombectomy, thrombolysis and systemic anticoagulation. We present a rare case of active young healthy male admitted with acute onset of right lower extremity pain and swelling who was found to have extensive DVT on doppler ultrasound. CT abdomen showed extensive clot burden involving right common femoral vein extending into internal and external iliac veins associated with IVC hypoplasia and hypoplastic left kidney. Patient underwent urgent thrombectomy, catheter directed thrombolysis and was discharged home in stable condition on oral anticoagulation.

Femoral artery pseudoaneurysm (FAP) is a common complication associated with left heart cardiac catheterization. FAP is a pulsatile encapsulated mass usually formed three to seven days after removal of the arterial sheath post cardiac catheterization. Usually, FAP is asymptomatic. Groin pain and swelling are the most common complaints in symptomatic patients. It can be associated with multiple different complications including rupture, bleeding, and vascular compression leading to venous thrombosis, limb ischemia, and neuropathy. Deep vein thrombosis (DVT) resulting from FAP is an unusual complication with very few cases reported in the literature. We present a case of right-sided DVT secondary to the compression of femoral vein resulting in venous outflow obstruction due to iatrogenic FAP post cardiac catheterization that was successfully managed conservatively.

<p>The effect of direction thrombin inhibition on acute deep vein thrombosis (DVT) stability has not been defined and could contribute to pulmonary embolism (PE) risk. Direct thrombin inhibitors (DTIs) effectively inhibit free and clot-bound thrombin, which could potentiate thrombus instability through disruption of platelet, fibrin, and FXIIIa stabilizing mechanisms. This could manifest as increased thrombus embolization. A clinically relevant mouse model of DVT stability could further our understanding of venous thrombosis pathophysiology and define the effect of direct thrombin inhibition on PE. We hypothesized that acute DTI administration would decrease acute DVT stability and potentially increase PE risk. Platelets were labeled <em>in vivo</em>, femoral vein thrombosis was induced using FeCl₃, and lepirudin (8U/g) was administered <em>after</em> clot formation. Using intravital videomicroscopy (IVM), real time embolization was quantified as a measurement of thrombus stability. Thrombus stability increased in the control group and decreased in the lepirudin-treated group over two hours. The decrease in α₂-antiplasmin (α₂-AP) content within lepirudin-treated thrombi, compared to control thrombi, could possibly contribute to the observed decrease in thrombus stability. Continued growth and embolization established the dynamic nature of formed thrombi. In both groups, emboli were detected in the pulmonary artery circulation. Therefore, we successfully developed a mouse model of venous thrombus stability, which imitated the clinical progression of DVT to PE. DTI administration in the acute DVT setting could decrease thrombus stability, demonstrated through increased embolization and PE. This model could be useful in examining the effect of other antithrombotics and risk factors settings on DVT stability.</p> / Master of Science (MSc)

La sévérité potentielle de la thrombose veineuse superficielle (TVS) des membres inférieurs a récemment été documentée par des études réalisées en soins secondaires et tertiaires. Son épidémiologie reste cependant inconnue en soins primaires. Le premier objectif de ce travail était de mesurer la prévalence de la TVS en soins primaires, ainsi que le taux d'évènements thromboemboliques concomitants au moment du diagnostic. Pour y répondre, un réseau de recherche collaborative entre médecins généralistes et médecins vasculaires de la région stéphanoise a été mis en place. Une étude transversale descriptive a été réalisée au sein de ce réseau pendant un an. La prévalence annuelle de la TVS a été mesurée à 0,64 pour mille habitants. Au moment du diagnostic, 24,6% des TVS étaient associées à une thrombose veineuse profonde symptomatique et 4,7% à une embolie pulmonaire symptomatique. Une seconde étude a recherché une variation saisonnière de la fréquence de la TVS en analysant les données individuelles de trois études aux designs différents ; l'étude STENOX, l'étude POST et l'étude STEPH. Une variation significative n'a été retrouvée que dans l'étude POST, et les peak-to-low ratios étaient inférieurs à 1,2 dans les trois études. Ainsi, si une variation existe, celle-ci parait être de faible envergure, sans conséquence sur la pratique et la recherche / The potential severity of superficial vein thrombosis (SVT) of the lower limbs has recently been shown by studies perfomed in secondary and tertiary care. The epidemiology of SVT remains unknown in primary care. The first objective of this study was to measure the prevalence of SVT in primary care, and the rate of concomitant thromboembolic events at diagnosis. A collaborative research network between general practitioners and vascular physicians from Saint-Etienne has been set up. A cross-sectional study has been conducted within this network during one year. The annual prevalence of SVT was measured to 0.64 per thousand inhabitants. At diagnosis, 24.6% of SVT were associated with symptomatic deep vein thrombosis and 4.7% with symptomatic pulmonary embolism. A second study was looking for a seasonal variation of SVT frequency by analyzing individual data from three studies with different designs; the STENOX study, the POST study and the STEPH study. A significant variation was found only in the POST study, and peak-to-low ratios were below 1.2 in the three studies. Thus, if other more powerful and exhaustive studies could find a seasonal variation, that variation would probably be of low magnitude and without clinical significance