Dissertations / Theses: 'Venous thrombosis'

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Brown, John Gordon. "A study of deep venous thrombosis." Thesis, Queen's University Belfast, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303015.

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Payne, Holly. "Novel insights into the mechanisms of venous thrombosis." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8172/.

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Venous thrombosis is a major health concern, with an annual incidence of ~1 per 1000 adults (Cushman 2007). This includes deep vein thrombosis (DVT) and pulmonary embolism (PE), the fatal consequence of a clot detaching and moving to the lungs, together these diseases are termed venous thromboembolism (VTE). Current treatment options for VTE are often associated with serious side effects and bleeding complications, highlighting the need for more effective prophylaxis. This study therefore aimed to identify new targets to treat DVT, which would not have the associated negative side effects. This study shows the platelet receptor CLEC-2 (C-type lectin receptor 2) plays an important role in DVT, probably through interaction with podoplanin in the IVC wall, and that lack of CLEC-2 is protective in this disease. We show other immune cells may also play a role in DVT, and demonstrate that mast cell deficiency is protective in vivo. Furthermore, we suggest that the mast cell constituent responsible for the prothrombotic phenotype is likely to be histamine. Preliminary data also suggests that T-cells may have a protective role in DVT, and that thrombin may be important for the release of neutrophil extracellular traps (NETs) from neutrophils inside a growing thrombus.

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Lindmarker, Per. "Treatment of deep vein thrombosis and risk of recurrent venous thromboembolism /." Stockholm, 1998. http://diss.kib.ki.se/1998/91-628-3211-5/.

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Robins, Richard. "The role of vascular Gas6 in the pathophysiology of Venous Thrombosis." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114250.

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Gas6 is a vitamin K-dependent, secreted protein that amplifies platelet aggregation and secretion in response to platelet agonists. Gas6-/- mice are protected from experimentally induced lethal venous and arterial thromboembolism. This protection has been attributed to defective aggregation in platelets from Gas6-/- mice. However, this platelet phenotype was only observed when platelets were challenged by one agonist, ADP, and only at a concentration of 5.0 µM. This subtle platelet abnormality resulting in a rather dramatic clinical phenotype raises the possibility that Gas6 from a source other than platelets contributes to thrombus formation. We hypothesize that Gas6 derived from the vasculature plays a role in venous thrombus formation. Gas6-/- mice are protected against venous thrombosis induced by 0.37 M FeCl3 in the inferior vena cava (IVC). Bone marrow transplantation experiments generating mice with selective ablations of Gas6 from either the hematopoietic or vascular compartments demonstrate an approximately equal contribution by Gas6 from both compartments to thrombus formation. Platelet depletion in wild type or Gas6-/- mice followed by reconstitution with platelets from either WT or Gas6-/- mice confirm that Gas6 from compartments other than the platelet contribute to thrombosis development. Furthermore, Gas6-/- mice are hyporesponsive to FeCl3 mediated tissue factor induction in venous endothelium, as observed by immunofluorescence micoscopy and further validated by a functional assay. In addition, in vitro, Gas6-/- endothelial cells are hyporesponsive to thrombin mediated tissue factor mRNA induction. Taken together, these results suggest that vascular derived Gas6 contributes to thrombus formation in vivo and can partially be explained by the ability of Gas6 to promote endothelial tissue factor induction. We also begin to explore the involvement of the FOX family transcription factor FoxO1 as a downstream mediator of Gas6 induced expression of VCAM-1 during endothelial activation. These findings support the notion that vascular Gas6 may play a pathophysiologic role in venous thromboembolism
Gas6 est une protéine vitamine-K dépendante, sécrétée qui contribue à l'agrégation des plaquettes. Les souris déficientes en Gas6 (Gas6-/-) sont protégées contre les thromboses artérielles et veineuses. La résistance à la thromboses des souris déficientes en Gas6 était attribuée à une réponse plaquettaire défectueuse. Cependant, la phénotype plaquettaire était observée uniquement avec le traitement des plaquettes avec une concentration faible de l'ADP (5.0µM). Cette observation indique la possibilité d'une contribution de Gas6 d'une source distincte des plaquettes. Nous faisons l'hypothèse que Gas6 dérivé d'une source vasculaire contribue à la formation d'une thrombus. Les souris Gas6-/- sont protégées contre la formation des thromboses dans la veine cave inférieure induite par 0.37 M FeCl3. En utilisant des greffes de moelle osseuse, nous avons généré des souris avec les déficits de Gas6 soit dans le compartiment vasculaire ou hématopoïétique. La formation des thromboses dans les souris chimériques était intermédiaire entre les deux groupes contrôles. L'épuisement des plaquettes dans les souris WT, suivi de la reconstitution avec des plaquettes Gas6-/- a confirmé les résultats obtenus par les greffes de moelle osseuse. En outre, l'induction du facteur tissulaire était atténuée dans les cellules vasculaires des souris Gas6-/-. Additionellement, in vitro, les cellules endothéliales étaient aussi hypo réactives en ce qui concerne l'induction du facteur tissulaire. Nos résultats suggèrent que Gas6 dérivé d'une source vasculaire contribue à la formation in vivo d'une thrombose, en partie dû a l'induction du facteur tissulaire. Nous avons commencé à examiner l'hypothèse à savoir si la protéine FoxO1 est impliquée dans l'induction de VCAM-1 parmi les cascades de signalisation de Gas6. Donc, en guise de conclusion nos résultats soutiennent l'idée que Gas6 vasculaire peut jouer un rôle physiopathologique dans la thrombose veineuse.

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Dai, Guohao 1970. "Computational and biological studies of mechanical prophylaxis against deep venous thrombosis." Thesis, Massachusetts Institute of Technology, 2001. http://hdl.handle.net/1721.1/28236.

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Thesis (Ph. D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 2001.
Includes bibliographical references (p. 137-151).
Deep vein thrombosis (DVT) of the lower extremity and induced pulmonary embolism are common complications resulting from prolonged periods of bed-rest or immobilization of the limbs. One of the most effective methods of prophylaxis against DVT is external pneumatic compression (EPC). In spite of its wide acceptance as an effective means of prophylaxis, its mechanism remains poorly understood and optimal compression conditions have not been defined. Understanding the biological consequences of EPC is an important goal for optimizing the performance of compression device and providing guidance for clinical use. In the first part of this thesis, a computational model of the leg was developed to simulate hemodynamic conditions under EPC and the influence of different modes of compression were analyzed and compared. Then, a new in vitro cell culture system was developed that can be used to examine the effect of hemodynamic conditions during EPC on endothelial cell (EC) function. The biologic response was assessed through changes in cell morphology and the expression of various pro-thrombotic and anti-thrombotic factors related to EC.
(cont.) The results show that intermittent flow associated with EPC up-regulates EC fibrinolytic potential and vasomotor function. Using DNA microarray technology, the data of thrombo-regulatory factors indicates that EC gene expression shifts toward anti-thrombotic vs. pro-thrombotic under EPC. Finally, Nitric Oxide (NO), an important regulator of vasomotor and platelet functions was studied in detail under various cycles of EPC. The results show that NO production and eNOS mRNA respond differentially to modes of EPC. Further exploration using the system can potentially reveal the optimum combination of forces to better regulate thromboresistant effects desired for DVT prophylaxis.
by Guohao Dai.
Ph.D.

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Wilson, Stanley Darrin. "An investigation of lower limb venous function, whole blood coagulation and deep venous thrombosis following proximal femoral fracture." Thesis, Queen's University Belfast, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268218.

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Horner, Daniel. "Isolated distal deep vein thrombosis in symptomatic ambulatory patients : a prospective data analysis and therapeutic feasibility study." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/isolated-distal-deep-vein-thrombosis-in-symptomatic-ambulatory-patients-a-prospective-data-analysis-and-therapeutic-feasibility-study(02979c49-ec26-4099-b0f8-3da2acbf0672).html.

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Isolated distal deep vein thrombosis (IDDVT) is a condition recently suggested to be a different entity to that of proximal disease. There is currently little evidence defining the clinical importance of detection and treatment. International guidelines vary regarding management advice.An observational cohort study, prospective service evaluation and pilot randomised controlled trial were performed within a United Kingdom ambulatory thrombosis service. This project aimed to describe the burden of disease and explore three poorly researched aspects of IDDVT assessment and management: whole-leg compression ultrasound (CUS) performed by non-physicians within an ambulatory framework as a principal diagnostic modality; clinical presentation data and risk profile in comparison to that of proximal disease; the feasibility of further interventional randomised research and the risk/benefit profile of therapeutic anticoagulation.Within this ambulatory cohort, IDDVT accounted for 49.7% of acute thrombosis and differed significantly to proximal disease regarding provocation and symptomatology at clinical presentation. A negative whole-leg CUS excluded deep vein thrombosis with an adverse event rate (diagnosis of symptomatic venous thromboembolism during the 3 month follow up period) of 0.47% (95% CI 0.08 to 2.62). Future interventional research was proved feasible within an ambulatory setting.The randomised controlled trial conducted within this project is the largest to date comparing therapeutic anticoagulation against conservative strategy for the management of acute IDDVT. Patients allocated to therapeutic anticoagulation had significantly less overall propagation of thrombus (Absolute risk reduction [ARR] 25.7%, 95% Confidence interval 5.9 to 44.3 p<0.01), less short-term symptomatic progression (ARR 16.7%, 95% CI 2.6 to 32.1 p=0.05) and a result trending towards significance for reduction in serious thromboembolic complications (ARR 11.4%, 95% CI -1.5 to 26.7 p=0.11).IDDVT is a condition of equal prevalence to proximal venous thrombosis, which varies significantly regarding risk profile and clinical presentation. Using a single whole leg CUS reported by a non-physician within an emergency department pathway is associated with a low adverse event rate. This contemporary data also suggests that therapeutic anticoagulation is beneficial for reduction of short-term complications in IDDVT. The risk of false positive diagnosis and excess anticoagulation remains.This data can inform and direct future design of adequately powered randomised studies, in order to attempt external validation of these findings.

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Pazzini, Carla. "Preparação e caracterização de nanoparticulas com heparina e sua avaliação em modelo animal de trombose venosa." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310166.

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Orientadores: Joyce Maria Annichino-Bizacchi, Nelci Fenalti Hoher
Dissertação (mestrado) - Universidade Estadual de Campinas. Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-15T09:49:31Z (GMT). No. of bitstreams: 1 Pazzini_Carla_M.pdf: 2143259 bytes, checksum: b3ff6eb2527b691a4021526983ef2aeb (MD5) Previous issue date: 2010
Resumo: A heparina é um anticoagulante amplamente empregado no tratamento e profilaxia da trombose venosa profunda (TVP). Algumas limitações do seu uso são o custo e a via de administração, endovenosa ou subcutânea, às vezes em doses repetidas em 24 horas. Assim, o desenvolvimento de um produto que possa ser administrado por via subcutânea em um menor número de aplicações ou por via oral, torna-se um importante desafio, e de grande aplicabilidade clínica. A utilização de um sistema de liberação sustentada de fármacos pode vir ao encontro desse objetivo, pois permite que o agente seja protegido e liberado gradativamente. Este projeto consistiu na preparação e caracterização de nanopartículas biodegradáveis de poli (e-caprolactona) (PCL) como carreador de heparina de baixo peso molecular, e avaliação de sua atividade anticoagulante e antitrombótica in vivo. As nanopartículas foram preparadas pelo método de dupla emulsão a/o/a e evaporação de solvente. A caracterização das nanopartículas foi realizada por microscopia eletrônica de varredura (MEV), observando-se nanopartículas esféricas e homogêneas. O diâmetro médio das nanopartículas foi de 269 ± 36 nm e o potencial zeta foi de -1,20 ± 1,93 mV, indicando que as mesmas apresentam carga negativa. A eficiência de encapsulação, analisada pelo método Azure II, foi de 80 ± 2,3%. A liberação da heparina in vitro, avaliada pelo método de Azure II, no período de 24 horas foi de 4 ± 1,8%. Após a adição da esterase houve um aumento para 10 ± 1,9% na liberação de heparina, provavelmente pela aceleração da degradação das partículas pela enzima. A liberação in vivo da heparina encapsulada, após aplicação subcutânea em ratos, foi avaliada pela atividade anti-Xa plasmática através do método colorimétrico, e os resultados foram comparados aos obtidos com heparina livre. A dose de heparina encapsulada teve que ser 5 vezes maior que a dose de heparina livre. A heparina encapsulada em nanopartículas apresentou uma liberação sustentada por até 12 horas, por um período significativamente mais prolongado (P<0,01), mas com menor atividade anti-Xa. Esses dados sugerem que as nanopartículas podem permitir que a heparina seja liberada de uma forma mais gradual, e mesmo em dose mais elevada, não parece estar associada a um risco de atividade acima da faixa terapêutica. Quando se comparou a atividade anti-Xa obtida pela injeção subcutânea de nanopartículas com heparina em doses diversas, 800 UI/Kg e 1000 UI/Kg, ficou demonstrado que o efeito e o tempo de ação dependem da dose aplicada. Para avaliação da ação antitrombótica foi padronizado o modelo de TVP por estase em ratos. As doses de nanopartículas empregadas para a avaliação da ação antitrombótica foram calculadas pela atividade anti-Xa semelhante à obtida com a heparina livre, de 0,3 a 0,7 UI/mL. A heparina livre ou encapsulada em nanopartículas foi aplicada em uma única dose, por via subcutânea. Os resultados mostraram que houve diminuição significativa do trombo formado com a utilização de heparina livre, em comparação ao grupo controle (P=0,004). Praticamente não houve a formação de trombose venosa em nenhum dos ratos que receberam a heparina encapsulada em nanopartículas, com uma diferença significativa tanto em relação ao grupo controle (P<0,001) como ao grupo com heparina livre (P<0,001). Em resumo, o método de dupla emulsão a/o/a mostrou-se um método eficiente para o encapsulamento de heparina, proporcionando a obtenção de nanopartículas esféricas e com alta eficiência de encapsulação. Pelos estudos in vivo, a heparina encapsulada não liofilizada mostrou uma liberação sustentada, por um período superior ao obtido com a heparina livre, e com excelente ação antitrombótica. Caso esses resultados se confirmem através da continuidade deste estudo, a utilização de heparina encapsulada em nanopartículas na prática clínica poderá ser uma realidade com grandes vantagens para o paciente.
Abstract: Heparin is an anticoagulant widely used in the treatment and prophylaxis of deep vein thrombosis (DVT). Some limitations of its use is the cost and route of administration, intravenous or subcutaneous, sometimes in repeated doses in 24 hours. Thus, the development of a product that can be administered subcutaneously in a smaller number of applications or orally becomes a major challenge, with interesting clinical applications. The use of a system for sustained release of drugs can come to meeting that goal, because it allows the agent to be protected and released gradually. This project consisted of the preparation and characterization of biodegradable nanoparticles of poly (e-caprolactone) (PCL) as a carrier of heparin of low molecular weight, and its evaluation of anticoagulant and antithrombotic activity in vivo. The nanoparticles were prepared by the method of double emulsion w/o/w and evaporation of solvent. The characterization of nanoparticles was performed by scanning electron microscopy (SEM), which showed homogeneous spherical nanoparticles. The average diameter of nanoparticles was 269±36 nm and zeta potential was -1.20±1.93 mV, indicating negative charge. The encapsulation efficiency, assayed by Azure II, was 80±2.3%. The release of heparin in vitro, at the 24-hour period was 4±1.8%. After the addition of esterase the release of heparin was increased to 10±1.9%, probably by accelerating the degradation of particles by the enzyme. The in vivo release of encapsulated heparin after subcutaneous administration in rats, was assessed by anti-Xa plasma activity and the results were compared with free heparin. The dose of heparin encapsulated had to be 5 times the dose of heparin free. Heparin-encapsulated nanoparticles showed a sustained release for up to 12 hours for a period significantly longer (P<0.01), but with lower anti-Xa activity. These data suggest that nanoparticles may allow heparin to be released in a more gradual, but with lower activity. When comparing the anti-Xa activity obtained by subcutaneous injection of nanoparticles with different doses of heparin, 800 IU/kg and 1000 IU/kg, demonstrated that the effect and duration of action depends on the dose applied. To evaluate the antithrombotic action of nanoparticles with heparin a model of DVT by stasis in rats was used. The doses of nanoparticles used for the evaluation of antithrombotic action were calculated by anti-Xa activity similar to that obtained with free heparin, 0.3 to 0.7 IU/mL. Heparin free or encapsulated in nanoparticles was applied in a single dose subcutaneously. The results showed a significant decrease of thrombus formed with the use of free heparin, compared with the control group (P=0.004). There were virtually no formation of venous thrombosis in any of the rats that received heparin encapsulated in nanoparticles, with a significant difference both in the control group (P<0.001) and the group with free heparin (P<0.001). In summary, the method of double emulsion w/o/w proved an efficient method for the encapsulation of heparin, providing spherical homogeneous nanoparticles with high encapsulation efficiency. For in vivo studies, heparin encapsulated showed a sustained release for a period greater than that of free heparin, and with excellent antithrombotic action. If these results are confirmed by the continuity of this study, the use of heparin encapsulated in nanoparticles in clinical practice can be of great benefits for the patient.
Mestrado
Medicina Experimental
Mestre em Fisiopatologia Médica

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Andia, Kohnenkampf Marcelo. "Venous thrombosis : formation, evolution and resolution imaging using non-invasive MRI techniques." Thesis, King's College London (University of London), 2012. https://kclpure.kcl.ac.uk/portal/en/theses/venous-thrombosis-formation-evolution-and-resolution-imaging-using-noninvasive-mri-techniques(99e7c5ac-77eb-4d0e-aad7-c90aa4202c79).html.

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Deep venous thrombosis (DVT) remains a major health problem. Although thrombolytic therapies are effective in recanalising the veins, restoring blood flow, preventing pulmonary embolism and post-thrombotic complications, there is still no consensus on the selection criteria for this invasive treatment. Experimental data suggest that thrombus rich in fibrin has better response to thrombolysis than red cell rich (acute phase) or collagen rich (chronic) thrombus. Thus, there is a need for a diagnostic technique that provides better information on the stage of thrombus organization in-vivo and allows identification of thrombus suitable for thrombolysis. Current imaging modalities for the diagnosis of DVT do not provide information on the biological stage of thrombus organization. Contrast venography is still considered the gold standard for the diagnosis of DVT, even though thrombi are not clearly visualized and they are indirectly detected due to alterations in blood flow. The aim of this thesis was to develop and validate new imaging methodology for the better evaluation of DVT using Magnetic Resonance Imaging (MRI). The first aim was to investigate the potential of non-contrast enhanced MRI sequences including T1 mapping, T2* mapping, Magnetization Transfer Contrast (MTC), and Apparent Diffusion Coefficients (ADC) maps for the detection of thrombus in a murine model of deep venous thrombosis. The second aim was to investigate the merit of a fibrin and macrophage specific MR contrast agent for the detection of DVT. Both fibrin and macrophages play a major role in thrombus organization. The third aim was to investigate the merits of the fibrin binding contrast agent for the guidance of thrombolysis. We also developed two new non-contrast enhanced venous spin labelling approaches in order to obtain venograms without the need of a contrast agent and thereby to improve non-invasive DVT diagnosis using MRI. In conclusion, this thesis proposes a new imaging methodology for the accurate staging of thrombus organization and the successfully detection of thrombus amenable for thrombolysis in a murine model of DVT. The translation of this technique into the clinic should have great potential to change clinical evaluation and treatment of patients with DVT.

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Vossen, Carolina Y. "Genetic risk factors for venous thrombosis : key players or minor risk modifiers ? /." [S.l. : s.n], 2005. http://catalogue.bnf.fr/ark:/12148/cb402235083.

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Svensson, Peter J. "Resistance to activated protein c a novel risk factor for venous thrombosis /." Lund : Dept. for Coagulation Disorders, Malmö University Hospital, Lund University, 1997. http://catalog.hathitrust.org/api/volumes/oclc/68945075.html.

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Lapidus, Lasse. "Thromboembolism following orthopaedic surgery : outcome and diagnostic procedures after prophylaxis in lower limb injuries /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-111-1/.

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Duffett, Lisa. "Management of Superficial Venous Thrombosis: A Systematic Review of Literature and Survey of Canadian Physicians." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37105.

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Superficial venous thrombosis (SVT) is a common inflammatory and thrombotic pathology occurring within a superficial vein. SVT can result in distressing symptoms of redness and pain in the affected area and exposes patients to a risk of developing deep vein thrombosis (DVT) and pulmonary embolism (PE). Various therapeutic options are available to patients including anti-inflammatories, anti-coagulation and surgical procedures, however which of these therapies is the best first line treatment remains unknown. Several randomized controlled trials have been conducted addressing this question, yet methodological and design flaws have limited the translation of their results into a change of clinical practice. The following thesis consists of a multi-step process of reviewing the evidence to date followed by a process of engaging with clinician stakeholders with the goal of designing a randomized control trial that would provide a meaningful answer to patients and their clinicians. In the first step of this process, a systematic review of the literature was performed, including a meta-analysis to estimate pooled risk of developing symptomatic venous thromboembolic (VTE) complications in patients with isolated SVT following various treatments. These results were then presented to expert Canadian clinicians in a series of surveys using a Delphi process to determine the clinical trial design that would have the greatest impact on changing clinical practice. An additional survey of expert clinicians was conducted to determine current practice variation in the diagnosis, management, and follow up of patients with SVT, in order to design a clinical trial that best reflected current standard Canadian clinical practice. Our systematic review identified 15 articles and including 5775 patients. Quality and assessment of risk of bias was moderate for most included studies. The findings of our meta-analysis identified that Fondaparinux, at prophylactic dose, to had the lowest event rate of 2.0 events per 100 patient years of follow-up (95% CI 0.4 to 4.7, I2=33%) for the primary outcome of deep vein thrombosis (DVT) or pulmonary embolism (PE) during follow-up. Pooled event rates ranged from 8.6-16.6 events per 100 patient-years across other treatment categories, including placebo/observation only, with an event rate of 10.5 events per 100-patient years (95% CI 3.0 to 22.0). Heterogeneity was moderate to high for most pooled estimates, limiting the interpretation of these findings. Our survey of practice variation among expert Canadian clinicians revealed wide practice variation in in diagnosis and therapeutic management including sub-groups (e.g. cancer). There was agreement that clinical equipoise exists for the optimal treatment of SVT (77% of respondents), supporting the need for further research. Two rounds of surveys were performed using Delphi process methods, resulting in consensus for the design of a future randomized control trial (RCT). The agreed on design was for a randomized control trial comparing a direct oral anticoagulant (DOAC) such as Rivaroxaban, to Non-Steroidal Anti-Inflammatories (NSAIDs), using a non-inferiority RCT design with a non-inferiority margin of 3%. Future direction of this research will be to continue stakeholder engagement by engaging patients in the clinical trial design, followed by development of a pilot RCT protocol and application for peer-reviewed funding.

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Beauchamp, Nicholas James. "Molecular genetic basis of inherited thrombophilia." Thesis, University of Sheffield, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287349.

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Sevestre-Pietri, Marie-Antoinette. "Réactualisation de modèles épidémiologiques et application à la maladie thromboembolique veineuse." Grenoble, 2010. http://www.theses.fr/2010GRENS042.

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La maladie thrombo-embolique veineuse est une entité hétérogène avec des formes cliniques de présentation et de pronostic variables. Compte tenu de l'évolution démographique de la population, de la grande diffusion d'outils diagnostiques fiables et de l'impact de la thromboprophylaxie, il nous a paru nécessaire de réactualiser les connaissances sur ce sujet. Trois études épidémiologiques ont permis les analyses de ce travail. Pour les sujets âgés en soins de suite lors d'une étude de type coupe transversale avec évaluation de type avant/après, nous avons montré que les patients âgés avaient des facteurs spécifiques comme l'immobilisation prolongée, le grand âge (plus de 80 ans), la présence d'escarres et la dépendance estimée par l'indice IADL. Le bénéfice de la prévention est hautement probable dans cette population car nous avons trouvé un taux de thromboses asymptomatiques de 15% avec une réduction d'un tiers après une action de sensibilisation à la thromboprophylaxie. Par contre, le bénéfice de la compression doit être évalué chez la personne âgée. L'étude Optimev a étudié les facteurs de risque, les méthodes diagnostiques et le pronostic des différentes formes cliniques de MTEV (de la thrombose superficielle à l'embolie pulmonaire). Pendant 15 mois, des médecins vasculaires hospitaliers et libéraux ont saisi grâce à un cahier d'observation électronique, les facteurs de risque, les examens complémentaires et le traitement mis en place auprès de 8256 patients avec suspicion clinique de MTEV. Un suivi téléphonique à 3 mois, 6 mois, un an et trois ans a été effectué. Le suivi des TVP distales (n=787), proximales (n=598), TVP avec EP (n=371), EP sans TVP (n=130) et des contrôles (n=2404) montre que la mortalité à 3 mois des EP sans TVP est proche de celle des contrôles (4%) alors que celle des patients EP avec TVP est de 13%. Les TVP distales sont la forme la plus fréquente de MTE ( 56,8% vs 43,2% pour les proximales), leurs facteurs de risque sont plus souvent transitoires et elles récidivent tout autant que les proximales, même si leur mortalité est plus faible. Parmi les TVP distales, les thromboses musculaires sont comparables aux thromboses des troncs jambiers. Le diagnostic d'élimination de TVP par écho-Doppler a été validé pour les patients externes et pour la première fois chez des patients hospitalisés. Optimev a également permis de valider une règle clinique simple de probabilité de TVP du membre supérieur. Ce travail permet de mieux comprendre la signification des formes cliniques diagnostiquées actuellement et leur pronostic à court terme. Les perspectives pour cette étude portent sur les éléments pronostiques de ces différentes formes cliniques mais aussi la relation avec les pathologies ischémiques artérielles. Summary
Venous thrombo-embolism is a heterogenous disease. Clinical presentation, prognosis vary greatly among patients and requires standardization. Using 3 epidemiological studies, we have analyzed, risk factors and diagnostic tools that are described in venous thromboembolism (VTE) and compared clinical forms. The following models have been tested: - two epidemiologic cross sectional studies of elderly patients describing risk factors and asymptomatic thrombosis detected by systematic ultrasound. Elderly patients have specific risk factors like prolonged immobilisation, dependance, age over 79 years, ulcers. The benefit of prevention is established and enhanced by a 15% rate of asymptomatic venous thromboses. Despite this, the benefit of antithrombotic compression is not proven and deserves further work. - The Optimev study, a national survey about 8256 clinical suspicions of VTE, describes risk factors and clinical description and long term follow-up for positive and negative patients. Calf vein thrombosis is the clinical form mostly prevalent (n=787). Actual analysis of clinical forms like isolated pulmonary embolism (n=130) show that mortality is close to controls in patients with PE without DVT ( 4%) whereas it is close to 13% in patients with PE with DVT; thus, the presence of DVT when diagnosis PE is of clinical importance. Deep vein thromboses and muscular thromboses are compared; they share the same risk factors and 3 month's mortality, clinical presentation is different; deep vein thromboses are more associated with swelling but less painful than muscular ones. 3 month follow-up shows that a negative ultrasound rules out VTE safely as well for in and out-patients. A clinical prediction rule for upper extremity DVT is also presented. Future works such as : 3 years follow-up, superficial venous thromboses, post thrombotic syndrome and qualification of past episodes of VTE are warranted Mots clés

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Opatrny, Lucie. "A case-control study examining the association between travel and deep venous thrombosis /." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82303.

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Background. This thesis explores the link between travel and deep venous thrombosis (DVT). While it is biologically plausible that prolonged travel is an independent risk factor for venous thromboembolic disease (VTE), epidemiological data to date are conflicting.
Aim. To determine whether there is a independent association between travel and DVT.
Methods. This was a multi-center case control study. Consecutive patients presenting to the vascular laboratory with clinically suspected DVT were eligible to participate. Cases were patients with confirmed DVT; controls were patients who had DVT ruled out. Travel history and clinical characteristics were determined though standardized interviewer-administered questionnaire. Genetic testing of Factor V Leiden and Prothrombin gene mutations were also performed. SAS was used to perform unconditional multivariate logistic regression analysis.
Results. There were 359 cases and 359 controls. The crude and adjusted odds ratios (OR) for travel and DVT were 1.15 (95%CI: 0.78, 1.69) and 1.51 (95%CI: 0.91, 2.50) respectively. Travel of >=12 hours' duration had a higher OR estimate (2.82, 95%CI: 0.52, 15.24) than shorter travel durations (OR = 1.32, 95%CI: 0.63, 2.76), although this did not reach statistical significance. Analyzing plane and car travel separately showed that plane travel of >=12 hours duration had a crude and adjusted OR of 8.22 (95%CI: 1.02, 66.05) and 7.10 (95% CI: 0.70, 72.35). No such association was found with long durations of car travel.
Interpretation. Plane travel appears to be a mild independent risk factor for DVT overall, although the adjusted OR does not achieve conventional levels of statistical significance. Plane travel durations of 12 hours or longer had the highest estimate of risk. This was not found to be true of car travel. These findings may have future implications regarding the use of thromboprophylaxis in travelers.

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Aronen, Hannu J. "Imaging methods in the diagnosis of suspected deep venous thrombosis of the leg." Hki : Societas scientiarum Fennica, 1989. http://catalog.hathitrust.org/api/volumes/oclc/57854420.html.

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18

Flores-Nascimento, Mariane Cristina 1979. "Pesquisa de microparticulas plaquetarias circulantes em individuos com trombose venosa profunda, sindrome do anticorpo antifosfolipideo ou fator V de Leiden." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310164.

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Orientador: Joyce Maria Annicchi-Bizzacchi
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: A Trombose Venosa Profunda (TVP) é uma doença multicausal, mas muitos fatores de risco ainda não estão definidos. Micropartículas (MPs) são pequenas vesículas liberadas da membrana celular durante ativação e apoptose. MPs podem ser um reflexo da dinâmica entre repouso, ativação e morte celular e podem contribuir com a gravidade da doença pois são procoagulantes e pro-inflamatórias. Parece haver associação entre elevado número de MPs e risco de complicações tromboembólicas, que podem ter um papel na patogênese destas doenças. Neste estudo avaliamos e caracterizamos as MPs em pacientes com TPV de membro inferior, [ao diagnóstico (5M/4H, idade média=41,1 anos), após 6 meses de tratamento (7M/3H, idade média=32,9 anos), associada à Síndrome do Anticorpo Antifosfolípide (7M/3H, idade média=33,8 anos)], em portadores assintomáticos do Fator V de Leiden (FVL) (7M, idade média=34 anos), e comparando-as a controles pareados por sexo, idade e etnia. As MPs foram isoladas de sangue periférico citratado, por centrifugação diferencial. A quantificação e caracterização foram feitas por citometria de fluxo usando os anticorpos: CD235, CD61, CD45, CD31, CD14, CD45, anti-TF e Anexina V. A atividade procoagulante plasmática foi investigada pela dosagem do fragmento 1+2 de protrombina (F1+2). A atividade procoagulante das MPs foi analisada pela dosagem de F1+2, de Dímero-D (DD2) e pelo teste de geração de trombina (TGT) em pool de indivíduos saudáveis em presença de MPs, corrigidas ou não por número na amostra (10.000 MPs). A análise estatística empregou os testes Wilcoxon ou U de Mann-Whitney, a=0.05. O número de MPs não estave diminuído em nenhum dos grupos estudados. A porcentagem de MPs estava estatisticamente aumentada nos pacientes com SAF/TVP em relação a seus controles (P=0,007). Observou-se um aumento significativo das MPs plaquetárias nos pacientes com SAF/TVP (P=0,01) e diminuição das MPs endoteliais naqueles com TVP ao diagnóstico (P=0,03), quando comparados aos seus controles. Os pacientes com SAF/TVP apresentaram diminuição significativa do F1+2 plasmático, tanto em relação aos seus controles (P=0,008) como ao CTR total (P=0,002). O F1+2 gerado pelas MPs estava significativamente diminuído em indivíduos com FVL em relação ao CTR total (0,009), e em pacientes com SAF/TVP em relação aos seus controles (P=0,001), e ao CTR total (P=0,008). O DD2 em pool de plasma, independente do número de MPs, estava significativamente aumentado na comparação entre TVP ao diagnóstico e seus controles (P=0,008) e ao CTR total (P=0,0001). O DD2 em pool com número corrigido de MPs apresentava-se aumentado significativamente nos pacientes com TVP ao diagnóstico quando comparados aos seus controles (P=0,008). Os valores do TGT com número corrigido de MPs estavam estatisticamente diminuídos em pacientes com TVP após 6 meses (P=0,01), em comparação ao CTR total. Nossos resultados demonstraram que o número de MPs está alterado em pacientes com TVP, e talvez possam ter um papel, particularmente após o evento trombótico ou em presença de anticorpos antifosfolípides. As MPs demonstraram atividade procoagulante, principalmente ao diagnóstico de TVP, podendo contribuir ou agravar o quadro clínico do paciente
Abstract: Deep Venous Thrombosis (DVT) is a multicausal disease, but many risk factors are not well defined. Microparticles (MPs) are small blebs released from cellular surfaces during activation and apoptosis. MPs may be the consequence of the dynamics between rest, activation and cellular death and can contribute to the seriousness of the illness and are therefore procoagulant and pro-inflammatory. There seems to be an association between high numbers of MPs and risk of thromboembolic complications and these may have a role in pathogenesis of these illnesses. In this study, we evaluated and characterized the MPs in patients with DVT of inferior limbs, [at diagnosis (5M/4H, medium age= 41.1 years), after 6 months of treatment (7M/3H, medium age= 32.9 years), and associated to Antibody Antiphospholipid Syndrome (7M/3H, medium age= 33.8 years)], and asymptomatic carriers of Factor V Leiden (FVL) (7M, medium age 34= years), matched to health controls by sex, age and ethnic origin. The MPs were isolated from citrated peripheral blood, by differential centrifugation. The quantification and characterization were performed by flow cytometry using the antibodies: CD235, CD61, CD45, CD31, CD14, CD45, anti-TF and Annexin V. The plasmatic procoagulantic activity was investigated by prothrombin fragment 1+2 (F1+2) dosage. The MPs procoagulant activities were analyzed by F1+2 dosage, D-dímer (DD2) and Thrombin Generation Test (TGT) in a pool of healthy individuals in the presence of MPs, corrected or not for number in the sample (10.000 MPs). Statistical analysiswas performed by Wilcoxon or the Mann-Whitney tests, a=0.05. The MPs number were not lower in any of the studied groups. The MPs percentage was statistically increased in the SAF/DVT patients compared to their matched controls (P=0.007). A significant increase in the platelet-derived MPs in SAF/DVT patients (P=0.01) and a reduction in the endothelial-derived MPs at diagnosis were observed (P=.03), when compared to their matched controls. The SAF/TVP patients show a significant reduction in plasmatic F1+2, when compared to their matched controls (P=0.008) and to the total CTR (P=0.002). The F1+2 generated by MPs were significantly lower in FVL carriers compared to the total CTR (0.009), and in SAF/DVT patients compared to their controls (P=0.001), and to the total CTR (P=0.008). The DD2 in the pool of plasma, independently of the number MPs, was significantly higher in DVT at diagnosis when compared to their matched controls (P=0.008) and the total CTR (P=0.0001). The DD2 in the pool with corrected MPs number was significantly higher in DVT at diagnosis patients when compared to their matched controls (P=0,008). The values of TGT in corrected MPs number were statistically lower in patients with DVT after 6 months (P=0.01), in comparison to the total CTR. Our results demonstrated that the number of MPs is modified in patients with DVT, and may play a role, particularly after the thrombotic event or in association with antiphospholipid antibodies. The MPs demonstrated procoagulant activity, especially at DVT diagnosis, and were able to contribute or to aggravate the patient¿s clinical situation
Mestrado
Biologia Estrutural, Celular, Molecular e do Desenvolvimento
Mestre em Fisiopatologia Médica

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Rao, Deepa Prema. "The role of growth arrest-specific 6 in venous thromboembolism /." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112349.

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Background. Growth-arrest specific 6 (gas6) is a novel vitamin-K dependent protein whose role in venous thromboembolism was recently characterized in murine models. Gas6 is suggested to be a prothrombotic protein capable of mediating thrombus stability. However, the association between gas6 and venous thromboembolism has yet to be elucidated in humans. The present work aims to delineate the existence of such an association in humans and propose a mechanism by which gas6 expression is related to venous thromboembolic disease.
Methods. To analyze the association between gas6 and venous thromboembolism, a highly specific ELISA method was used to measure plasma gas6 levels in 306 patients with a history of deep-vein thrombosis (DVT) and 89 control volunteers. Medication history, comorbid conditions and DVT characteristics were documented for the purposes of statistical analyses. Median gas6 levels were compared between the subgroups, and prevalence rate ratios were calculated. Human umbilical vein endothelial cells were used to measure the effect of gas6 treatment on the expression of various mediators of coagulation. Murine thrombosis models were developed to serve as in vivo models for thrombosis.
Results. The median levels of gas6 were 28.21 ng/ml in patients compared to 26.15 ng/ml in controls (p=0.01). After adjustment for age, sex, comorbidity and medications, DVT patients had a PRR of 2.5 (95% CI 1.36 to 4.61, p=0.003) compared with controls. Within the DVT subgroup, median gas6 levels were significantly higher in those with cancer-associated (vs. unprovoked or secondary) DVT (p<0.001) and in those with more extensive DVT (p=0.037), while levels were significantly lower in those taking warfarin (vs. no warfarin) (p=0.03). Preliminary results with endothelial cell cultures are inconclusive with regards to the effect of gas6 on endothelium derived mediators of coagulation.
Conclusions. Elevated plasma gas6 is associated with venous thromboembolism. The etiology of the clot influences detected levels of gas6, with the highest levels seen in cancer-patients. Furthermore, increasing clot burden correlates with elevated levels of gas6. A mechanistic explanation for how gas6 modulates this association is in its preliminary stages, and is worth pursuing.

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20

Holmström, Margareta. "Clinical aspects on treatment of deep venous thrombosis with a low molecular weight heparin /." Stockholm, 1998. http://diss.kib.ki.se/1998/91-628-2989-0/.

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21

Dörffler-Melly, Janine. "Experimental, clinical, and meta-analytical studies of antithrombotic therapies in venous and arterial thrombosis." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2001. http://dare.uva.nl/document/59215.

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22

Al, Rawahi Bader. "Efficacy and Safety of Pharmacological Thromboprophylactic Agents for the Prevention of Venous Thromboembolism after Major Abdominal Surgery." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36050.

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Statement of the problem: The type and duration of pharmacological thromboprophylaxis post major abdominal surgery remains controversial. Methods of investigation: A systematic review and pooled analysis of literature was performed to assess the risk benefit ratio of the different pharmacological thromboprophylaxis agents compared to placebo or no thromboprophylaxis post major abdominal surgery. A survey of the clinical practice among both general surgeons and thrombosis expert was conducted. Results: The systematic review demonstrated that all five pharmacological thromboprophylaxis regimens were associated with similar rates of overall VTE. The 95% CI of the different estimates overlapped indicating no statistically significant difference between any of the pharmacological interventions and placebo. While all the surgeons and thrombosis experts recommended thromboprophylaxis post major abdominal surgery, over 70% of them recommended it during hospitalization only. Conclusion: Pharmacological thromboprophylaxis was not associated with a significant benefit in reducing the rate of overall VTE events post major abdominal surgery. There is an agreement between general surgeons and thrombosis experts in using LMWH for thromboprophylaxis post major abdominal surgery. However, there is still equipoise around the use of pharmacological thromboprophylaxis post discharge.

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Castellucci, Lana Antoinette. "Evaluating Risk of Delayed Major Bleeding in Critically Ill Trauma Patients." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/33442.

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Background: Up to 40% of trauma patients die during the first 24 hours after injury due to massive hemorrhage. In patients who survive this critical time period, no information is available on rates of delayed major bleeding or factors associated with delayed major bleeding. Methods: A retrospective chart review of 150 critically ill adult trauma patients was used to determine the incidence of delayed major bleeding events. Cox proportional hazards multivariate analysis was performed to assess for risk factors associated with delayed major bleeding events. The anticipated rate of delayed major bleeding events was 10%. Results: The incidence of delayed major bleeding in this cohort of critically ill trauma patients was 44%. Predictors that were statistically significantly associated with delayed major bleeding included: male gender, pre-injury use of the antiplatelet agents aspirin and/or clopidogrel, presence of intracranial bleeding, higher injury severity scores, requirement of massive transfusion, and low pH values. Use of anticoagulant prophylaxis was not associated with delayed major bleeding. Conclusion: The rate of delayed major bleeding was higher than estimated. Larger retrospective and prospective cohorts are needed to confirm these findings.

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Smith, Sarah Faith. "Influences on the incidence of clinical deep vein thrombosis and pulmonary embolism in a prospectively collated population of 21,000 neurosurgical inpatients." Thesis, The University of Sydney, 2001. http://hdl.handle.net/2123/818.

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Records of all neurosurgical inpatients admitted to Royal North Shore Hospital since 1976 have been prospectively kept in a relational database. Demographic details, diagnoses, operations and complications have been entered continuously since 1982 by the author of this study. Complications are monitored at monthly review meetings attended by medical staff. The recurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE) at these meetings, despite continual improvements in patient care, prompted this study. It aims to use the database to study changes in the incidence of DVT and PE over the previous twenty years; to find what database variables predict these complications; and whether use of mechanical and pharmacological agents has had an impact on DVT and PE rate. Univariate analysis of the incidence of DVT and PE by age, sex, length of stay (LOS), admission month, diagnosis, operation and surgeon over time was run. Any significant variables were then analysed by multivariate logistic regression. The DVT rate was low by world standards, but rose from 0.6% in 1979-83 to 1.2% in 1984-88, then rose exponentially to 3.60% in 1994-98 with a significantly increasing trend over the twenty years (c2 MH =114.20, with IDF, P<0.001). PE rate doubled significantly over the twenty years from 0.6% to 1.2% (c2 MH =17.94 with 1DF, P<0.001). Age, LOS, diagnosis, operation and surgeon were significant predictors of DVT and PE. After adjustment for LOS, time period and age, vascular surgery was found to be the strongest predictor of DVT (OR=2.82, 95% CI: 2.08-3.82, c2 =43.91, P<0.01). Vascular diagnosis was the strongest diagnosis predictor. No effect of sex or month of admission was shown. After adjustment for LOS, time period and age, spinal fusion was the strongest predictor of PE (OR=4.04, 95% CI: 1.81-9.03). Anterior communicating artery aneurysm was the diagnosis most highly associated with PE. The rise in DVT rate may be due to increased complexity of surgical and nursing management, and some screening of patients with the introduction of duplex scanning. The doubling of PE rate is unexplained. The risk of brain or spinal cord haemorrhage makes prophylactic anticoagulation a difficult choice. This study reveals groupings which can be used to determine appropriate prophylaxis. Use of mechanical and pharmaceutical agents is not recorded consistently in the database, but it is known approximately when they were introduced. No impact on the rate of DVT and PE can be demonstrated by these agents. More vigilant and widespread use of mechanical prophylaxis might be just as effective in controlling DVT and PE.

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Smith, Sarah Faith. "Influences on the incidence of clinical deep vein thrombosis and pulmonary embolism in a prospectively collated population of 21,000 neurosurgical inpatients." University of Sydney. Public Health and Community Medicine, 2001. http://hdl.handle.net/2123/818.

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Records of all neurosurgical inpatients admitted to Royal North Shore Hospital since 1976 have been prospectively kept in a relational database. Demographic details, diagnoses, operations and complications have been entered continuously since 1982 by the author of this study. Complications are monitored at monthly review meetings attended by medical staff. The recurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE) at these meetings, despite continual improvements in patient care, prompted this study. It aims to use the database to study changes in the incidence of DVT and PE over the previous twenty years; to find what database variables predict these complications; and whether use of mechanical and pharmacological agents has had an impact on DVT and PE rate. Univariate analysis of the incidence of DVT and PE by age, sex, length of stay (LOS), admission month, diagnosis, operation and surgeon over time was run. Any significant variables were then analysed by multivariate logistic regression. The DVT rate was low by world standards, but rose from 0.6% in 1979-83 to 1.2% in 1984-88, then rose exponentially to 3.60% in 1994-98 with a significantly increasing trend over the twenty years (c2 MH =114.20, with IDF, P<0.001). PE rate doubled significantly over the twenty years from 0.6% to 1.2% (c2 MH =17.94 with 1DF, P<0.001). Age, LOS, diagnosis, operation and surgeon were significant predictors of DVT and PE. After adjustment for LOS, time period and age, vascular surgery was found to be the strongest predictor of DVT (OR=2.82, 95% CI: 2.08-3.82, c2 =43.91, P<0.01). Vascular diagnosis was the strongest diagnosis predictor. No effect of sex or month of admission was shown. After adjustment for LOS, time period and age, spinal fusion was the strongest predictor of PE (OR=4.04, 95% CI: 1.81-9.03). Anterior communicating artery aneurysm was the diagnosis most highly associated with PE. The rise in DVT rate may be due to increased complexity of surgical and nursing management, and some screening of patients with the introduction of duplex scanning. The doubling of PE rate is unexplained. The risk of brain or spinal cord haemorrhage makes prophylactic anticoagulation a difficult choice. This study reveals groupings which can be used to determine appropriate prophylaxis. Use of mechanical and pharmaceutical agents is not recorded consistently in the database, but it is known approximately when they were introduced. No impact on the rate of DVT and PE can be demonstrated by these agents. More vigilant and widespread use of mechanical prophylaxis might be just as effective in controlling DVT and PE.

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26

van, Rooijen Marianne. "Effects of combined oral contraceptives on hemostasis and biochemical risk indicators for venous thromboembolism and atherothrombosis /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-089-3/.

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27

Amini, Nekoo Ali. "Molecular analysis of human tissue factor pathway inhibitor (TFPI) gene in relation to venous thrombosis." Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427717.

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Cheung, Katharine Lana. "Chronic Kidney Disease and the Risk of Venous Thromboembolism." ScholarWorks @ UVM, 2018. https://scholarworks.uvm.edu/graddis/879.

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Chronic kidney disease (CKD) affects more than 30 million adults in the U.S. and is strongly associated with cardiovascular events and mortality. Venous thromboembolism (VTE) is the third leading vascular disease, affects up to 900,000 Americans each year and contributes to as many as 100,000 deaths annually. The relationship of CKD and VTE has been described in patients receiving dialysis, kidney transplants recipients and in nephrotic syndrome, however, data supporting the association of VTE in mild to moderate CKD is conflicted. The overall goal of this research was to study the association of CKD and VTE and to understand the mechanisms of this association. To accomplish this goal we studied participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, a nationally representative cohort of 30,239 blacks and whites in the U.S.. The first chapter provides a review of the state-of-the science on CKD and VTE and potential mechanisms for this association. We focus on factor VIII as a potential mediator of VTE risk in CKD by reviewing the biochemistry and epidemiology linking factor VIII and CKD. In Chapter 2, we use a cohort study design and a competing risk analysis to determine the risk of VTE with albuminuria (ACR) and with various equations for estimated glomerular filtration rate (eGFR). There was no association of ACR and VTE and the risk of VTE was similar among eGFR equations. Compared to a normal eGFR (>90 ml/min/1.73m2), eGFR < 45 ml/min/1.73m2 was associated with a two-fold risk of VTE. The association of eGFR and unprovoked VTE was similar to the association with provoked VTE. The population attributable fraction of CKD (eGFR<60 ml/min/1.73m2) was modest at 5%. In Chapter 3, we utilize a case-cohort study to determine if biomarkers of inflammation (C-reactive protein) and procoagulation (Factor VIII and D-dimer) attenuate the risk of VTE in CKD. These biomarkers were higher in lower kidney function and were also strongly associated with VTE. Adjustment for factor VIII fully attenuated the risk of VTE in CKD, thus factor VIII is a potential mediator of the association of CKD and VTE. We assessed whether lifestyle factors and medications mitigate the risk of VTE in those with and without CKD. Exercise frequency and use of statins were associated with reduced risk of VTE in the presence and absence of CKD, but normal BMI was associated with reduced VTE risk only in those without CKD. We conclude that CKD is a risk factor for VTE, and findings shed light on the mechanisms of this association. Interventions that might lower VTE risk in CKD patients include exercise and statin therapy, but not weight loss. Factor VIII is a potential mediator of VTE in CKD and deserves further study. We suggest several avenues for future research to explore the relationship of Factor VIII and CKD.

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Ikesaka, Rick. "The Risk of Upper Extremity Deep Vein Thrombosis and Primary Thromboprophylaxis with Low Dose Rivaroxaban in Oncology Patients with Central Venous Catheters." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/41954.

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Venous thromboembolism (VTE) is a common disorder which causes significant morbidity and mortality. Upper extremity deep vein thrombosis(UEDVT) is a relatively understudied subtype of VTE which is commonly associated with central venous catheters, cancer, and thrombophilia. The goal of this project was to better characterize the risk of UEDVT and to design and execute a pilot study that will demonstrate the efficacy of a strategy preventing the occurrence of VTE in a high-risk population for UEDVT. This M.Sc project, was conducted in three parts. Chapter 1 of the thesis outlines a systematic review of the literature which assessed the risk of VTE in UEDVT patients by search for and including data from studies with patients with prospectively enrolled symptomatic UEDVT. Chapter 2 describes the development and final protocol of the TRIM-Line pilot study, a randomized open-label study comparing 90 days of rivaroxaban 10mg po daily against the current standard of care (observation) in patients with active cancer and central venous catheters, two known risk factors for VTE. Finally in Chapter 3 the TRIM-Line study was executed as a pilot trial involving The Ottawa Hospital and the Juravinski Cancer Centre located in Hamilton. The study was conducted from March 2019 until February 2020. 105 patients underwent randomization at the two Canadian centres. The study met its prespecified feasibility endpoint average enrolment rate of 7.5 per month (95% CI:4.56, 10.44) at the coordinating Ottawa Hospital site and 2.0 per month (95% CI:0.87, 3.13) for the Juravinski Cancer Centre site. The randomized controlled trial met its enrollment targets and demonstrated that a full scale randomized controlled trial on the topic of prevention of cancer associated venous thromboembolism is feasible.

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Alessio, Aline Morandi. "Associação dos polimorfismos nos genes dos receptores alfa e beta do estrogeno em pacientes com trombose venosa profunda." [s.n.], 2005. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311375.

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Orientador: Nelci Fenalti Hoehr, Joyce M. Anichino-Baizzacchi
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: o estrógeno atua na hemostasia promovendo efeitos pró e antitrombóticos, sua ação ocorre através de sua ligação a receptores nucleares específicos, denominados receptores 'alfa' e 'beta' do estrógeno (RE). A presença de polimorfismos nos genes que codificam o RE poderia modular a resposta do estrógeno, assim como a transcrição de genes e conseqüentemente a expressão. Existem fatores de risco adquiridos para a trombose venosa profunda (TVP) que estão associados a alterações do nível de estrógeno como: gravidez, puerpério, uso de anticoncepcional oral (ACO) e a terapia de reposição hormonal. Os objetivos deste estudo foram de associar polimorfismos nos genes dos RE 'alfa' e 'beta' em controles e mulheres e homens com TVP e avaliar a influência deles na atividade da proteína C (PC), proteína S (PS), antitrombina e concentração de fibrinogênio. Nas mulheres sob o uso de ACO, o genótipo AA do polimorfismo G1730A e, nas mulheres grávidas, os genótipos AA e GA do polimorfismo G1082A, ambos no gene do RE-~, podem ter um efeito protetor para o risco de TVP. Porém, o genótipo GG do polimorfismo G1730A tem uma influência no aumento da atividade da PS nas mulheres do grupo controle total e nas mulheres sob o uso de ACO; e os genótipos AA e AG do polimorfismo A351G no gene do RE-'alfa' , e o genótipo GG do polimorfismo G1082A tem um efeito no aumento da concentração de fibrinogênio nas mulheres grávidas. Contudo, a mutação G20210A no gene da protrombina, o fator V de Leiden e os polimorfismos do RE- foram fatores preditores de trombose venosa. Apesar da miscigenação brasileira, a PC apresentou diminuída em mulheres AITo-descendente. Nossos resultados sugerem que polimorfismos no gene dos RE-'beta' têm uma influência maior no risco para TVP. A contribuição deste trabalho é de grande importância, pois nenhum estudo associou o risco de TVP com os polimorfismos dos RE-'beta'
Abstract: Estrogen acts in haemostasis promoting pro and antithrombotic effects. Its action occurs through linking the specific nuclear receptors called 'alfa' and 'beta' estrogen receptor (ER). Polymorphisms in the genes that codify the ER a and ~could modulate estrogen response, as well as gene transcription and expression. There are acquired risk factors for deep venous thrombosis (DVT) that can alter the estrogen levels. These factors are oral contraceptives (OC), hormonal replacement therapy, pregnancy, and puerperium. The objectives of this study were to associate the polymorphisms in the genes of the a and ~ER in controls, women and rnen with DVT, and to evaluate the influence of these polyrnorphisms in protein C, protein S (PS), in antithrombin activity and fibrinogen concentration. Women under OC use with the AA genotype ofthe G1730A polyrnorphism, and pregnant women with the AA and GA genotypes of the G1082A polymorphism, both in the ER-~ gene, could have a protective effect for DVT risk. However, GG genotype of the G1730A polymorphisrn has an influence in the increase of the PS activity in women of the total control group and women under OC use; and the AA and AG genotypes of the A351G polymorphism in the ER-a gene, and the GG genotype of the G1O82A polymorphism have an effect in the increase of the fibrinogen leveI in pregnant women. However, the G20210A rnutation in the prothrombin gene, the Leiden V factor and the polymorphisms in the ER-'alfa' gene were predictor factors of venous thrombosis. Despite Brazilian miscegenation, PC activity was lower in Afro-descendent women. Our results suggest that the polymorphisrns in the ER-'beta' gene have a higher influence for DVT risk. The contribution of this study is of great importance, as no study has associated DVT risk with the ER polymorphisms yet
Mestrado
Patologia Clinica
Mestre em Ciências Médicas

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Flores-Nascimento, Mariane Cristina 1979. "Identificação de proteínas diferencialmente expressas em pacientes com trombose venosa profunda." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310154.

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Orientador: Joyce Maria Annichino-Bizzacchi
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A trombose venosa profunda (TVP) é uma doença multifactorial, e possui uma alta taxa de morbi-mortalidade devido a complicações como embolia pulmonar e a síndrome póstrombótica, e cerca de 25 % dos pacientes apresentarão recorrência em 5 anos. A identificação de novos fatores envolvidos na fisiopatologia da TVP pode ser convertida em implicações de grande importância no manejo destes pacientes, prevenção de recorrência e no desenvolvimento de novas terapias. O interesse em avaliar as plaquetas e as amostras de plasma se deve ao fato de que as funções plaquetárias não estão completamente compreendidas, e aparentemente o papel das plaquetas poderia ir além do seu envolvimento na hemostasia. Como o plasma potencialmente fornece uma janela para a observação do indivíduo como um todo, a análise proteômica tanto das plaquetas como do plasma poderia implementar o nosso conhecimento acerca da fisiopatologia da TVP. OBJETIVO: Neste estudo foram analisados os perfis proteicos de plaquetas e amostras de plasma de três pacientes com TVP, que foram comparados com os resultados obtidos a partir de amostras de 1 irmão e 1 vizinho para cada paciente, a fim de minimizar as interferências genéticas e ambientais. Estes pacientes apresentaram episódios espontâneos e recorrentes de TVP proximal e mencionaram um histórico familiar de distúrbios da coagulação. MÉTODOS: as plaquetas necessitaram ser lavadas e lisadas, e as amostras de plasmas tiveram a albumina depletada antes de as proteínas serem alquiladas, reduzidas, precipitadas com acetona e hidrolisadas com tripsina. Os peptídeos das plaquetas e das amostras de plasma foram fracionados por cromatografia de fase reversa e troca catiônica, respectivamente. Depois disto, os peptídeos plaquetários foram direcionados ao espectrômetro de massas LTQOrbitrap e a busca das proteínas foi realizadas através do Sorcerer/Sequest. Os peptídeos plasmáticos foram encaminhados ao espectrômetro de massas ESI Q-TOF Premier e as proteínas foram analisadas pelo Mascot. RESULTADOS: Cinco proteínas estiveram presentes apenas nas plaquetas dos pacientes, estando ausentes em todos os controles: a proteína ligante da Apolipoproteína A1, a sub-unidade ?1 do Coatômero, a Desidrogenase 11-17-? do Estradiol, a Leucotrieno A-4 Hidrolase e a Sorbitol Desidrogenase. Além disso, verificou-se que outras proteínas estiveram diferencialmente expressas em amostras de plasma pacientes e controles: a protease C4-A, o inibidor C1 da Inter-?-Tripsina, o inibidor H1 de cadeia pesada, a proteína Amilóide Sérica A, a glicoproteína ?-2-HS, a isoforma 2 da inter- ?-tripsina, a apolipoproteína A-IV e o inibidor de cadeia pesada H4. CONCLUSÕES: A avaliação de plaquetas e amostras de plasma de pacientes com TVP espontânea permitiu a identificação de proteínas diferencialmente expressas quando comparados a irmãos e vizinhos, que podem desempenhar importantes papéis na fisiopatologia da doença por se relacionarem a processos inflamatórios, imunes e no de transporte de lipídeos
Abstract: Deep venous thrombosis (DVT) is multi-causal disease associated to a high morbimortality due to complications as pulmonary embolism and post-flebitic syndrome, and about 25 % of the patients present recurrence in 5 years. The identification of new factors involved to the physiopathology of DVT can be translated into important implications for the management of these patients, prevention of recurrence, and for the development of new therapies. We were interested about platelets and plasma because the platelets functions are not completely understood and apparently their role goes beyond a hemostatic player, and as the plasma potentially provides a window into the individual's state of health and disease, both could improve our knowledge about the DVT physiopathology. AIM: In this study we analyzed the protein profile of platelets and samples of plasma of 3 DVT patients and compared to results obtained from 1 sibling and 1 neighbor for each patient in order to minimize the genetic and environmental interferences. These patients presented spontaneous and recurrent episodes of proximal DVT and mentioned a familiar history of coagulation disorders. METHODS: the platelets needed to be washed and lysed, and the plasmas samples required albumin depletion before the proteins being alkylated, reduced, precipitated with acetone and hydrolyzed by trypsin. The peptides were fractionated by reverse phase and cation exchange liquid chromatography for platelets and plasmas samples, respectively. After that, the platelets peptides were directed to LTQ-Orbitrap mass spectrometer and the proteins search were performed by Sorcerer/Sequest. The plasma peptides went to ESI Q-TOF Premier mass spectrometer and the proteins were searched by RESULTS: We identified 5 proteins that were present on platelets from patients and absent in all the controls: Apolipoprotein A1 Binding-Protein, Coatomer (?1 sub-unit), Estradiol 11-17-? Dehydrogenase, Leukotriene A-4 Hydrolase and Sorbitol Dehydrogenase. In addition, we verified 6 proteins that were differently expressed between patients and controls: C4-A plasma protease, C1 inhibitor Inter-alpha-trypsin, inhibitor heavy chain H1, the serum amyloid A, alpha-2-HS-glycoprotein, isoform 2 of inter-alphatrypsin, apolipoprotein A-IV and the inhibitor heavy chain H4. CONCLUSIONS: The evaluation of platelets and plasma samples from patients with spontaneous DVT allows the identification of proteins that are differently expressed when compared to siblings and neighbors, which can play important roles on the physiopathology of the disease due their relation to inflammatory, immune and lipid transportation
Doutorado
Biologia Estrutural, Celular, Molecular e do Desenvolvimento
Doutor em Fisiopatologia Medica

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32

Antovic, Aleksandra. "Determinations of the overall haemostasis potential and fibrin gel permeability : method development and application in research and in clinical materials /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-932-3/.

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Karevaara, Anette. "Komplikationer hos patienter med PICC." Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-213215.

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SAMMANFATTNING Bakgrund: PICC är en central infart som används inom vården för att kunna ge kärlretande läkemedel. Komplikationer vid användning av PICC kan vara infektion, trombos, tromboflebit eller stopp i katetern. Syfte: Syftet med studien är att undersöka förekomsten av komplikationer av PICC hos onkologiska patienter samt för att se om det finns några skillnader mellan olika diagnosgrupper och behandlingar med avseende på förekomsten av djupa ventromboser (DVT) och infektioner. Syftet är också att ta reda på hur länge en PICC sitter och hur vanligt det är att en PICC felplaceras. Metod: Metoden som används är en retrospektiv, deskriptiv, kvantitativ undersökning. I studien ingår alla onkologpatienter som fått en PICC år 2009-2011 (n=677). Data samlades in med hjälp av journalgranskning. Resultat: Förekomsten av DVT var 5,6 %. Patienter som fick behandling med Capecitabin hade statistiskt signifikant mer DVT jämfört med andra behandlingar. Patienter som fick behandling med R-CHOP hade statistiskt signifikant mindre DVT jämfört med andra behandlingar. Antalet infektioner var 3 %. Stopp i katetern drabbade 1,8 % av patienterna, 17 % hade besvär med rodnad under förbandet, 12 % av alla katetrar åkte ut 4 cm eller mer och 2,5 % av katetrarna felplacerades vid inläggningen. En PICC var insatt i medelvärde 92 dagar, median 105 dagar. Slutsats: Förekomsten av komplikationer av PICC var låg hos onkologiska patienter med undantag för hudbesvär som förekom hos var sjätte patient. Behandlingar innehållande Capecitabin förefaller öka risken för DVT men fler studier behövs för att öka kunskaperna om detta. PICC är en säker venös infart vid behandling med cytostatika.
ABSTRACT Background: PICC (peripherally inserted central catheter) is a central line used in healthcare to provide vascular irritant drugs. Complications with PICC can be infection, thrombosis, thrombophlebitis or occlusion of the catheter. Aim: The aim of the study is to examine the incidence of complications of PICC in oncology patients and to see if there are any differences between diagnostic groups and treatments for the presence of deep venous thrombosis (DVT) and infection. The aim is also to find out for how long time a PICC is inserted and how common it is for a PICC misplaced. Method: The method used is a retrospective, descriptive, quantitative survey. The study includes all oncology patients who received a PICC years 2009-2011 (n=677). Data were collected through medical record review. Results: The incidence of DVT was 5,6 %. Patients treated with Capecitabin had statistically significantly more DVT compared with other treatments. Patients treated with R-CHOP had statistically significantly less DVT compared with other treatments. The incidence of infections was 3 %. Occlusion of the catheter affected 1,8 % of patients, 17 % had problems with redness under the dressing, 12 % of all catheters went out four cm or more and 2,5 % of the catheters were misplaced at insertion. A PICC was inserted in mean 92 days, median 105 days. Conclusion: The complication rate of PICC was low in oncology patients with the exception of skin problems that occurred in every sixth patient. Treatments containing Capecitabin appears to increase the risk of DVT but more studies are needed to raise awareness of this. PICC is a safe venous access for chemotherapy.

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Cardoso, Luciana Ventura. "Terapia da bota de unna na redução do edema em portadores de lesão venosa." Faculdade de Medicina de São José do Rio Preto, 2018. http://hdl.handle.net/tede/425.

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Venous insufficiency is linked to longevity; an aggravating factor worldwidely, its main complication is venous ulcer. The boot of Unna is one of the forms of compression therapy. The bioimpedanciometry investigates accurately the patient's water balance. Objective: To evaluate the lower limb edema during the day comparing the use of the Unna’s boot and the conventional dressing through bioimpedanciometry. Material and Method: Fifteen legs with active wounds were evaluated, from September 2014 to December 2016. Randomization was drawing and the statistical analysis was performed using the paired t test, considering an alpha error of 5%. Results: The female representation was 100% of the total participants, the age ranged from 50 to 76 years, a mean age was 63 years. A significant difference between volume variations between morning and afternoon was found among those who did not wear the Unna’s boot. When compared the difference of edema with and without the Unna’s boot, it was detected that without the Unna’s boot the edema volume was higher. Conclusion: Unna’s boot showed better results than conventional dressing in relation to the reduction of lower limb edema during the day in patients with chronic venous ulcer.
A insuficiência venosa está ligada à longevidade; um agravo mundial, sua principal complicação é a úlcera venosa. A bota de Unna é uma das formas de terapia de compressão. A bioimpedânciometria investiga com acurácia o balanço hídrico do paciente. Objetivo: Avaliar o edema de membro inferior no transcorrer do dia comparando o uso da bota de Unna e o curativo convencional por meio da bioimpedânciometria. Material e Método: Foram avaliadas 15 pernas com feridas ativas, teve duração de setembro 2014 a dezembro de 2016. A randomização foi por sorteio e a análise estatística foi realizada utilizando-se o teste t pareado, considerando erro alfa de 5%. Resultados: A representatividade feminina foi de 100% do total de participantes, a idade variou de 50 a 76 anos, a média da idade foi 63 anos, com desvio padrão SD= 7,5. Detectou-se uma diferença significante entre as variações de volume entre o período da manhã e da tarde entre os que não usaram a bota de Unna. Quando comparada a diferença do edema com e sem bota de Unna, detectou-se que sem o uso da bota, o volume do edema foi maior. Conclusão: A bota de Unna mostrou-se superior ao curativo convencional na redução do edema de membro inferior no transcorrer do dia, dos pacientes com úlcera venosa crônica.

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Almeida, Maria Antônia Campos. ""Fibrinogênio como marcador de trombose"." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/5/5136/tde-15092006-141829/.

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INTRODUÇÃO: Um grande número de estudos epidemiológicos têm demonstrado que o fibrinogênio é fator de risco consistente e independente para doença cardiovascular. O fibrinogênio, além de ser um determinante de trombose arterial foi considerado fator de risco de trombose venosa. Foram avaliados os níveis plasmáticos do fibrinogênio em indivíduos que apresentaram algum tipo de trombose não influenciada por reação de fase aguda ou resposta inflamatória. MÉTODOS: Neste estudo de caso-controle realizado entre julho de 2003 a abril de 2005 foram incluídos 39 pacientes, entre 25 e 65 anos, com diagnóstico objetivamente confirmado de trombose, sem antecedentes de neoplasia e colagenose. O tempo mínimo entre a evento e a coleta da amostra de sangue foi de 6 meses. O grupo controle foi constituído de doadores e funcionários voluntários do Hemocentro Regional de Juiz de Fora. A concentração plasmática de fibrinogênio e a medida da Proteína C Reativa foram realizados nos dois grupos. RESULTADOS:Os níveis médios de fibrinogênio foram significativamente maiores nos pacientes ( 316)que no grupo controle (259), p=0,0002. a média de idade foi 48,3 para os pacientes e 45,5 para o controle. A aplicação do teste qui quadrado demonstrou que não houve diferenças significativas nos grupos de pacientes e controles (30,8% e 27%, respectivamente) em relação ao tabagismo(pvalor = 0,72). A frequência de hipertensão foi significativamente maior no grupo de pacientes (28,2%) que no controle (5,4%) (p-valor=0,008). O teste t para a diferença dos níveis médios de fibrinogênio entre os grupos de trombose venosa e arterial não apresentou resultado estatisticamente significante (p-valor = 0,69). CONCLUSÃO: Com base nos dados deste estudo, os níveis de fibrinogênio estão relacionados com trombose, independente se arterial ou venosa.
INTRODUCTION: A great number of prospective epidemiologic studies have reported that fibrinogen is consistently and independently risk factor for the cardiovascular disease. The fibrinogen, a determinant of arterial thrombosis, was also considered a risk factor for the venous thrombosis. It was valued the fibrinogen plasmatic level in patients that had showed some kind of thrombosis event without influence by acute phase reactions or ongoing inflamatory responses. METHODS: In this cases-control study, fulfilled between july 2003 and april 2005, was included 39 patients, among 25 e 65 ears, with confirmed diagnosis of thrombosis and none neoplasis and collagenosis antecedent. Six months was the minimum time between event and blood sample collect. The control group was composed by blood donor and voluntary employee of the Hemocentro Regional de Juiz de Fora. The fibrinogen plasmatic concentration and the C-reactive proteins measure was made in both groups. RESULTS: The medium levels of fibrinogen were significantly higher in patients (316) than the control group (259), p=0,0002. The age average was 48,3 for the patients and 45,5 for the control. The qui-quadrado test application proved there wasnt any significatives differences in both groups, patients (30,8%) and control (27%), in the relation with smoking (p-value = 0,72). The frequency of arterial hypertension was significantly higher in patient group (28,2%) than the control group (5,4%) (p-value = 0,008). The t-test for the differences of the fibrinogen average levels between venous and arterial thrombosis didnt present any significant statistic result. CONCLUSION: Established in this research, the higher levels of fibrinogen are associated with thrombosis, independently if arterial or venous.

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36

Murchison, John Tallach. "New insights into the natural history of thrombo-embolic disease provided by imaging and disease quantification." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/8185.

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Venous thromboembolism (VTE) is a common disease with a myriad of presentation. It is often difficult to diagnosis with symptoms which are shared with many other disorders. Because of the overlap in symptomatology with other pathologies it is both commonly overlooked when present and commonly considered when absent. The threshold for investigating suspected VTE has dropped over time, in part due to a greater awareness of the disease among clinicians, but also because of the greater availability of diagnostic tests which are both accurate at positively diagnosing VTE and are patient friendly. This has resulted in a mushrooming of the number of diagnostic tests being performed for suspected VTE in radiology departments. As such radiology provides a window into the disease in a way that no other speciality can. All branches of medicine having their share of VTE patients but radiology provides a unique opportunity to study VTE patients as, no matter from which speciality they arise when the disease is suspected, they will almost inevitably end up undergoing a definitive radiological test. There is much still to learn about VTE however developments in modern imaging and computerised databases have advanced our understanding of this common disease. The window that radiology provides into VTE has contributed towards those advances.

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37

Hussain, Raza, Alay Mansurov, Kanishka Chakraborty, and Alisa Vasileva. "Absence of Infrarenal inferior vena cava Leading to Deep Venous Thrombosis and Incidental Finding of Nutcracker Syndrome." Digital Commons @ East Tennessee State University, 2020. https://dc.etsu.edu/asrf/2020/presentations/17.

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Introduction: Inferior vena cava (IVC) malformations are extremely rare. Their impact with additional risk factors has not been well studied. Here, we present a case of a young female with absent IVC. She presented with an extensive left lower extremity (LLE) deep venous thrombosis (DVT) after starting oral contraceptives. Case: A 21-year-old female with no past medical history presented with progressively worsening back pain and LLE edema. Her only medication was combined oral contraceptive (OCP) which was started 4 months ago. Physical exam was significant for blue discoloration of her LLE extending from foot to thigh. The ultrasound showed multiple thrombi within the left common and deep femoral veins, left popliteal vein and left peroneal vein. The abdominal computerized tomography revealed the absence of an infrarenal IVC with collateral azygous, hemiazygous and prominent left gonadal veins. Occlusion by the thrombi extended from the left femoral vein to the left iliac vein. Some extension was noted into the right common iliac vein. She was treated with a catheter directed tissue plasminogen activator (tPA) infusion into the left iliac vein followed by continuous heparin infusion. Hypercoagulable testing was negative. While on heparin, she developed asymptomatic gross hematuria. CT urogram showed a significant dilation of the left gonadal vein, a large vein along the left psoas muscle draining into the left renal vein, and a mild enlargement of right gonadal vein. The urine analysis was negative for bacterial infection; but it contained a numerous amount of red blood cells and protein. Once the hematuria had resolved, she was discharged on apixaban. Her OCP was discontinued. Discussion: There have been several case reports describing IVC abnormalities associated with DVT. In our case, DVT was likely provoked by usage of OCP. Current guidelines would require provoked DVTs to be treat for at least 3-12 months with anticoagulation therapy. Case reports of IVC malformations illustrated that these patients are at high risk for DVT at baseline. Hence the underlying abnormality still poses a lifetime risk. Also, with abnormal venous vasculature, gross hematuria, proteinuria and the lack of other causes, we suspect underlying Nutcracker syndrome (NS). Her pelvic abdominal pain can also be attributed to pelvic congestion syndrome, which is commonly associated with NS. Conclusion: There are several questions that arise from this case including: selecting a type of contraceptive method; safety of direct thrombin inhibitors in patients with NS; indefinite direct thrombin inhibitors in young patients. Unfortunately, due to the rarity of this condition, no set guidelines are available on how to manage these individuals.

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38

Alessio, Aline Morandi. "Avaliação das células endoteliais circulantes na trombose venosa profunda : pacientes e modelo animal." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310150.

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Orientador: Joyce Maria Anichino-Baizzacchi
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: As células endoteliais participam da hemostasia com efeitos pró e antitrombóticos, que podem ser estimulados por uma lesão endotelial. A presença de células endoteliais na circulação pode ser considerada um novo marcador de integridade vascular, como já descrito em várias patologias tais como: doenças cardiovasculares, doenças infecciosas, doenças imunes, transplantes, anemia falciforme. Os objetivos do nosso estudo foram: padronizar a identificação e quantificação das células endoteliais circulantes (CECs) e das células endoteliais progenitoras (CEPs) em um grupo de pacientes com trombose venosa profunda (TVP) ao diagnóstico (aguda, 1ª coleta) e após no mínimo 6 meses (2ª coleta), em um grupo de TVP crônica e em um grupo controle; padronizar um modelo animal de TVP induzida por lesão endotelial para avaliar as CECs e CEPs no sangue periférico e no trombo venoso. O grupo de TVP aguda foi composto por 9 pacientes [F: 7; M: 2; 45 anos (26 - 54 anos)], sendo recrutados 6 indivíduos para uma 2ª coleta [F: 5; M: 1; 47,5 anos (27 - 55 anos)], no grupo de TVP crônica foram incluídos 10 pacientes [F: 6; M: 4; 44,5 anos (28 - 56 anos)] e no grupo controle 11 voluntários [F: 9; M: 2; 29 anos (21 - 52 anos)]. A identificação das CECs e CEPs no sangue periférico foi realizada por citometria de fluxo. No modelo animal, a TVP foi induzida por lesão endotelial com uma solução de FeCl3 a 15%. Após a indução da TVP as CECs e CEPs foram avaliadas no sangue periférico nos tempos: 15 minutos, 30 minutos, 45 minutos, 1 hora, 24 horas, 48 horas e 72 horas. O trombo venoso formado na veia cava inferior (VCI) foi avaliado pela coloração de Verhoff van Gienson e a presença de CECs e CEPs por imunofluorescência. Houve uma diferença estatística no número das CECs (P=0.001, CD31+CD144+CD45dimCD133-; P<0.001, CD31+CD146+CD45dimCD133-; P=0.002, CD31+VEGFR2+CD45dimCD133-) entre os grupos estudados, com um aumento importante nos pacientes com TVP aguda. Os grupos de TVP crônica e TVP 2ª coleta mostraram um aumento significativo de CECs em relação aos controles. Não houve diferença estatística no número das CEPs (CD34+VEGFR2+CD45dimCD133-) entre os grupos estudados, porém observou-se um aumento no grupo de TVP aguda. No modelo animal, a oclusão total da VCI foi verificada entre 15 minutos e 1 hora. Após 24 horas ocorreu uma diminuição progressiva da área do trombo formado [85,4% (24h); 65,4% (48h); 51,3% (72h)], e não foram observadas CECs e CEPs no mesmo. No sangue periférico, no tempo de 48 horas houve um aumento importante de CECs e CEPs quando comparado com os outros tempos estudados (P=0.001, Sca1-VEGFR2+CD45dim; P=0.004, CD34-VEGFR2+CD45dim; P<0.001,Sca1+VEGFR2+CD45dim; P<0.001, CD34+VEGFR2+CD45dim). Os resultados observados em camundongos e humanos sugerem que as CEPs podem ser recrutadas da medula óssea para a circulação, participando do processo de reparo endotelial. O aumento de CECs na fase em que se inicia o processo de recanalização no modelo animal, sugere que apesar da lesão endotelial inicial, as mesmas somente são liberadas quando o fluxo começa a ser restabelecido. Neste estudo concluímos que as CECs podem constituir um marcador de dano vascular.
Abstract: Endothelial cells participate in hemostasia and have pro and anti -thrombotic effects which can be stimulated by an endothelial lesion. The presence of endothelial cells in circulation can be considered a novel marker of vascular integrity, as described in several pathologies, such as: cardiovascular disease, infectious disease, immune diseases, transplants, and sickle cell anemia. The aims of our study were to: standardize the identification and quantification of circulating endothelial cells (CECs) and progenitor endothelial cells (EPCs) in a group of patients with Deep Vein Thrombosis (DVT) at diagnosis (acute, 1st collection) and after a minimum of six months (2nd collection), in a group with chronic DVT and in a control group; standardize an animal model with DVT induced by endothelial lesion in order to evaluate CECs and EPCs in peripheral blood and in venous thrombosis. The group of DVT was composed of 9 patients [F: 7; M: 2; 45 years old (y.o.) (26 - 54 y.o.)], of which six individuals were recruited for the 2nd collection [F: 5; M: 1; 47.5 y.o. (27 - 55 y.o.)]; in the chronic DVT group 10 patients were included [F: 6; M: 4; 44.5 y.o. (28 - 56 y.o.)]; and in the control group 11 volunteers were included [F: 9; M: 2; 29 y.o. (21 - 52 y.o.)]. The identification of CECs and EPCs in peripheral blood was carried out by flow cytometry. DVT was induced in the animal model by endothelial lesion using a FeCl3 solution at 15%. After DVT induction, CECs and EPCs were evaluated in peripheral blood at: 15 minutes, 30 minutes, 45 minutes, 1 hour, 24 hours, 48 hours and 72 hours. The venous thrombus formed in the inferior cava vein (ICV) was evaluated using Verhoff van Gienson stain and the presence of CECs and EPCs was evaluated using immunofluorescence. There was a statistical difference in the number of CECs (P=0.001, CD31+CD144+CD45dimCD133-; P<0.001, CD31+CD146+CD45dimCD133-; P=0.002, CD31+VEGFR2+CD45dimCD133-) between the groups studied, with a significant increase in acute DVT patients. The chronic DVT and 2nd collection DVT groups demonstrated a significant increase in CECs in relation to the controls. There was no statistical difference in the number of EPCs (CD34+VEGFR2+CD45dimCD133-) among the groups studied, however an increase in the acute DVT group was observed. In the animal model, total ICV occlusion was observed between 15 minutes and 1 hour. After 24 hours a progressive decrease in the area of the formed thrombus occurred [85.4% (24h); 65.4% (48h); 51.3% (72h)], and no CECs or CEPs were observed. After 48hours, there was a significant increase in CECs and EPCs in peripheral blood when compared to other periods studied (P=0.001, Sca1-VEGFR2+ CD45dim; P=0.004, CD34-VEGFR2+CD45dim; P<0.001, Sca1+VEGFR2+CD45dim; P<0.001, CD34+VEGFR2+CD45dim). The results observed in mice and human beings suggest that EPCs can be recruited to circulation from the bone marrow, participating in a process of endothelial repair. The increase of CECs during the phase when the re-channeling process begins in the animal model, suggests that despite the initial endothelial lesion, CECs are liberated when the flow is reestablished. In the present study we concluded that CECs can represent a vascular damage marker.
Doutorado
Medicina Experimental
Doutor em Ciências

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39

Bassora, Fernanda Dutra Santiago 1982. "Avaliação da expressão gênica de marcadores inflamatórios em células mononucleares de pacientes com trombose venosa profunda." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310152.

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Orientador: Joyce Maria Annichino Bizzacchi
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A trombose venosa é definida como a oclusão de um vaso do sistema venoso. Três fatores básicos para a formação de um trombo no interior dos vasos são: alteração do fluxo sangüíneo, da parede vascular e/ou dos elementos sangüíneos. A trombose venosa e a embolia pulmonar, que ocorre como uma complicação subseqüente representa uma causa importante de morbidade e mortalidade em pacientes hospitalizados. A freqüência da trombose venosa foi estimada em aproximadamente 1/1000 na população em geral. Na maior parte dos casos existe uma tendência para trombose determinada pela presença de um fator causal herdado ou adquirida, ou pela interação desses fatores, bem como por variações genéticas que determinam alterações nos níveis das proteínas pró-coagulantes e anticoagulantes. Dados da literatura têm sugerido a associação de mecanismos inflamatórios com a fisiopatologia da trombose venosa profunda (TVP). Os monócitos, estimulados por citocinas ou endotoxinas, expressam fator tecidual, o maior indutor da coagulação sangüínea, e que também tem a função de sinalização para a mobilidade celular e vascular. Os leucócitos apresentam receptores capazes de ligar e ativar o fator X da coagulação, servindo como via alternativa para a formação de trombina. As plaquetas podem aderir ao endotélio intacto e através da liberação de mediadores e citocinas como interleucina (IL)-1 e Fator de necrose tumoral-a (TNF-a), induzindo a expressão de moléculas de adesão e fator tecidual pela célula endotelial. Com base nestes dados e considerando que a migração leucocitária é um dos principais eventos que caracterizam o processo inflamatório, justificamos a escolha de células mononucleares (monócitos e linfócitos) como células centrais do nosso estudo. Utilizando técnicas de separação de células mononucleares por centrifugação em gradiente de "Ficoll-Hypaque", extração do Ácido ribonucléico (RNA) total, hibridação em Ácido desoxiribonucléico complementar (cDNA) -Microarray, e validação usando a reação em cadeia da polimerase em tempo real quantitativo (qRT-PCR) avaliamos do perfil de expressão gênica de alguns mediadores inflamatórios nessas células e a possível relação com a trombose venosa. Neste trabalho, usando a tecnologia de Microarray encontramos 60 induzidos e 56 genes reprimidos diferencialmente expressos nos pacientes com TVP, estes genes que estavam relacionados à resposta imune, inflamação, proteólise e transcrição. Destes genes diferencialmente expressos, selecionamos nove relacionados com inflamação para validação usando a técnica de qRT-PCR. Destes, somente houve aumento de expressão do gene da caspase 4 (CASP4) nos pacientes com TVP, sendo que, esta diferença se manteve no subgrupo com TVP espontâneo. Neste mesmo subgrupo, também foi verificado o aumento da expressão no gene Elong factor 1, alpha 2(EEF1A2)
Abstract: Venous thrombosis is defined as a vessel occlusion of the venous system. Three basic factors for the formation of a thrombus inside the vessel are: changes in blood flow, vascular wall and / or blood elements. Venous thrombosis and pulmonary embolism, which occurs as a subsequent complication is a major cause of morbidity and mortality in hospitalized patients. The frequency of venous thrombosis was estimated to be approximately 1 / 1000 in the general population. In most cases there is a tendency for thrombosis determined by the presence of a causal factor inherited or acquired, or by the interaction of these factors, as well as genetic variations that determine changes in protein levels of procoagulants and anticoagulants. Literature data have suggested the association of inflammatory mechanisms in the pathophysiology of deep venous thrombosis (DVT). Monocytes, stimulated by cytokines or endotoxin, express tissue factor, the greater inducer of blood coagulation, and also have the function of signaling for cell motility and vascular. Leukocytes have receptors that can bind and activate coagulation factor X, serving as an alternative route for the formation of thrombin. Platelets can adhere to intact endothelium and through the release of mediators and cytokines such as interleukin (IL)-1 and Tumor necrosis factor-a (TNF-a), inducing expression of adhesion molecules and tissue factor by endothelial cells. Based on these data and considering that leukocyte migration is one of the main events that characterize the inflammatory process, we justify the choice of mononuclear cells (monocytes and lymphocytes) as the central cells of our study. Using techniques of separation of mononuclear cells by gradient centrifugation "Ficoll-Hypaque," extraction of total RNA, cDNA-Microarray hybridization, and validation using real time qPCR assessed the gene expression profile of some inflammatory mediators in these cells and the possible relationship with venous thrombosis. In this work using Microarray technology we found 60 genes upregulated and 56 downrelated differentially expressed in patients with DVT. Genes that were related to immune response, inflammation, proteolysis and transcription. Of these differentially expressed genes, we selected nine genes that were related with inflammation to validation using qRT- PCR technique. Just one of then, the caspase 4 (CASP4) genes was differentially increased in DVT patients, this increase kept in patients with spontaneous DVT and an increased of Elong factor 1, alpha 2 (EEF1A2) gene too
Doutorado
Ciencias Biomedicas
Doutora em Ciências Médicas

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Bayoumy, Nervana M. K. "Genetic analysis of plasma von Willebrand factor antigen levels as a risk factor for arterial and venous thrombosis." Thesis, University of Aberdeen, 2006. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU223247.

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We carried out the first genome-wide linkage analysis in British families for VWF levels. ABO and VWF loci were specifically examined. The results showed that VWF levels are highly heritable 42% ( P>0.000001) with age and C-reactive protein (CRP) the main covariates. The ABO locus was strongly associated with VWF levels ( P=2x10-18), but linkage was modest (LOD = 1.6). VWF gene marker showed no significant association or linkage with phenotype. Genome-wide linkage analysis, conditioned on age and ABO genotypes, revealed regions with potential linkage. Highlighted regions were on chromosomes 2 and 3 (LOD = 1.78 & 1.08 respectively) and two areas on chromosome 12 (LOD = 1.5 & 1.3). Inflammatory biomarkers concentrations were also investigated. Heritabilities of CRP and tumour necrosis factor-alpha (TNF-alpha) were significantly high 38% and 47% respectively, while interleukin-6 was not heritable. VWF levels showed significant genetic correlation with CRP. As ABO group has a major role in determining VWF levels, if the VWF stroke association is causal, blood groups should be associated with stroke (Mendelian Randomisation). ABO genotype frequencies in stroke patients were investigated by a case-control study (503 objectively diagnosed cases and 327 controls). Non-O groups were not significantly over-represented in stroke cases (OR 1.1, CI95 0.83--1.47). Monte Carlo method, taking into account ABO effect on VWF levels, showed no association between ABO genotypes and stroke risk. This was reinforced by the findings of the systematic review we conducted on ABO groups and stroke. In contrast to results obtained from venous TE systematic review, where almost a two fold increased risk was found with non-O groups vs. O group.

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Tarantino, E. "THE ROLE OF CYCLOOXYGENASE-1 (COX-1) AND CYCLOOXYGENASE-2 (COX-2) IN A VENOUS THROMBOSIS MOUSE MODEL." Doctoral thesis, Università degli Studi di Milano, 2016. http://hdl.handle.net/2434/353697.

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Background: Deep vein thrombosis (DVT) is a serious national health problem, and pulmonary thromboembolism (PE) represents the life-threatening most common complication. Venous thromboembolism (VTE), including both these conditions, is traditionally treated with anticoagulant drugs. In particular, vitamin K antagonists and heparins are usually used in the reduction of thrombus development and in secondary prevention. However, the use of these drugs has several limitations: wide variability dose/response relationship between patients and in the same patient, multiple interactions with other drugs/foods, variability of daily doses, need of periodic withdrawals of blood during therapy, problems of overdosing. Then, the discovery of new drugs for VTE needs. The cyclooxygenase isoenzymes, COX-1 and COX-2, catalyse the formation of prostaglandins and, thromboxane from arachidonic acid, and play a critical role in thrombosis. Recent meta-analysis suggests that low-dose aspirin (ASA) reduces the rate of VTE recurrence. In contrast, the clinical use of COX-2 inhibitors seems associated with increased risk of venous thrombosis. However, the role of COX-1 and COX-2 in venous thrombosis remain unclear. Aim: We investigated the impact of COX-1 and COX-2 enzymes in venous thrombosis in order to identify the molecular mechanisms responsible for this effect and develop new therapeutic strategies to prevent venous thrombosis. In particular, we focused on the impact of inhibition of COX-pathway on leukocyte activation, important regulators of formation and propagation of venous thrombus. Methods and Results: Using in vivo and in vitro approaches, we provide evidence that: a) thromboxane, produced by platelets, triggers activation of leukocytes, with consequent development and propagation of venous thrombus induced by inferior vena cava ligation. In particular, we showed that ASA, by inhibiting irreversibly platelet COX-1, prevents platelet thromboxane production resulting in decreased venous thrombosis. b) COX-2 deletion induces platelet hyper-activity and hyper-coagulation state, associated with a reduced fibrinolysis and formation of bigger thrombi. In this scenario, the high levels of tissue factor observed in leukocytes of COX-2KO mouse may explain the positive association observed between administration of COX-2 inhibitors and VTE. Thanking advantage of an accurate, and clinically relevant, technique such as ultrasonography, we are setting a method helpful to monitor thrombus growing and to better understand the pathophysiology of venous thromboembolism. Conclusion: In conclusion, data obtained show that the inhibition of COX-1 and COX-2 in a venous thrombosis mouse model could lead to opposite effect on the thrombus development, stabilization and resolution. In particular, COX-1 inhibition is responsible of an impairment development and growth of venous thrombus, with a mechanism most likely dependent of TXA2/TP pathway. In contrast, COX-2 inhibition caused an increased in thrombus development, growing accompanied with reduction in the thrombus resolution. All data obtained support evidences that both COX-1 and COX-2 play a key role in DVT, opening the way to novel therapeutic approaches.

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Brock, Sheila Anne. "Compression and Doppler ultrasound of deep vein thrombosis in patients on tuberculosis treatment." Thesis, Cape Peninsula University of Technology, 2013. http://hdl.handle.net/20.500.11838/1570.

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Thesis submitted in fulfilment of the requirements for the degree of Doctor of Technology: Radiography in the Faculty of Health and Wellness Sciences at the Cape Peninsula University of Technology 2013
Background. Ultrasound has until recently been regarded as a sophisticated examination reserved for tertiary health care. In reality it is well suited to the district or primary health-care situation. A DVT (deep vein thrombosis) is an important complication of the treatment of TB and this can lead to more devastating sequelae such as a pulmonary embolus. Many DVTs are clinically silent, making the diagnosis difficult. Method. This study was a prospective, longitudinal observational study. The study documented the incidence of DVTs and their onset, assessed certain aspects in an attempt to identify some risk factors, and noted the most common position of the DVT in a TB population. The feasibility of a sonographer-led ultrasound clinic for the diagnosis of DVTs was also assessed. This was achieved by screening the in-patient population at a district TB hospital. The participants received up to four routine duplex Doppler compression ultrasound examinations of the venous system of the lower extremities on week 0, week 4, week 8 and week 14. In addition a single abdominal ultrasound was performed at week 0. Results The incidence of DVTs in this TB population was 15.3%. A median of day 10 from commencing TB treatment was identified as the most common day to develop a DVT. The popliteal vein was the most frequent position for a DVT. Several statistically significant factors were identified, including a decreased ambulatory status, TB regimen and the use of anticoagulants. Only 52% of the DVTs were clinically symptomatic. The clinical evaluation for a DVT diagnosis in this study population had a sensitivity of 52.4% and a specificity of 65.3%. The positive predictive value (PPV) was 21.7%. Of the abdominal ultrasound reports there were 75.5% (281) abnormal reports, 22.5% (n = 90) normal reports and 4.5% (n = 18) with no report. Conclusion This body of work has shown how an effective ultrasound service can be provided at a district level TB hospital successfully administered by a trained ultrasonographer. This also facilitated a screening service to diagnose both symptomatic and asymptomatic deep vein thromboses in newly diagnosed tuberculosis patients. This study confirmed a higher rate of DVT in newly diagnosed TB patients than has been previously seen. It also provided detail on additional risk factors. The study illustrates the poor performance of clinical signs and symptoms as a trigger for further investigation for the confirmation of a DVT. Given the frequency and impact of the embolic complications of DVT, this study provides a strong justification for further research into routine serial ultrasonic screening and/or prophylactic antithrombolytics in newly diagnosed TB patients. As well as the DVT ultrasound scans there was the ancillary service offered by the research sonographers. This included an abdominal scan that detected abdominal pathology in 75% of the scans performed. An ultrasound scan is not pathognomonic but it does provide significant insight into the extent of some of the abdominal pathologies seen in TB patients. The information provided from this study gives a good indication of the problem that DVTs present in this population and the complexities of the disease TB. It is hoped that the results from this study will better equip the medical team in the non-tertiary situation to be vigilant for the presence of a DVT and educate them on the usefulness of the ultrasound scan.

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Farrell, Laura-Lee Amelia Catherine. "Prosthetic Vein Valve: Delivery and In Vitro Evaluation." Thesis, Available online, Georgia Institute of Technology, 2007, 2007. http://etd.gatech.edu/theses/available/etd-04042007-180135/.

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Sobieraj, Diana M., Craig I. Coleman, Vinay Pasupuleti, Abhishek Deshpande, Roop Kaw, and Adrian V. Hernández. "Comparative efficacy and safety of anticoagulants and aspirin for extended treatment of venous thromboembolism: A network meta-analysis." Elsevier B.V, 2015. http://hdl.handle.net/10757/346496.

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Diana.sobieraj@hhchealth.org
Objective To systematically review the literature and to quantitatively evaluate the efficacy and safety of extended pharmacologic treatment of venous thromboembolism (VTE) through network meta-analysis (NMA). Methods A systematic literature search (MEDLINE, Embase, Cochrane CENTRAL, through September 2014) and searching of reference lists of included studies and relevant reviews was conducted to identify randomized controlled trials of patients who completed initial anticoagulant treatment for VTE and then randomized for the extension study; compared extension of anticoagulant treatment to placebo or active control; and reported at least one outcome of interest (VTE or a composite of major bleeding or clinically relevant non-major bleeding). A random-effects Frequentist approach to NMA was used to calculate relative risks with 95% confidence intervals. Results Ten trials (n=11,079) were included. Risk of bias (assessed with the Cochrane tool) was low in most domains assessed across the included trials. Apixaban (2.5mg and 5mg), dabigatran, rivaroxaban, idraparinux and vitamin K antagonists (VKA) each significantly reduced the risk of VTE recurrence compared to placebo, ranging from a 73% reduction with idraparinux to 86% with VKAs. With exception of idraparinux, all active therapies significantly reduced VTE recurrence risk versus aspirin, ranging from a 73% reduction with either apixaban 2.5mg or rivaroxaban to 80% with VKAs. Apixaban and aspirin were the only therapies that did not increase composite bleeding risk significantly compared to placebo. All active therapies except aspirin increased risk of composite bleeding by 2 to 4-fold compared to apixaban 2.5mg, with no difference found between the two apixaban doses. Conclusion Extended treatment of VTE is a reasonable approach to provide continued protection from VTE recurrence although bleeding risk is variable across therapeutic options. Our results indicate that apixaban, dabigatran, rivaroxaban, idraparinux and VKAs all reduced VTE recurrence when compared to placebo. Apixaban appears to have a more favorable safety profile compared to other therapies.
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Edwards, David. "Pre-Clinical Evaluation of a Novel Radiotracer for the Diagnosis of DVT and Pulmonary Embolism." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7321.

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Rosenqvist, Kerstin. "Transjugular intrahepatic portosystemic shunt in the treatment of symptomatic portal hypertension." Doctoral thesis, Uppsala universitet, Radiologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-321538.

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Portal hypertension (PHT) is a condition with serious complications, such as variceal bleeding, refractory ascites and bowel ischemia. The cause of PHT may be pre-, intra- or post-hepatic. Initial treatment is pressure-reducing drugs and the treatment of acute symptoms. Ten patients presented with severe abdominal pain and acute portomesenteric venous thrombosis. Their response to systemic anticoagulation was insufficient. Treatment with primary continuous thrombolysis by a transhepatic or transjugular approach in four patients resulted in major complications, incomplete recanalization and a 75% survival rate. Treatment with repeated transjugular thrombectomy (TT) combined with the creation of a transjugular intrahepatic portosystemic shunt (TIPS) achieved near complete recanalization, prompt symptom relief and 100% survival in five patients treated with this method as the primary intervention. In one patient, treated with TT and TIPS secondary to surgical thrombectomy and bowel resection, the outcome was fatal. Nineteen patients with portal vein thrombosis presented with acute or threatening variceal bleeding or refractory ascites. TIPS was feasible in 16 of the 18 patients in whom it was attempted and symptom relief was achieved in the majority of them. In 14 patients with Budd-Chiari syndrome, 13 patients were treated with TIPS, four of them after previous liver vein angioplasty. The 5-year transplantation-free survival rate was 100% in patients treated with primary TIPS. In 131 patients with variceal bleeding treated with TIPS, the survival at 12 months in patients with and without cirrhosis was 70% and 100% respectively and in accordance with previous studies. A high Child-Pugh score prior to TIPS and severe HE within 12 months after TIPS was related to an increased mortality. The occurrence of HE after TIPS did not correlate with the PSG after TIPS. Re-bleeding within 12 months after TIPS occurred in 10 patients and was associated with TIPS dysfunction. In conclusion, endovascular intervention, mainly TIPS, seems to be safe and effective for treating patients with complications of PHT, regardless of the underlying cause of disease and site of venous blood flow obstruction. HE may occur more frequently after TIPS than medical and endoscopic treatment, but is often mild and easily treated. In selected patients with PHT, TIPS may improve survival.

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Swekwi, Natta. "The effects of co-prescription of warfarin and cardiovascular medicines among atrial fibrillation patients and/or deep vein thrombosis patients in Queensland, Australia." Thesis, Griffith University, 2020. http://hdl.handle.net/10072/398411.

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Introduction: Warfarin has been an anticoagulant for prophylaxis and treatment of venous thrombosis and thromboembolism in patients with atrial fibrillation for more than five decades. Due to its narrow therapeutic index, warfarin management is considerably challenging. A small change in plasma concentration can cause adverse effects which are sometimes life threatening. Thus, it is essential to monitor it closely by measuring International Normalised Ratio (INR) and Time in Therapeutic Range (TTR). Many factors such as age, weight, BMI, gender, smoking status, comorbidity, genetic factors and drug interaction can affect warfarin treatment. Additionally, warfarin users frequently have hypertension which leads to co-administration with a cardiovascular medicine, including antiarrhythmic medicine, that may interact with warfarin. Hence, this study aims to determine the effect of these medications on warfarin control in the clinical setting during long-term therapy. Method: A retrospective data analysis was conducted for patients receiving warfarin therapy for AF and DVT at a private pathology practice in Queensland from November 2007 to October 2014. Data included age, gender, current medications, comorbidities, INR test dates and results, reported bleeding and stroke events. The primary outcome was TTR and the secondary outcome was the number of adverse events, namely major bleeding, minor bleeding and stroke. The analysis consisted of three steps. The first step analysed all patients, while the second step analysed patients after excluding drug interaction with warfarin. Both the first and second steps were analysed regarding the use of medicine grouping within each drug classification, namely digoxin, Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II receptor blockers (ARBs), Beta-blockers (BBs) and Calcium channel blockers (CCBs). The third step was to analyse patients after excluding drug interaction with warfarin with regard to the use of particular drugs within each drug classification. Results: From a total of 4,494 patients, 52.2% of patients were on BBs while one-fourth of patients were on ARBs (27.2%) and CCBs (25.3%). Around one-third of patients received ACEIs (32.8%) and digoxin (30.0%). In all patients, the users of drug classifications namely ACEIs, ARBs, BBs and CCBs had a higher median TTR as opposed to non-users. After excluding drug interaction patients, there were no significant differences between users and non-users of each drug classification in median TTR. In the third step analysis, users of felodipine had a higher median TTR as opposed to non-users of CCBs (90.40, 84.30-96.38 vs 83.71, 76.62-89.58, p=0.008). In addition, the use of enalapril and telmisartan saw an increase in numbers of minor bleeding (enalapril: 3 (42.9%) vs 64 (11.9%), p=0.0132 and telmisartan: 11 (21.6%) vs 73 (11.8%), p=0.0424). Users of amlodipine, atenolol, lercanidipine, and telmisartan had a higher risk of bleeding (amlodipine: 2.00, 1.00-2.00, p=0.008; atenolol: 2.00, 1.00-2.00 vs 1.00, 1.00-2.00, p<0.001; lercanidipine: 2.00, 1.00-2.00 vs 1.00, 1.00-2.00, p=0.013 and telmisartan: 2.00, 1.00-2.00 vs 1.00, 1.00-2.00, p<0.001). Furthermore, the risk of stroke was higher among users of amlodipine, atenolol, felodipine, lercanidipine and metoprolol (amlodipine: 4.00, 3.00-5.00 vs 3.00, 2.00-4.00, p<0.001; atenolol 4.00, 3.00-5.00 vs 3.00, 3.00-4.00, p<0.001; felodipine 4.50, 4.00-5.00 vs 3.00, 2.00-4.00, p<0.001; lercanidipine: and metoprolol: 4.00, 4.00-5.00 vs 3.00, 3.00-4.00, p<0.001). Conclusion: The use cardiovascular drugs in our study did not negatively impact either warfarin control or event numbers. Additionally, the users and non-users in all drugs in our study had a high level of TTR (more than 80%). Thus, these drugs are safe to administer together with warfarin in a long-term therapy under close monitoring by a physician or warfarin care program. However, the effects of enalapril and telmisartan on minor bleeding are still unknown and our finding still needs further analysis to confirm these results.
Thesis (Masters)
Master of Medical Research (MMedRes)
School of Medical Science
Griffith Health
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Baar, Simon [Verfasser], and Stefan-Martin [Akademischer Betreuer] Brand. "The role of HIVEP1 in endothelial platelet interaction in the context of venous thrombosis / Simon Baar ; Betreuer: Stefan-Martin Brand." Münster : Universitäts- und Landesbibliothek Münster, 2019. http://d-nb.info/1188706500/34.

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Pereira, Mora José Mauricio [Verfasser]. "Central venous catheter induced thrombosis in dogs : occurrence under an antithrombotic treatment regimen and possible indicators / José Mauricio Pereira Mora." Hannover : Stiftung Tierärztliche Hochschule Hannover, 2020. http://d-nb.info/1225740339/34.

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Bittar, Luis Fernando 1980. "Avaliação de alterações moleculares nos genes do FVW e da ADAMTS 13 e sua correlação com os niveis plasmaticos de FVIII e FVW em pacientes com trombose venenosa profunda." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310145.

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Orientador: Joyce Annichino-Bizzacchi
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Níveis elevados de fator VIII (FVIII) são um fator de risco independente e prevalente para trombose venosa profunda (TVP), e tem influência do FvW. A ADAMTS13 é responsável pela modulação do tamanho molecular do FvW, clivando os multímeros de altíssimo peso molecular. Alterações moleculares no gene da ADAMTS13 têm correlação com sua atividade. Neste estudo avaliamos a prevalência do polimorfismo A4751G no gene do FvW (região de ligação com a ADAMTS13), os polimorfismos C1797T e C1852G e a mutação C4006T no gene da ADAMTS13 em 435 pacientes com TVP (156M/279F; idade mediana=37) e 580 controles (170M/410F, idade mediana=35). Investigamos a relação entre os genótipos e a dosagem de FVIII e FvW no plasma e o risco de TVP. A dosagem de FVIII:C foi realizada por método coagulométrico de um estágio, e as dosagens de FVIII:Ag e FvW:Ag por método imunoenzimático. As alterações moleculares foram determinadas por PCR e digestão com enzimas específicas, ou SSCP e sequenciamento para confirmação. Pacientes com TVP mostraram níveis significantemente aumentados de FVIII:C (203.7 UI/dl vs. 127 UI/dl; p<0.001), FVIII:Ag (109.6 UI/dl vs. 82.4 UI/dl; p<0.001) e FvW:Ag (154.2 UI/dl vs. 108 UI/dl; p<0.001) quando comparados com o grupo controle. Não houve diferença significativa entre os grupos na prevalência das alterações moleculares estudadas. Os indivíduos com genótipo AG (FvW A4751G) apresentavam níveis significativamente reduzidos de FVIII:C (p=0.04). Embora também tenha demonstrado uma discreta associação com níveis diminuídos de FvW:Ag, esta não foi estatisticamente significativa (p= 0.07). Os indivíduos com genótipo CG (ADAMTS13 C1852G) apresentavam níveis significativamente aumentados de FVIII:Ag (p=0.05) e FvW:Ag (p= 0.01). Apesar da relação com diminuição do FVIII o polimorfismo A4751G não mostrou um efeito protetor para TVP. O polimorfismo ADAMTS13 C1852G está associado à diminuição desta metaloprotease, e sua associação com níveis aumentados de FVIII:Ag e FvW:Ag neste estudo favorece essa hipótese.
Abstract: Elevated levels of factor VIII (FVIII) are a prevalent and independent risk factor for deep venous thrombosis (DVT), and are affected by von Willebrand factor (vWF) levels. ADAMTS13 is responsible for the modulation of the molecular size of vWF, cleaving the ultra large multimers. Mutations and polymorphisms in the ADAMTS13 gene are related with its activity. This study evaluated the prevalence of polymorphism A4751G in the vWF gene, polymorphisms C1797T, C1852G and the mutation C4006T in the ADAMTS13 gene in 435 patients with DVT and 580 healthy controls. Subsequently, we investigated the relationship between the genotypes and plasma levels of FVIII and vWF and DVT risk. FVIII:C was measured by a one-stage clotting method, and FVIII:Ag and vWF:Ag were measured by chromogenic method. The molecular changes were determined by restriction endonucleases or single strand conformation polymorphism followed by sequencing. Statistical test:U Mann-Whitney, = 0.05. Patients with DVT had higher plasma levels of FVIII:C (mean 203,7 UI/dl vs. 127 UI/dl; p<0.001), FVIII:Ag (mean 109,6 UI/dl vs. 82,4 UI/dl; p<0.001) and vWF:Ag (154,2 UI/dl vs. 108 UI/dl; p<0.001) when compared to controls. We observed no statistical difference in the prevalence of all molecular changes studied between patients and controls. A4751G heterozygotes had significantly reduced levels of FVIII:C (p=0,04). Althought there was a slight association with reduced levels of vWF: Ag, this association was not statistically significant (p= 0,07). C1852G heterozygotes had significantly elevated levels of FVIII:Ag (p=0.05) and vWF:Ag (p= 0,01). Despite the relative decline of FVIII:C with the A4751G polymorphism there was no protective effect for DVT. The C1852G polymorphism is associated with a reduction of ADAMTS13, and its association with increased levels of FVIII: Ag and vWF: Ag observed in this study supports this hypothesis.
Mestrado
Biologia Estrutural, Celular, Molecular e do Desenvolvimento
Mestre em Fisiopatologia Médica

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Dissertations / Theses on the topic 'Venous thrombosis'

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