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Echenique, Javier Jacobo. "Thrombotic fingerprints for the enhanced prediction of thrombosis." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/39880.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2007.Includes bibliographical references (leaves 111-114).
Controlled thrombosis initiates and regulates tissue repair and remodeling in the vessel wall. Processes from heart attack to stroke, and deep vein thrombosis to pulmonary embolism, are all derived from unrestricted clotting. The frustrating aspects of these diseases lie not only in the difficulty of their timely diagnosis, but in the selection of appropriate therapy, titration of intervention, and identification of patients at risk. Assays like the INR, PTT, and ACT can follow the course of specific pathways that govern activation of specific coagulation factors or platelet function, but they do not provide the insight into mechanism, risk and potential therapeutic benefit. We posit that elucidation of the complex dynamics of clot generation requires an integrated assessment that takes into account all of the factors driving thrombosis simultaneously. Virchow's Triad, has for years been identified as the three critical parameters of clot formation. We propose to examine an individual's clot propensity and response to therapy on minute blood samples, in virtual real time, across a range of flow rates, blood state, and wall conditions with the use of our newly developed in vitro high-throughput testing device.
(cont.) In this manner we will generate a unique thrombotic fingerprint that defines an individual's risk of clotting at a specific point in time over a range of stresses. This fingerprint can aid in tailoring therapeutic clinical treatments, determining the duration and dose of therapy, and assist in clinical trial management and establishment of clinical norms.
by Javier Jacobo Echenique.
S.M.
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Mendez, Rojano Rodrigo. "Thrombosis modeling in blood coated medical devices." Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTS088/document.
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La thrombose est la formation d’un caillot sanguin (thrombus) dans le système cardiovasculaire. Il s’agit d’un des principaux problèmes des dispositifs biomédicaux en contact avec du sang. Toutefois, les biomatériaux utilisés jusqu’à présent dans ces dispositifs déclenchent la coagulation à travers le système de contact. Ce système n’a pas été pris en compte dans les modèles de thrombose dédiés aux dispositifs, alors que son importance pour la thrombose a été récemment remarquée. L’objectif de cette thèse est d’introduire les réactions de coagulation initiées par le système de contact dans la modélisation de la thrombose liées aux dispositifs. Un nouveau modèle réduit pour la génération de thrombine est proposé en incluant l’activation par contact. Le modèle arrive à calculer la formation de thrombine dans du plasma physiologique et du plasma déficient en prothrombine. Une fois réalisée, l’approche réduite est incluse dans un modèle de croissance du thrombus basé sur l’activité des plaquettes. Cette nouvelle stratégie est utilisée pour calculer la formation du thrombus dans une configuration académiqueThrombosis, which is the formation of a blood clot (thrombus) in the vascular system, is one of the major issues of blood-coated medical devices. To reduce thrombosis risk in this type of devices, computational fluid dynamics has been used. Up to date, bio-material surfaces used in blood coated devices initiate blood coagulation through the contact activation system. This system has not been considered in models dedicated to devices, even though its importance in thrombosis has been recently highlighted. The objective of this thesis is to introduce device-triggered coagulation reactions in the modeling of device-related thrombosis.A novel reduced kinetic model including the contact activation system is proposed. The model correctly captures thrombin formation in physiological and prothrombin deficient platelet-poor-plasma. The reduced set of reactions is then included in a platelet-based model for thrombus formation considering platelet activation by thrombin. This approach is used to study thrombus formation in an academic configuration
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Bark, David Lawrence Jr. "The hemodynamics during thrombosis and impact on thrombosis." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/37258.
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Atherothrombosis can induce acute myocardial infarction and stroke by progressive stenosis of a blood vessel lumen to full occlusion. The goal of this research is to determine what shear rates are pertinent to an occluding blood vessel, the rate of thrombus growth relative to wall shear rates, and to develop a predictive model for estimating length of time to thrombus occlusion for a given atherosclerotic lesion. Computational studies of severely stenotic idealized vessels were performed to investigate the wall shear rates that may exist. The study shows that maximum shear rates in severe short stenoses were found to exceed 250,000 1/s (9,500 dynes/cm2). We utilize an in vitro experiment consisting of blood flow through a collagen coated stenosis to study the rate of thrombus growth. Growth is monitored through light microscopy and a camera. Computational fluid dynamics are used to determine shear rates along the thrombus surface as it grows. We found a strong positive correlation between thrombus growth rates and shear rates up to 6,000 1/s after a log-log transformation (r=0.85, p<0.0001). Growth rates at pathologic shear rates were typically 2-4 times greater than for physiologic shear rates below 400 s-1. To determine whether transport or kinetic binding limits the rate of thrombus growth, a computational model of platelet transport was developed. The model allows for thrombus growth by occluding computational cells. We show that thrombus is transport rate-limited for shear rates below 6,000 1/s, while it is more likely to be kinetic rate-limited for higher shear rates. Predictions of occlusion times based on the model demonstrate that increases in stenosis severity results in decreased time to occlusion.
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Maclean, Jessica Amy Ann. "Novel approaches to enhance the thrombolytic potential of tissue plasminogen activator (tPA) therapy in stroke." Thesis, University of Sydney, 2020. https://hdl.handle.net/2123/23147.
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Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) remains the primary pharmacological therapy for acute ischaemic stroke. Despite some significant clinical benefit at three months, rtPA-mediated recanalisation rates remain suboptimal in over 50% of patients receiving this therapy, and cerebral reperfusion is not always achieved with arterial reopening. The aim of these doctoral studies was to investigate novel adjunctive antithrombotic approaches to enhance rtPA-mediated large artery recanalisation and improve cerebral perfusion in a mouse model of stroke. Initial studies focused on the development of the in situ carotid artery thrombo(ly)sis (iCAT) model, the first mouse model of electrolytic-induced carotid artery thrombosis and graded unihemispheric hypoperfusion leading to cerebral infarction. This model allows for the simultaneous real-time assessment of recanalisation, cerebral perfusion and end-organ damage. Extensive characterisation of the iCAT model validated its suitability for the assessment of thrombolytic and adjunctive antithrombotic therapy. Combining rtPA with the anticoagulant therapy (Argatroban) enhanced recanalisation (41.9% vs 22.2% rtPA alone) and significantly improved cerebral perfusion (laser speckle contrast imaging), leading to a moderate reduction in infarct volumes (TTC) at 24 hours. Collectively, these studies present a novel mouse model for the real-time assessment of recanalisation, reperfusion and end-organ damage.
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Landskroner, Kyle Alan. "Thrombosis and Thrombolysis: Emphasis on Hemophilia and Effect of Clot Dissolution with Plasmin." NCSU, 2005. http://www.lib.ncsu.edu/theses/available/etd-08142005-145317/.
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The purpose of this research was to understand the mechanisms in which blood clots form and are degraded. The research studies examined the role of an endogenous protease, plasmin, which is found in all vertebrates, and the optimal doses of plasmin required to dissolve blood clots. When we investigated clot lysis with plasmin we examined blood clots from several species to which varying concentrations of plasmin were added, as well as varying methods of plasmin administration. The results of these studies not only highlighted important dose-response relationships of plasmin, but also demonstrated differences in the effect of human plasmin to dissolve blood clots compared to blood clot from the species tested. Porcine clots, in particular, were more resistant to lysis compared with human clots, while ovine clots had similar lysis compared with human clots. In addition, this research demonstrated that plasmin?s effectiveness to lyse thrombi increases with an increase in clot surface area, e.g, by fragmentation, or when plasmin is administered as an intrathrombic administration. In separate studies, to investigate clot formation, we uesd mice that lack the FVIII protein. For these experiments we investigated the formation of blood clot formation using rotational thromboelastography (ROTEG) that measures the formation of fibrin in whole blood. This method was shown to be extremely sensitive to low levels of factor VIII protein and may have applications to classify particular phenotypes of hemophilia patients, or as a research tool to evaluate novel FVIII molecules.
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Clouston, Hamish. "Thrombosis in colorectal cancer." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/thrombosis-in-colorectal-cancer(43d5ef8e-6c59-4fc6-b02c-695898e634d5).html.
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Thrombosis and colorectal cancer have a bi-directional relationship. The presence of a colorectal malignancy results in an increased risk of developing a thrombosis and the presence of a thrombosis results in a worse cancer prognosis. The physiology causing this is at present unclear but it is proposed that proteins from the tissue factor (TF) pathway may be the instigator of this bi-directional relationship. The in-vitro studies have shown that in colorectal cancer TF impairs that action of colorectal cancer stem cells as demonstrated by reduced cancer sphere formation and also lower expression of the stem cell marker ALDH. The ability for a colorectal cell to avoid anoikis is impaired by a reduced TF level. Proliferation is affected by the level of expression of TF with a significant increase in proliferation with additional expression of TF. The increase in proliferation is further increased by the presence of TF’s ligand factor VIIa. Paradoxically reduced expression of TF also increases colorectal cancer expression. The ERK1/2 pathway offers a possible method by which TF and factor VIIa may exert their proliferative effects. In the prospective clinical cohort study (CHAMPion) abnormal expression of TF pathway proteins (TF, PAR1, PAR2 and thrombin) by both malignant epithelial and cancer associated stromal cells has been demonstrated. The stromal expression was independent of the epithelial expression and was only in stroma in close contact (0.1mm) with epithelial cells suggesting that the TF pathway proteins may have a role in stromal/epithelial communication. There was no link between the expression of TF pathway proteins and clinicopathological markers of a poor prognosis. The plasma expression of markers of TF pathway activation did not demonstrate any role as a biomarker for colorectal cancer or prognosis. The CHAMPion study has demonstrated that 7% of patients undergoing surgery for colorectal cancer have asymptomatic pre-operative DVTs present. A further 6% who were DVT free pre-operatively developed a DVT in the peri-operative period despite receiving venous thromboprophylaxis in line with current national guidelines. Pre-operative d-dimer may have the potential to identify those patients at risk of a post-operative VTE.This thesis establishes the role that TF has in promoting proliferation and anoikis resistance. It also confirms the abnormal expression of TF pathway proteins by colorectal cancer epithelial cells and for the first time demonstrates abnormal expression by the cancer associated stroma. The interaction between the stroma and epithelial cells, combined with the cellular effects of TF suggests that targeting this interaction may have a therapeutic role. The incidence of DVTs pre-operatively suggests that screening patients for the asymptomatic presence of a DVT may have an impact on their clinical outcome. The development of DVTs despite prophylaxis suggests that the level of anticoagulation is insufficient and current guidelines need to be revisited.
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Bruce, David. "Antithrombin : structural variants and thrombosis." Thesis, Open University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386084.
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Gray, E. "Lipoproteins, blood coagulation and thrombosis." Thesis, Open University, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372834.
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The main aim of this study was to investigate the involvement of plasma lipoproteins in the blood coagulation system and the implications of this relationship in the pathogenesis of thrombosis. This study has shown that lipid peroxide-induced thrombin generation is caused by a two-fold mechanism: direct interaction of lipid peroxides with lipoprotein phospholipids and inhibition of anti-thrombin III via its heparin-binding site. Experiments using purified lipoproteins have shown that triglyceride-rich lipoproteins, i.e. chylomicra and very low density lipoproteins, are sources of procoagulant activity, whereas low density and high density lipoproteins have little effect. Further work with phospholipids extracted from chylomicra has demonstrated that lipid peroxides interact with the phospholipid component of the lipoprotein molecule and, possibly through an increase in overall negative charge, provide a suitable surface for the binding of clotting factors. Subcutaneous injection of potent lipase releasers, which are weak in vitro anticoagulants, reduce the ex vivo thrombin-generating activity of post-infusion plasma. This reduction in procoagulant activity is caused by the phospholipase action of the hepatic tri-glyceride lipase (HTGL) released. Human HTGL also enhances plasma anti-Xa activity, due to direct inhibition of Xa clotting activity, but the amidolytic activity of Xa is unaffected, thus implying that the serine site of Xa is not preferentially targeted. The phospholipid binding site of Xa appears to be involved, but this anti-Xa effect is not due to the phospholipase action of HTGL. The antithrombotic effects of heparin and heparin analogues may thus be partly due to the release of HTGL, which can reduce pro-coagulant activity via inhibition of lipid peroxide-induced thrombin generation and enhancement of plasma anti-Xa activity.
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Saraf, Smriti. "Assessment of thrombotic and thrombolytic status in patients with coronary artery disease and its relation to clinical outcomes." Thesis, University of Hertfordshire, 2014. http://hdl.handle.net/2299/15000.
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Background: Platelets provide the initial haemostatic plug at sites of vascular injury. They also participate in pathological thrombosis that leads to myocardial infarction, stroke and peripheral vascular disease. The outcome of an acute myocardial infarction depends not only on the formation and stability of an occlusive thrombus, but also on the efficacy of the endogenous thrombolytic process, which allows reperfusion of the infarct related artery and prevents recurrent ischaemic episodes. Various platelet function tests are available to measure the thrombogenic potential of an individual, but the sensitivity of these tests remain questionable as most of these tests use citrated blood and measure response to a particular agonist. Endogenous thrombolysis has been a neglected entity, and its beneficial effects on cardiovascular outcomes has not been studied in depth in the past, possibly as until recently there has been no available technique to measure spontaneous thrombolytic activity in native blood. The Global Thrombosis Test (GTT) is a new point of care tests that allows us to measure time to thrombus formation (Occlusion time: OT) using native blood, avoiding the use of agonists and making the test results more physiological. The GTT also measures the time to lyse this formed thrombi without use of any lytic agents (Lysis time: LT), allowing us to measure the patient’s endogenous thrombolytic potential. Aim: Our aim in this study was to detect patients who are at risk of future thrombotic events despite dual antiplatelet therapy, either due to prothrombotic tendency or due to impaired endogenous thrombolysis, and to determine if these two parameters were correlated. Methods: GTT was used to assess the thrombotic and thrombolytic activity in healthy volunteers, and in different patient populations. 100 healthy volunteers were tested using the GTT, and a normal range was established. 300 patients admitted to hospital with a diagnosis of acute coronary syndrome (ACS) were included in the study, and tested using the GTT after they had been stabilized on dual antiplatelet therapy (Aspirin and Clopidogrel). All these patients were followed up for a year, to determine if their baseline GTT results were a predictor of recurrent cardiac events. The primary endpoint of the study was major adverse cardiovascular events (MACE), which was a composite of cardiovascular death, nonfatal myocardial infarction, or stroke at 12 months. Results: All results were analysed using statistical package SPSS version 16.0 (SPSS Inc., Chicago, Illinois). The 100 healthy volunteers were all non-smokers, and were not taking any medications. There were 55 males and 45 females, and mean age was 38±11 years (range 22-76, IQR 11). OT was normally distributed with mean OT 377.80s, and using mean ± 2SD, we derived a normal range of 185-569s (200-550s). LT demonstrated a skewed distribution with values ranging between 457 – 2934s. Using log transformation, a normal range of 592 – 1923 (600- 2000s) was established for LT. OT and LT were both prolonged in ACS patients compared to normal volunteers (p< 0.001). No association was observed between OT and risk of major adverse cardiovascular events. LT was noted to be a significant and independent predictor of MACE in a multivariate model adjusted for cardiovascular risk factors. LT ≥ 3000 s was the optimal cutoff value for predicting 6 month MACE [hazard ratio (HR): 2.48, 95% CI: 1.2-4.8, P= 0.008] and cardiovascular death [HR: 4.04, 95% CI : 1.3-12.0, P= 0.012 ] and 12 month MACE [HR:1.9, 95% CI: 1.04- 3.5,P= 0.03] and cardiovascular death [HR: 3.9,95% CI: 1.34-11.9, P= 0.013 ]. LT ≥ 3000 s was observed in 23% of ACS patients. Conclusions: Our study suggests that endogenous thrombolytic activity based on lysis of platelet rich thrombi can be assessed by the point of care GTT assay, which can help in identification of ACS patients at high risk of future cardiac events. Prolongation of OT may be explained by the antiplatelet effects of Aspirin and Clopidogrel, as both these drugs prolong time to thrombus formation and hence increase OT. Further large studies are required to study factors which can reduce thrombogenic potential, and improve endogenous thrombolytic activity, which can be monitored using the GTT to improve cardiovascular outcomes.
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Wootton, David MacMullen. "Mechanistic modeling of occlusive arterial thrombosis." Diss., Georgia Institute of Technology, 1998. http://hdl.handle.net/1853/17351.
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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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Darbousset, Roxane. "Roles of polymorphonuclear neutrophils in thrombosis." Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM5071.
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L’hémostase est un processus physiologique permettant de préserver l’intégrité du système vasculaire et de prévenir une perte de sang en réponse à une blessure. En situation pathologique, comme dans le cas de cancers, d’infections ou de maladies cardiovasculaires, il peut y avoir activation de la cascade de coagulation entraînant la formation d’un thrombus.Dans cette étude, nous avons utilisé la microscopie intravitale dans un modèle de blessure au rayon laser pour comprendre les mécanismes cellulaires et moléculaires mis en jeu dans la formation d’un thrombus plaquettaire en conditions physiologiques et pathologiques lors du développement d’un cancer. La première partie de ce travail a consisté à décrire l’implication des polynucléaires neutrophiles dans la formation d’un thrombus. Nous montrons que les neutrophiles sont les premières cellules à s’accumuler au niveau du site de blessure et représentent la principale source de facteur tissulaire menant à la génération de fibrine et à la formation du thrombus. Ces neutrophiles sont nécessaires au recrutement de cellules endothéliales progénitrices (Endothelial colony- forming cells, ECFCs), qui sont des cellules capables de jouer un rôle important dans la réparation vasculaire. Dans une seconde partie, nous avons déterminé, dans des modèles murins adaptés, l’implication de l’activation du FT et des plaquettes dans la thrombose associée au cancer. En conclusion, notre travail donne de nouvelles perspectives dans la compréhension du rôle pathophysiologique des neutrophiles, des cellules progénitrices endothéliales et des plaquettesHemostasis is a physiological process to preserve the integrity of the vascular system and to prevent blood loss in response to injury. In pathological conditions, such as cancers, infections or cardiovascular diseases, the blood coagulation cascade can be activated, leading to the formation of a platelet thrombus.Using a laser-injury model coupled with a high-definition, high-speed camera, we explored the cellular and molecular mechanisms involved in thrombus formation in physiological and in pathological conditions associated with the development of a cancer. The first part of this work describes the role of polymorphonuclear neutrophils (PMNs) in thrombus formation. We show that PMNs are the first cells to accumulate at the site of injury and represent the main source of blood-borne tissue factor (TF), leading to the generation of fibrin and thrombus formation. We also show that once present at the site of injury, PMNs recruit Endothelial Progenitor Cells (endothelial colony-forming cells, ECFCs), which play a key role in vascular repair. The second part of this work we determined, in dedicated mouse models, the involvement of TF and platelet activation in thrombosis associated with cancer. Together, our findings provide new perspectives in the understanding of the pathophysiological role of polymorphonuclear neutrophils, Endothelial Progenitor Cells and platelets
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Pépin, Marion. "Caractérisation de nouveaux médiateurs entre cancer, inflammation et thrombose : ADAMTS13, PSGL-1 et Siglec-5." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS571/document.
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La maladie cancéreuse et la maladie thrombotique sont des problématiques fréquentes et graves rencontrées en pathologie humaine et en santé publique. Elles ont une relation réciproque médiée par des interactions cellulaires et des mécanismes moléculaires complexes faisant intervenir des acteurs de l’hémostase et de l’immunité. Tout ou partie de ces phénomènes rendent en effet compte du processus d’inflammation et de réponse de l’organisme à l’agression. La caractérisation de certains médiateurs moléculaires ayant des rôles connus dans l’hémostase et l’inflammation peut nous permettre d’améliorer la compréhension de ces phénomènes et de proposer des pistes de réflexion diagnostiques ou thérapeutiques.Nous nous sommes donc intéressé au couple facteur Willebrand/ADAMTS13 : une protéine clé de l’hémostase dont le taux est influencé par les processus inflammatoires et sa protéase régulatrice. Cette étude menée chez des patients atteints de cancer nous a permis de montrer que l’utilisation de ces protéines comme des biomarqueurs peut améliorer la stratification du risque individuel de thrombose pour les patients et donc d’améliorer la prise en charge thérapeutique. Le rôle de ces protéines dans la physiopathologie de ces mécanismes reste à préciser.Par ailleurs, sur la base de connaissances structurelles, nous avons l’émis l’hypothèse d’une interaction entre deux récepteurs de la surface des leucocytes, cellules-clés de la réponse inflammatoire. En effet, PSGL-1 (P-sélectine glycoprotéine ligand 1), récepteur présent sur une grande partie des leucocytes est le ligand de la P-sélectine sur l’endothélium vasculaire et joue un rôle majeur dans le roulement des leucocytes permettant leur recrutement aux sites de l’inflammation. PSGL-1 a une structure riche en acides sialiques. Le Siglec-5 est quant à lui un récepteur de structure proche des immunoglobulines qui lie des acides sialiques. Nous avons donc décrit et caractérisé la liaison entre ces deux protéines, et étudié son rôle dans le roulement des leucocytes in vitro et in vivo. Avant d’envisager toute application, il reste bien sûr à caractériser plus précisément les modalités de cette interaction (site de liaison, etc…) et son effet dans d’autres mécanismes régulés par l’interaction PSGL-1/P-sélectine comme la formation du thrombusCancer and thrombosis are frequent and serious concerns in human pathology and public health. This conditions are known to share closed relationships, and reciprocal promotion involving cellular interactions and complex molecular mechanisms. Molecular pathways often involve hemostasis or immunity actors and participate in inflammation process, which can be either cause or consequence. Improved knowledge on molecular mediators at the crossroads of hemostasis and inflammation may allow best understanding of these mechanisms and improving therapeutic management.Thus, we studied Willebrand factor / ADAMTS13 couple : a key protein in hemostasis whose rate is influenced by inflammatory processes and its regulatory protease. This study in cancer patients shows that Willebrand factor and ADAMTS13 could be used as biomarkers to predict individual thrombosis risk and thus improve therapeutic management. Precise role of this proteins in cancer-mediated thrombosis remain unexplored.Furthermore, we hypothesized an interaction between two leukocyte receptors : PSGL-1(P-selectin glycoprotein ligand-1) and Siglec-5. Leukocytes, especially neutrophils are recruited to inflammation sites after a key step of rolling along vasculature. PSGL-1 expressed on the majority of leukocytes is P-selectin ligand and plays a major role in leukocyte rolling. PSGL-1 has a structure rich in sialic acids. Siglec-5 is an immunoglobulin-like receptor and binds sialic acids. Thus, we described and characterized the interaction between these two proteins, and studied its role in leukocyte rolling in vitro and in vivo. Before considering any application, the modalities of this interaction should further analyzed (binding site, etc. ...) and its effect in other mechanism involving PSGL-1/P-selectin interaction like thrombus formation
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Galanaud, Jean-Philippe. "Les thromboses veineuses méconnues des membres inferieurs : thromboses veineuses profondes distales et thromboses veineuses superficielles." Thesis, Montpellier 1, 2011. http://www.theses.fr/2011MON1T027.
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Rationnel: Bien qu'elles constituent la majorité des thromboses veineuses des membres inférieurs, les thromboses veineuses profondes (TVP) distale et les thromboses veineuses superficielles (TVS) ont été peu étudiées et leur significativité clinique et leur prise en charge sont débattues.Méthodes: Cette thèse collige les résultats des travaux effectués par J.P. Galanaud sur les TVP distales et les TVS à partir des études épidémiologiques OPTIMEV, POST et RIETE.Résultats commentés: TVP distale: La TVP distale n'a pas le même profil de facteur de risque que la TVP proximale. Sa mortalité associée à court terme est plus faible que celle des TVP proximales mais supérieure à celle de témoins confirmant qu'il s'agit d'une entité cliniquement significative. Les différences de profil de population et de complications entre ces deux types de TVP suggèrent que le rapport bénéfice/risque du traitement anticoagulant est différent. Il n'est donc pas légitime d'extrapoler les résultats des essais des TVP proximales aux TVP distales. Des essais spécifiques sont donc nécessaires.TVS: En cas de TVS le risque de TVP concomitante est élevé. Un examen écho-doppler doit être réalisé et devra au moins explorer l'ensemble du réseau profond du membre inférieur affecté. Sexe masculin et antécédents de TVP/Embolie pulmonaire constituent des facteurs prédictifs indépendants de récidive. Si certaines TVS peuvent être traitées avec succès sans traitement anticoagulant, celles associées à un cancer ou à une atteinte saphéno-fémorale sont à haut risque de récidive y compris après un traitement anticoagulant curatifBackground: Though they represent the majority of all lower limbs thromboses, isolated distal deep-vein thrombosis (DVT) (without symptomatic pulmonary embolism (PE)) and isolated superficial vein thrombosis (SVT) (without DVT or PE) have been poorly studied. Their clinical significance and management are under debate.Methods: Data from epidemiological multicenter prospective studies OPTIMEV, POST, RIETEResults and comments: Isolated distal DVT: Distal and proximal DVTs exhibit a different risk factor profile, the latter being more associated with chronic risk factors. Three-month mortality of distal DVT patient is lower than that of proximal DVT ones but is higher than that of controls. This evidences that distal DVT is a clinically significant finding. Differences in population profile and outcomes suggests that the benefit/risk ratio of anticoagulant treatment is not similar. Data from proximal DVT clinical trials should no longer be extrapolated to distal DVT.Isolated SVT: In case of SVT the risk of concomitant DVT is high. A compression ultrasonographic exam should be performed and at least explore the whole deep venous system of the affected limb. Male gender and history of DVT/Pulmonary embolism are independent predicators of recurrence. Some SVT can be safely treated without anticoagulants. On contrary, in patients with cancer or a sapheno-femoral junction involvement, the risk of deep venous recurrence is high even upon full therapeutic dose of anticoagulants
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Otten, Johannes Martinus Mattheus Bernardus. "Thrombosis and cancer a two way association /." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2002. http://dare.uva.nl/document/66385.
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Tabor, Caroline Mary. "Effects of air pollution on vascular thrombosis." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5577.
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Increases in air pollution, especially the particulate component, are associated with increased cardiovascular mortality, possibly through increases in thrombogenic mechanisms. The research presented in this thesis addresses the hypothesis that diesel exhaust particulates (DEP) increase thrombogenicity by impairing the release of tissue plasminogen activator (t-PA) from vascular endothelial cells, thus inhibiting the endogenous fibrinolytic mechanisms that promote thrombus breakdown. The initial aims of this work were to develop an in vivo model of thrombosis, to determine whether exposure to DEP did alter clotting. Initial attempts to develop the Folts’ model (which stimulates thrombus formation via arterial stenosis and mechanical injury), first in male C57/Bl6 mice and later in male Wistar rats, were unsuccessful. An alternative approach, using ferric chloride (FeCl3) to induce chemical injury to the rat carotid artery was found to produce reliable and reproducible thrombotic occlusion: this model was used for all subsequent experiments. The effects of DEP on thrombus formation were assessed in vivo by applying the FeCl3 model. DEP were administered via intratracheal instillation or tail vein injection 2, 6 or 24 hours prior to induction of thrombosis. The effects of DEP were compared with vehicle and suitable controls: carbon black (a clean carbon nanoparticle); quartz (a large non-carbon particle that causes well-characterised pulmonary inflammation). The time to thrombotic occlusion was significantly reduced 6h after intra-pulmonary instillation of DEP (0.5ml of a 1mg/ml suspension). In contrast, instillation of carbon black or quartz had no significant effect on thrombosis, despite causing greater pulmonary (increased neutrophils and levels of interleukin-6, tumour necrosis factor-α and C-reactive protein in bronchoalveolar lavage fluid) and systemic (C-reactive protein in plasma) inflammation than DEP. Direct administration of DEP (0.5mg/kg) to the blood stream resulted in an acute (2 hours after injection) increase in time to thrombotic occlusion in the absence of pulmonary inflammation. A similar (but less pronounced) effect was observed following administration of carbon black (0.5mg/kg). These data suggest that the DEP-mediated increase in thrombosis is independent of pulmonary and systemic inflammation. The mechanisms involved were addressed by measuring platelet-monocyte interactions (flow cytometry) and markers of the endogenous fibrinolytic system (ELISA). Exposure (either instillation of injection) to DEP significantly increased platelet-monocyte aggregation. Carbon black and quartz produced no such effect (but did increase platelet-platelet aggregation). t-PA antigen and activity were reduced, whilst PAI-1 and fibrinogen were increased, following either instillation or injection of DEP. The final aim was to develop a suitable dispersant for use in cell culture to determine whether DEP alter the expression (real-time polymerase chain reaction; rtPCR) and generation (enzyme-linked immunosorbent assay; ELISA) of t-PA and plasminogen activator inhibitor (PAI-1). Cell culture medium containing bovine serum albumin (0.5mg/ml; BSA) provided the best combination for DEP dispersal and maintenance of small particle size (<200nM), without detrimental effects on human umbilical endothelial cells (HUVECs). Exposure (6 and 24 hours) of HUVECs to DEP resulted in reduced basal and thrombin stimulated t-PA and PAI-1 expression. This was mirrored by reduced detection of t-PA and PAI-1 in culture medium. In conclusion, these investigations confirm that exposure to DEP is capable of increasing the rate of thrombus formation and that this is, in part, mediated by an alteration in the endogenous fibrinolytic system. These changes did not appear to be secondary to pulmonary or systemic inflammation. Whilst cell culture experiments suggested DEP could directly alter endogenous fibrinolytic activity in endothelial cells, there was no evidence from these experiments of DEP translocation into the systemic circulation. Thus, this work suggests that DEP is capable of increasing thrombus formation in vivo via several mechanisms. Similar changes may account for the increased thrombus formation in humans exposed to diesel exhaust in air pollution.
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Warwick, David John. "Deep vein thrombosis after total hip replacement." Thesis, University of Bristol, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283969.
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Martinod, Kim Lindsay. "Neutrophil extracellular traps in thrombosis and inflammation." Thesis, Harvard University, 2014. http://nrs.harvard.edu/urn-3:HUL.InstRepos:13064970.
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Neutrophil extracellular traps (NETs), chromatin released by activated neutrophils, were first described for their antimicrobial properties. NETs have a backbone of DNA and histones lined with microbicidal proteins such as neutrophil elastase. NET release has pathological consequences, particularly within blood vessels where NETs can trap red blood cells and platelets, thus contributing to thrombosis (Chapter 1-Overview). NET formation (NETosis) is an active and coordinated biological process involving many enzymatic components. One enzyme in particular, peptidylarginine deiminase 4 (PAD4), citrullinates histones and is required for chromatin decondensation during NETosis. Neutrophils from PAD4-deficient mice are unable to form NETs. We obtained these mice from our collaborator Dr. Yanming Wang, and thus were able to compare PAD4-/- mice to wild-type (WT) mice in mouse models where NETs are formed. These studies have allowed for investigation of the biological relevance of PAD4 and NETs in vivo in thrombotic and/or inflammatory disease.
This dissertation focuses on mouse models of deep vein thrombosis and of sepsis. In venous stenosis, thrombosis is initiated by restricting blood flow in the inferior vena cava (IVC). Here, PAD4-/- mice were greatly protected from thrombus formation (Chapter 2). Leukocyte rolling and platelet plug formation in response to vessel injury were unaffected, indicating that endothelial and platelet activation occurred normally in these mice. The mice did not exhibit any defects in hemostasis, and could be induced to produce deep vein thrombi by infusion of WT neutrophils that formed NETs as a part of the thrombus scaffold. Because there is potential to develop anti-NET therapies in thrombosis, I investigated if NET-deficiency would render mice immunocompromised (Chapter 3). PAD4-/- mice had similar mortality in the cecal ligation puncture model, and they were protected from shock in an LPS sepsis model where NETs are released in the absence of live bacteria. Therapies aimed at NET prevention or destruction would likely be beneficial without compromising host immunity. Thus, in summary, studying PAD4-deficient mice has revealed the impact of NETs in thrombotic/inflammatory disease and identified PAD4 as an attractive therapeutic target.
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Khan, Abdullah Rubiat (Emon). "Microparticles and their role in thrombosis in Behçet's Syndrome and their potential as a biomarker for thrombotic risk." Thesis, Imperial College London, 2017. http://hdl.handle.net/10044/1/58996.
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Thrombosis is common in Behçet’s Syndrome (BS), and there is a clear need both for a better understanding of causation and for biomarkers to enable thrombotic risk assessment. I set out to determine whether plasma microparticles (MP), particularly tissue factor expressing (TF+ MP) were increased in BS. Additionally, I investigated whether MP expressing tissue factor pathway inhibitor (TFPI) were also evident. Finally, I investigated whether these MP had a functional consequence role. MP were prepared from 88 BS patients and 72 healthy controls. The BS group contained 21 patients with a history of thrombosis (Th+) and 67 without (Th-). MP were identified by size and annexin V binding using flow cytometry, and were further analysed with antibodies to surface antigens. Assays used to assess the function of MP were an in-house coagulation lysis assay, calibrated automated thrombin generation assay and Factor Xa generation assay. Total MP numbers were increased in BS compared to HC, as were MP expressing TF and TFPI (all p < 0.001). Amongst BS patients, the Th+ group had increased total and TF positive MP (both p < 0.001) compared to the Th- group, but a lower proportion of TFPI positive MPs (p < 0.05). Consequently, the ratio of TFPI to TF MP counts (TFPI/TF) was significantly lower in Th+ versus Th- BS patients (p < 0.001), with no history of clinical thrombosis in BS patients with a TFPI/TF MP ratio > 0.7. Functional assays revealed no correlation with MP count. I conclude that MP expressing TF are increased in BS, more so in patients with thrombosis. An imbalance between microparticulate TF and TFPI may be pathophysiologically important for thrombosis in BS and may allow improved identification and appropriate treatment of thrombotic risk.
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Gómez, Puerta José Alfredo. "Antiphospholipid Syndrome: Expanding the Spectrum of Autoimmune Thrombosis." Doctoral thesis, Universitat de Barcelona, 2007. http://hdl.handle.net/10803/2227.
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The antiphospholipid syndrome (APS) is an acquired prothrombotic syndrome characterized by venous or arterial thromboses and pregnancy morbidity. It can present as primary APS without any discernable underlying disease, or in association with systemic autoimmune disease [usually systemic lupus erythematosus (SLE)], infections (mainly chronic viral infections) and malignant process, among others. It may also occur rapidly over days or weeks, when it is known as "catastrophic" APS (CAPS).The first study described one of the largest known cohorts of patients with primary APS from 4 different referral centers. The final study sample included 128 patients with primary APS with a median age of 42 years and mean follow-up of 9 years. After a median disease duration of 8.2 years, 110 (86%) patients remained with primary APS; 11 (8%) patients developed SLE; 6 (5%), LLD; and 1 (1%), myasthenia gravis. At the end of the study, 113 (88%) patients were alive and 15 (12%) patients had died. Our study confirms that progression from primary APS to SLE or LLD is unusual, even after a long follow-up.
In the second study, we evaluated 120 cases of antiphospholipid antibodies associated with malignancies with a mean age of 56 years, The main hematological malignancies found were B-cell lymphoma, spleen lymphoma and chronic myeloid leukemia. The main solid tumors were renal cell carcinoma, primary tumor of unknown origin, lung adenocarcinoma and breast carcinoma. Around one third of patients achieved aPL remission after treatment.
In the third study, we analyzed 15 cases of CAPS that appeared during pregnancy or the puerperium with a mean age at the time of the CAPS event of 27 years. In 7 of the 14 (50%) cases, CAPS appeared during pregnancy, in 6 (43%) cases it presented during puerperium and in 1 (7%) after curettage for a fetal death. The main clinical and serological characteristics were similar to those of patients with CAPS triggered by other factors, however we found some particular features including placental infarctions, pelvic vein thrombosis and myometrial thrombotic microangiopathy and HELLP syndrome.
Final conclusion: Primary APS is a widely recognized distinct entity which rarely progresses to SLE, even after long-term follow-up. APS may also be associated with other chronic disorders, such as solid tumors or hematological malignancies. In cases with the life-threatening variant of APS known as CAPS, pregnancy and the puerperium are periods of high susceptibility for the development of this often fatal form of presentation.
"SINDROME ANTIFOSFOLIPIDICO: EXPANDIENDO EL ESPECTRO CLÍNICA DE LA TROMBOSIS AUTOINMUNE"
El síndrome antifosfolipídico (SAF) es un síndrome protrombótico adquirido caracterizado por trombosis venosas y arteriales y pérdidas fetales recurrentes. Puede estar presente como SAF "primario" cuando no esta asociado a ninguna enfermedad autoinmune [fundamentalmente el lupus eritematoso sistémico (LES)] o en asociación a otros procesos tales como infecciones y procesos neoplásicos, entre otros. También puede manifestarse de una forma acelerada en días o semanas, caracterizado por trombosis de pequeños órganos y fallo multiorgánico, lo que se conoce como SAF "catastrófico".
En el primer estudio se analizó una de las series más amplia y con más largo seguimiento de pacientes con SAF primario. Se incluyeron 128 pacientes con un seguimiento medio de 9 años. Después de una duración media de la enfermedad de 8 años, 110 (86%) pacientes continúan con el diagnóstico de SAF primario, 11 (8%) pacientes desarrollaron un LES, 6 (5%) una forma incompleta de lupus ("lupus-like disease") y 1 (1%) paciente desarrolló una miastenia gravis. La presencia del test de Coombs positivo confiere un riesgo estadísticamente significativo para el desarrollo de LES. . Nuestro estudio confirma que es inusual que un SAF primario evolucione hacia un LES o una forma incompleta de lupus, incluso tras un período largo de seguimiento.
En el segundo estudio se incluyeron un total de 120 casos con anticuerpos antifosfolipídicos (AAF) asociados a procesos neoplásicos. Las principales neoplasias hematológicas relacionadas a los AAF fueron el linfoma de células B, el linfoma esplénico y la leucemia mieloide crónica. Los principales tumores sólidos fueron el carcinoma de células renales, los tumores de primario desconocido, el adenocarcinoma de pulmón y el cáncer de mama. Alrededor de una tercera parte de los paciente negativizaron los AAF después del tratamiento de la neoplasia.
En el tercer estudio se analizaron 15 pacientes con SAF catastrófico que ocurrieron durante el embarazo o el puerperio. Las características clínicas generales del SAF catastrófico durante el embarazo o el puerperio fueron similares a las del SAF catastrófico desencadenado por otros factores a excepción de una tasa mayor de abortos previos. Sin embargo se encontraron una serie de características particulares, como el síndrome de HELLP, la trombosis placentaria, la microangiopatía trombótica de miometrio o la trombosis de la vena pélvica.
CONCLUSIÓN FINAL: El SAF primario es una entidad propia ampliamente reconocida que en raras ocasiones evoluciona a un LES, incluso tras un período largo de seguimiento. El SAF puede asociarse a una serie de procesos crónicos como lo son las neoplasias hematológicas y los tumores sólidos. En aquellos casos con la variante "catastrófica" del SAF, el embarazo y el puerperio, constituyen un período de alta susceptibilidad para el desarrollo de esta variante altamente letal del SAF.
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Zhang, Yue. "Hemodynamic investigation and thrombosis modeling of intracranial aneurysms." Thesis, Lyon, INSA, 2015. http://www.theses.fr/2015ISAL0081/document.
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La sélection de variables est une tâche primordiale en fouille de données et apprentissage automatique. Il s’agit d’une problématique très bien connue par les deux communautés dans les contextes, supervisé et non-supervisé. Le contexte semi-supervisé est relativement récent et les travaux sont embryonnaires. Récemment, l’apprentissage automatique a bien été développé à partir des données partiellement labélisées. La sélection de variables est donc devenue plus importante dans le contexte semi-supervisé et plus adaptée aux applications réelles, où l’étiquetage des données est devenu plus couteux et difficile à obtenir. Dans cette thèse, nous présentons une étude centrée sur l’état de l’art du domaine de la sélection de variable en s’appuyant sur les méthodes qui opèrent en mode semi-supervisé par rapport à celles des deux contextes, supervisé et non-supervisé. Il s’agit de montrer le bon compromis entre la structure géométrique de la partie non labélisée des données et l’information supervisée de leur partie labélisée. Nous nous sommes particulièrement intéressés au «small labeled-sample problem» où l’écart est très important entre les deux parties qui constituent les donnéesFeature selection is an important task in data mining and machine learning processes. This task is well known in both supervised and unsupervised contexts. The semi-supervised feature selection is still under development and far from being mature. In general, machine learning has been well developed in order to deal with partially-labeled data. Thus, feature selection has obtained special importance in the semi-supervised context. It became more adapted with the real world applications where labeling process is costly to obtain. In this thesis, we present a literature review on semi-supervised feature selection, with regard to supervised and unsupervised contexts. The goal is to show the importance of compromising between the structure from unlabeled part of data, and the background information from their labeled part. In particular, we are interested in the so-called «small labeled-sample problem» where the difference between both data parts is very important
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Wahlgren, Carl Magnus. "Mechanisms of thrombosis and restenosis after vascular injury /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-260-8/.
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Smorenburg, Susanna Maria. "Heparins, cancer and thrombosis clinical and experimental studies /." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2000. http://dare.uva.nl/document/59625.
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Kunz, Gabriella. "Thrombomodulin gene mutations and their importance in thrombosis." Thesis, Imperial College London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248444.
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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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Mushunje, Alec. "Antithrombin conformational transitions and their implications in thrombosis." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620006.
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Bedredinova, V. O. "Absorbable stents for the treatment of vascular thrombosis." Thesis, Sumy State University, 2017. http://essuir.sumdu.edu.ua/handle/123456789/62808.
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Diseases of the heart and blood vessels - one of the leading causes of death and disability among the population all over the world. According to the World Health organization, cardiovascular disease is causes death of 16.7 million people per year. In Ukraine, during the last 15 years there has been increase in mortality in this pathology. In general the structure of mortality in Ukraine, cardiovascular diseases account for more than half. New technologies such as endovascular procedures and coronary artery shunting are becoming widely applied in Ukraine. The introduction of the new methods of myocardial revascularization expanded treatment options for patients with coronary artery diseases
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Howard, Adam Quentin. "The prevention of post-operative deep vein thrombosis." Thesis, Imperial College London, 2007. http://hdl.handle.net/10044/1/8187.
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Background: In a university hospital, disparate and unsatisfactory thromboprophylaxis in surgical patients was found. No hospital consensus was in place for the prevention of postoperative deep vein thrombosis (DVT). Literature review suggested low molecular weight heparin (LMWH) and anti-embolic stockings were the best prophylaxis, however the optimal length of stocking was unknown. Method: Audit of thromboprophylaxis in surgical patients and surgical doctors was performed. A randomised controlled trial investigated the efficacy and safety of a new single protocol of LMWH and the best length of stocking, for every patient requiring surgery under general anaesthesia. Of 426 patients interviewed, 376 were randomised into three stocking groups, Medi Thrombexin® Climax™ thigh-length, Thrombexin® Climax™ knee-length and Kendall TEDTM thigh-length. All patients received LMWH. DVT incidence was assessed by duplex ultrasonography. Complications of thromboprophylaxis were recorded. Compliance and health outcome measures were developed to assess patient stocking acceptability. Results: Audit revealed inadequate surgical thromboprophylaxis. A simple 'single protocol' improved doctors' thromboprophylaxis compliance on replicate audit. The randomised trial assessing the 'single protocol' showed no postoperative DVT occurred in the low or moderate-risk patients (n=85). Twenty-one DVT occurred in nineteen patients, all were high-risk patients (n=291): two with Thrombexin® Climax™ thigh-length stockings and eleven with Thrombexin® Climax™ kneelength (p
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Yamaji, Kyohei. "Bare-metal Stent Thrombosis and In-stent Neoatherosclerosis." Kyoto University, 2012. http://hdl.handle.net/2433/158059.
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Auwerda, J. J. A. "Acquired coagulation abnormalities and thrombosis in multiple myeloma." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2008. http://hdl.handle.net/1765/14217.
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Joshi, Smita. "CONTROLLING PLATELET SECRETION TO MODULATE HEMOSTASIS AND THROMBOSIS." UKnowledge, 2018. https://uknowledge.uky.edu/biochem_etds/37.
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Upon vascular injury, activated blood platelets fuse their granules to the plasma membrane and release cargo to regulate the vascular microenvironment, a dynamic process central to platelet function in many critical processes including hemostasis, thrombosis, immunity, wound healing, angiogenesis etc. This granule- plasma membrane fusion is mediated by a family of membrane proteins- Soluble N-ethyl maleimide Attachment Receptor Proteins(SNAREs). SNAREs that reside on vesicle (v-SNAREs) /Vesicle-Associated Membrane Proteins(VAMPs) interact with target/t-SNAREs forming a trans-bilayer complex that facilitates granule fusion. Though many components of exocytic machinery are identified, it is still not clear how it could be manipulated to prevent occlusive thrombosis without triggering bleeding. My work addresses this question by showing how the rates and extents of granule secretion could be regulated by various v-SNAREs. We also show that the granule cargo decondensation is an intermediate to secretion that also contributes to rates of cargo release.
Platelets contain four major VAMP isoforms (-2, -3, -7, and -8), however, VAMP-8 and -7 play a primary role while VAMP-2 and -3 are ancillary in secretion. To exploit this heterogeneity in VAMP usage, platelet-specific V-2/3-/- and V-2/3/8-/- mouse models were generated and characterized to understand how secretion influences hemostasis. We found that each VAMP isoform differentially contributes by altering the rates and extents of cargo release. The loss of VAMP-2 and -3 had a minimal impact while the loss of VAMP-2, -3 and -8 significantly reduced the granule secretion. Platelet activation and aggregation were not affected though the spreading was reduced in V-2/3/8-/- platelets indicating the importance of secretion in spreading. Though coagulation pathways were unaltered, PS exposure was reduced in both V-2/3-/- and V-2/3/8-/- platelets suggesting diminished procoagulant activity. In vivo experiments showed that V-2/3/8-/- animals bled profusely upon tail transaction and failed to form occlusive thrombus upon arterial injury while V-2/3-/- animals did not display any hemostatic deficiency. These data suggest that about 40-50% reduction in secretion provides protection against thrombosis without compromising hemostasis and beyond 50% secretion deficiency, the animals fail to form functional thrombi and exhibit severe bleeding. Additionally, detailed structural analysis of activated platelets suggests that the post-stimulation cargo dissolution depends on an agonist concentration and stimulation duration. This process is VAMP-dependent and represents intermediate steps leading to a full exodus of cargo. Moreover, we also show that VAMP-8 is important for compound fusion events and regulates fusion pore size.
This is a first comprehensive report that shows how manipulation of the exocytic machinery have an impact on secretion and ultimately on hemostasis. These animals will be instrumental in future investigations of platelet secretion in many other vascular processes.
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Olakareem, Halima. "Prognostic factors associated with the development of post-thrombotic syndrome after a deep vein thrombosis of the lower limb." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/7002/.
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Within 10 years of experiencing a deep vein thrombosis of the lower limb, up to 60% of people will be classed as suffering from post-thrombotic syndrome (PTS). The cause and risk factors for PTS are not well understood and there are no universally agreed diagnostic criteria. This thesis aimed to identify prognostic factors associated with developing PTS, the method(s) of diagnosing PTS and their relative reliability in identifying PTS. A systematic review of systematic reviews and a systematic review of primary studies was conducted to identify prognostic factors. Methods used to diagnose PTS were noted from these reviews. Prognostic factors from best evidence and methods of diagnosing PTS noted were presented to clinical experts for prioritisation via an e-Delphi study. Consensus was defined as ≥75% agreement. Fifty one potential prognostic factors and seventeen methods of diagnosing PTS were identified from the reviews and initial exploration of experts’ views. Experts reached consensus on eight prognostic factors and one method of diagnosing PTS. The prognostic factors identified can be considered for the development of a prognostic model, while the method of diagnosing PTS found to be most reliable from experts’ opinion should be considered when developing a reference standard for PTS diagnosis.
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Houwelingen, Adriana Cornelia van. "Fish against thrombosis? dietary fish and cardiovascular risk profile /." Maastricht : Maastricht : Rijksuniversiteit Limburg ; University Library, Maastricht University [Host], 1988. http://arno.unimaas.nl/show.cgi?fid=5411.
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Baarslag, Hendrik Jan. "Diagnosis and management of upper extremity deep vein thrombosis." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2003. http://dare.uva.nl/document/86567.
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Javed, Najma H. "Effects of lupus anticoagulants on thrombosis-related endothelial function." Virtual Press, 1987. http://liblink.bsu.edu/uhtbin/catkey/483176.
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Lupus anticoagulants (LA) have been identified as antiphospholipid antibodies which can alter certain membrane-related endothelial activities, resulting in increased thrombogenesis. The effects of LA-containing patient plasmas on selected thrombosis-related endothelial functions were examined; 68% of 25 patient plasmas exhibited significant antiphospholipid antibody (APA) IgG and/or IgM directed against one of the four phospholipids tested in vitro; 44% exhibited anti-endothelial antibody. Eighty percent of plasmas with anti-endothelial IgM exhibited APA reactive with phosphatidyl inositol; antiphospholipid IgG did not correlate well with antiendothelium IgG. Patient plasmas that significantly stimulated EC PGI2 secretion uniformly exhibited anti-phosphatidyl serine IgM.Multiple mechanisms of induction of LA, and strong association of anti-PS and anti-EC antibody with thrombosis and related disorders were observed.Ball State UniversityMuncie, IN 47306
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Williams, Christopher M. "Protein kinase Ca in bone eevelopment, thrombopoiesis and thrombosis." Thesis, University of Bristol, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.526061.
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Hitchcock, Jessica Ruth. "Regulation of hepatic inflammation and thrombosis during Salmonella infections." Thesis, University of Birmingham, 2014. http://etheses.bham.ac.uk//id/eprint/5119/.
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Salmonella typhimurium is one of the most common causes of bacteraemia in children in sub-Saharan Africa and is prevalent in HIV-infected individuals. However, symptoms of this systemic infection are unclear, and while fatalities are frequent, how infection kills is unknown. Here we use a mouse model of systemic (but resolving) infection to investigate physiological and immunological aspects of the host response to infection. The liver is colonised during systemic infection, and in the model used, bacterial numbers peak at day 7 and are largely resolved within a month. Inflammatory lesions, consisting of multiple leukocyte populations, develop within the liver. These persist and are more severe once bacterial clearance is established. Whilst lesions can develop in the absence of T and B cells, these cells contribute to the regulation of inflammatory foci. In the absence of interferon-γ, lesions do not develop and inflammation in the liver is largely absent. In parallel, extensive platelet thrombosis occurs in the liver venous system and the shared kinetics with lesion formation suggest these phenotypes may be co-regulated. Here we describe how parenchymal and vascular inflammation are anchored by inflammatory up-regulation of podoplanin expression in the liver. Thrombosis is substantially abrogated in the absence of C-like lectin-type receptor-2 (CLEC-2) expression on platelets and we show that podoplanin (the physiological ligand for CLEC-2) expression on clodronate-sensitive myeloid populations is necessary for thrombus development. Therefore, the parallel association between inflammation and platelet activation could be the basis for developing novel treatments for systemic bacterial infections in humans.
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Olsson, Eija. "Acute arterial thrombosis in microsurgery : clinical and experimental studies." Helsinki : University of Helsinki, 2001. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/olsson/.
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de, Wet Anna. "Incidence of Deep Vein Thrombosis in the Lower Extremity." Thesis, University of Sydney, 2020. https://hdl.handle.net/2123/23248.
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Venous thromboembolism (VTE) encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE).1,2 Factors such as venous stasis, vascular injury, hypercoagulability and major orthopaedic surgery such as hip/ knee replacement or hip fracture surgery increases the risk for thrombosis. Currently there is limited information on the incidence and risk of VTE following ankle fracture surgery and the economic impact on the use of prophylaxis for the prevention of VTE in these patients. Chapter one of this thesis provides a comprehensive literature review highlighting the epidemiology, risk factors, prophylactic modalities used and complications in both medical and surgical patients for the prevention of VTE. Chapter two is a retrospective study that examines this area, in particular, practice patterns in VTE prevention both in-hospital and beyond hospitalisation following ankle fracture surgery. These results showed that most of these patients received low molecular weight heparin (LMWH) and that the overall in-hospital VTE incidence was 2.9% (95% CI: 1.3 - 4.4). There was a 1.5-fold increase risk of VTE at three months post hospitalisation (4.3% (95% CI: 2.3 - 6.2), bleeding rates were low and there were no major complications. This led to a systematic literature review for chapter three evaluating the economic impact with use of pharmacological prophylaxis in major orthopaedic surgery for VTE prevention as well as complications and treatment costs. These results highlighted economic benefits with the use of LMWH compared to difference in healthcare systems. The first two chapters emphasise the importance of immobility for the risk of thrombosis. This is discussed in chapter four together with a summary of the main findings, gaps and future directions. The need to explore the importance of immobility on DVT risk led to a protocol development and ethics approval for the evaluation of the rates of DVT in diabetic foot ulcer patients with total contact casts.
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Simmonds, Rachel Elizabeth. "Protein S deficiency and familial thrombophilia." Thesis, Imperial College London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267993.
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Brown, Anthony James Moginie. "Studies of the molecular structures of the blood coagulation fibrinolytic proteins." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294268.
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Casa, Lauren D. C. "Role of von Willebrand factor in shear induced platelet accumulation in a microfluidic device." Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/53540.
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Thrombus formation under high fluid shear rates at the site of atherosclerotic plaque rupture leads to myocardial infarction and stroke. At high shear rates, thrombus is formed by platelets adhering via the glycoprotein von Willebrand factor (vWF). To investigate the relative contributions of vWF and platelets in high shear thrombosis, the present work developed a microfluidic thrombosis assay to meet low blood volume requirements and fluid shear conditions (3500-6000 s-1). Microfluidic conditions were selected to mimic the high shear environment of a diseased coronary artery, with the long-term objective of developing a clinically relevant assay for the assessment of thrombosis risk and treatment efficacy. The microfluidic design also addressed the requirement for volumetric thrombus formation rather than only surface platelet adhesion. As part of the design of the microfluidic assay, the effect of flow pulsatility on high shear thrombosis was investigated. It was found that steady wall shear rate matched to the mean pulsatile wall shear rate reproduced bulk thrombus formation characteristics of occlusion time, lag time, and thrombus growth rate, allowing subsequent experiments and future device design to utilize steady flow. The microfluidic assay was implemented to study the roles of vWF and platelets to thrombus formation using blood analogs produced from whole human blood diluted with normal saline at 90% and 99%. Hematocrit was restored to normal in all cases with the addition of red blood cells, and vWF and platelets were selectively restored to normal levels. Results showed that 90% dilutions with only vWF restored to normal levels occluded in 6/7 subject tested. The addition of platelets accelerated thrombus formation, but blood analogs with only platelets restored to normal levels occluded in only 2/5 subjects, indicating that vWF is more contributory in high shear occlusive thrombosis. At 99% dilutions, large thrombus formed with the addition of both platelets and vWF but was unstable and did not fully occlude the channel, indicating the possible requirement of an additional stabilizing factor(s) in occlusive thrombosis. Results of this study may lead to the development of improved anti-thrombotic treatments and improve patient care by providing a potential assay to evaluate treatment effectiveness and predict thrombosis risk.
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Kitchen, S. "Laboratory control of anticoagulant therapy : an analysis of current dilemmas; heparin." Thesis, University of Sheffield, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299588.
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Jamieson, Alec. "Assessment of fibrinolytic and antithrombotic activity resulting from modulation of endogenous fibrinolysis in animal models." Thesis, University of Aberdeen, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.358267.
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The primary aims of the project were: i) to develop assays capable of detecting changes in endogenous fibrinolytic activity for use in animal models. ii) to determine whether changes in endogenous fibrinolytic activity could be achieved following administration of a range of pharmacologically active agents. iii) to investigate the effect of such changes in endogenous fibrinolytic activity on thrombus formation and lysis in a suitable animal model in vivo. 1. Methods established for estimation of fibrinolytic activity in the plasma of rats and rabbit comprised chromogenic activity assays measuring tPA and PAI activity and the euglobulin clot lysis time assay as an index of fibrinolytic capacity. Changes in either plasma tPA or plasma PAI levels correlated well with changes in fibrinolytic activity as measured by the euglobulin clot lysis time assay; this comparison has previously not been carried out in animal studies. 2. A range of animal tests were investigated in an attempt to identify a paradigm of disease compromised fibrinolytic activity. Again, a systematic approach of this type had not previously been carried out in animals. The most significant alteration in plasma fibrinolytic activity was seen in the arthritic rabbit where levels of PAI and the acute phase reactant fibrinogen were significantly elevated. These data provide new evidence demonstrating PAI acting as an acute phase reactant in an animal model of inflammation. 3. Compounds were identified that either possessed pro-fibrinolytic actions (by elevating endogenous tPA activity or inhibiting endogenous PAI activity) or were shown to inhibit fibrinolytic activity (increased plasma PAI activity).
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Al-Hilali, Mahir Mohamad Ali. "Evaluation of plasminogen function in health and disease." Thesis, University of Southampton, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259938.
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Rhoné, Benoît. "Étude de la réactivité des uréthanes et polyuréthanes : application aux dispositifs médicaux." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066602/document.
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De nombreux dispositifs médicaux implantables sont utilisés chaque jour. Le contrôle de l'interface du dispositif avec les tissus vivants environnants doit encore être amélioré. De nombreux dispositifs médicaux implantés dans le corps sont le siège d’une ou plusieurs complications graves, telles que l'infection ou la thrombose. C’est notamment le cas des cathéters intraveineux. Dans ce contexte, nous avons cherché à développer une stratégie permettant de réduire les complications associées à leur utilisation, via l’immobilisation covalente de polymères sur les matériaux utilisés en implantation (polyuréthane). La réactivité des uréthanes a d’abord été étudiée, permettant d’identifier la réaction de transcarbamoylation comme outil efficace de modification des uréthanes et polyuréthanes en conditions douces. La réaction entre des poly(éthylène glycol) et la surface de polyuréthane, catalysée par des bases, a permis de rendre les surfaces de PU hydrophiles. Les conditions de modification ont été optimisées. Les surfaces ont été analysées: angle de contact, spectrométrie infrarouge, XPS et TOF-SIMS. Les surfaces modifiées ont montrées d’excellentes propriétés antiadhésives avec une diminution significative de l’adsorption protéique, de l’adhésion de cellules, de plaquettes et de bactéries. Les propriétés des surfaces modifiées ont été évaluées et comparées à d’autres systèmes. Cette stratégie est prometteuse pour la modification en une étape de surfaces de polyuréthane. Les tests in vitro montrent le potentiel de cette modification de surface pour obtenir un polyuréthane ayant une biocompatibilité accrueMany implantable medical devices (stents, catheters, cardiac valves…) are used everyday in many domains. The control of the interface between the medical device and the surrounding tissue is still to be improved. Many implanted devices are facing serious complications following implantation such as infections or thrombosis. These problematics are especially present for intravenous catheters used to administrate drugs. In this context, we investigated a way to strongly limit the problematics associated with their implantation, by covalently binding polymers at the surface, to reduce protein adsorption and cell adhesion on the materials used in implantation (polyurethane). The reactivity of urethanes was first studied, it allowed identifying the transcarbamoylation reaction as an efficient tool to modify urethanes and polyurethanes in soft reaction conditions. The reaction of poly (ethylene glycol) and the polyurethane surface, catalyzed by bases, allowed us to get hydrophilic polyurethane surfaces. Modification conditions were optimized to obtain a good covering of the surface with PEG. Surfaces were analyzed: contact angle, profilometry, infrared spectroscopy, XPS and TOF-SIMS. Modified surfaces showed excellent antiadhesive properties with a strong reduction of protein adsorption, cell and bacterial adhesion. The properties of modified surfaces were evaluated and compared to other systems. This strategy of modification is promising to allow one step modification of polyurethane surfaces. In vitro tests show the potential of this surface modification technique to obtain a polyurethane with enhance biocompatibility
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MacMeccan, Robert Miles III. "Mechanistic Effects of Erythrocytes on Platelet Deposition in Coronary Thrombosis." Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/19786.
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A new lattice-Boltzmann finite-element method is used to simulate large numbers of deformable red blood cells and platelets in suspension for the investigation of stress-mediated platelet-deposition mechanisms in blood. The coupled lattice-Boltzmann finite-element method provides the novel ability to simulate hundreds of realistic and deformable red blood cells and produce continuum-scale physics at physiologic hematocrit and low arterial-shear rates. The new method is developed and shown to produce single red blood cell deformation consistent with experimental results in flow chambers. Simulations of 77 to 216 cells in unbounded shear flow produce bulk and micro-rheological behavior consistent with experimental results in viscometers and tubes, including shear-thinning behavior at various shear rates. Investigation of the local stress environment in blood indicates that, although the majority of platelets experience a time-averaged shear stress equal to the suspension stress, 25% of platelets experience a localized shear stress greater than twice the suspension stress.
The lattice-Boltzmann finite-element method developed in this work has been shown capable of investigating the fundamental gap between cell-level processes and continuum-level function. The complex stress environment in whole blood has been described for simple shear flow and the methodology may be extended to more complex flow geometries and incorporate platelet-adhesion models for adhesion studies. Thus, this research fits into the greater objective of prediction and control of platelet deposition in clinical and engineering applications. Furthermore, the ability to bridge the gap between cell-level processes and continuum-level function is useful in other important cardiovascular areas including leukocyte adhesion, platelet aggregate embolization, and artheriogenesis.
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Lane, I. F. "The relationship between platelet-vessel wall interaction thrombosis and atherosclerosis." Thesis, University of Oxford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233551.
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Harrison, Sarah Elinor. "The use of the lattice Boltzmann method in thrombosis modelling." Thesis, University of Sheffield, 2007. http://etheses.whiterose.ac.uk/14507/.
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The effects of thrombosis greatly contribute to the incidence of mortality in the Western World. Understanding thrombosis is therefore crucial in providing the correct treatment for the underlying pathologies. Numerical methods have previously been used to investigate various factors associated with thrombosis, usually starting from solutions of the Navier-Stokes equations. This thesis presents the development and implementation of models of thrombosis using the lattice Boltzmann method, which is a relatively new technique for simulating fluid dynamics. The advantages and disadvantages of this methodology are critically reviewed and two major pathologies, atherosclerosis and deep vein thrombosis have been chosen to demonstrate principles of the application. The first part of the work concentrates on the simulation of flow and clotting in idealised stenotic occlusions representative of the geometry and flow conditions in a diseased human femoral artery. Simulations of unsteady flow are reported and comparisons are made to previous flow visualisation studies. Stability issues regarding the diffusion algorithm are investigated in detail. In the first instance, clotting is simulated with the use of an aging model with extensions including proximity and shear stress. Comparisons are made with experimental results obtained using milk as a blood analogue. )'he second part of the work focuses on increasing the complexity of the models to incorporate the representations of the actions and distribution of the platelets, proteins and enzymes involved in the coagulation cascade. The models are tested in 2D geometries to demonstrate their functionality. As an example of this work, a model of deep vein thrombosis was developed, based on a hypothesis supported by the clinical literature. The foundations laid in this project allow for future developments, which will incorporate further details of thrombotic processes, in the hope that a valuable predictor of thrombosis can be developed.
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Hume, Struan. "Pulsatile Flow in Computational Modelling of Thrombosis in Cerebral Aneurysms." Master's thesis, Faculty of Health Sciences, 2019. http://hdl.handle.net/11427/31581.
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Ngoepe and Ventikos have developed one of a growing number of computational models of thrombosis of cerebral aneurysms designed with consideration towards clinical use and research. Their model, amongst many others, utilizes computationally inexpensive steady flow conditions. However, pulsatile flow better characterizes blood flow in-vivo. Steady flow is an acceptable approximation of pulsatile flow from a fluid dynamics perspective, but there is no prior evidence suggesting whether it is an acceptable approximation when considering clot formation within a flowing environment. To this end a pulsatile flow model has been created in ANSYS® Fluent, and a function from Ngoepe and Ventikos’s computational model that simulates the release of thrombin, a chemical responsible for clotting activation, has been implemented. The output of this simulation is compared to the output of an otherwise identical simulation utilizing Particle-Image-Velocimetry (PIV) validated steady flow conditions, to determine whether clotting outcome of Ngoepe and Ventikos’s model, amongst others, differs with pulsatile flow This experiment revealed that the concentration of thrombin required for clotting activation is generated in nearly half the time when utilizing pulsatile flow over steady flow. Pulsatile flow creates unsteady flow patterns within the aneurysm, which create an environment where less thrombin is carried out of the aneurysm and into the regular bloodstream. This indicates that steady flow approximations for realistic clotting in computational models of thrombosis of cerebral aneurysms without strong consideration for the effects of pulsatile flow are inaccurate.