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1
Auger, Martin J. "Haemostasis and cancer." Thesis, University of Liverpool, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.329371.
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2
Faughan, Marian. "Copper and haemostasis." Thesis, University of Ulster, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284849.
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3
Davidson, Colin John. "Molecular evolution of haemostasis." Thesis, Imperial College London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368908.
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4
Faxälv, Lars. "Imaging methods for haemostasis research." Doctoral thesis, Linköpings universitet, Klinisk kemi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-19178.
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Blood is a vital part of the human physiology; a transport system that brings nutrients and oxygen to sustain living cells and simultaneously facilitates the removal of carbon dioxide and other waste products from the body. To assure the continuity of these functions, it is of uttermost importance to keep the flowing blood inside the vascular system at any cost. The principal components of the haemostatic system are the blood platelets and the plasma coagulation system, both working in concert to create a blood stopping haemostatic plug when a vessel is ruptured. In modern health care, methods for treatment and diagnostics often implicate the contact between blood and artificial materials (biomaterials). Biomaterial surfaces may activate platelets and the coagulation cascade by exposing a surface that during blood contact shares certain characteristics with surfaces found at the site of vascular injury. Therefore it is of great importance that the mechanisms behind the interactions between foreign surfaces and blood are studied in order to minimize, and if possible, prevent unnecessary reactions that may lead to thrombosis. This thesis describes two important methods to study blood – surface interactions in terms of surface induced plasma coagulation and platelet adhesion/aggregation. The method ‘Imaging of coagulation’, a coagulation assay based on time-lapse image capture of the coagulation process was developed during the course of this work. The use of images enables the method to answer questions regarding where coagulation was initiated and how fast coagulation propagates. Such questions are highly relevant in the study of blood-biomaterial interactions but also in general haemostasis research. In vivo, platelet adhesion and aggregation are events that always proceed under flow conditions. Therefore we also developed a cone-and-plate flow model to study these mechanisms under similar conditions in vitro. The cone-and-plate setup was found to be a flexible platform and was used for both blood compatibility testing of potential biomaterials as well as for general haemostasis research. With the above mentioned methods we tested the haemocompatibility of glycerol monooleate (GMO), a proposed substance for use in biomaterial applications. It was found that GMO did not activate coagulation to any great extent either in plasma or in whole blood. Surface induced coagulation and platelet adhesion was also studied on PEG-containing hydrogels and compared with hydrogels constructed from three different non-PEG-containing monomers. It was concluded that all the grafted hydrogels, in particular those produced from the monomers 2-hydroxyethyl methacrylate (HEMA) and/or PEG- methacrylate (PEGMA), demonstrated good haemocompatibility. Supported phospholipid bilayers were used to investigate the relationship between surface charge and procoagulant activity. The coagulation process was studied in a straightforward manner using the imaging of coagulation setup. We concluded that the content of negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-L-serine] (POPS) in the bilayer must exceed ~ 6% for the bilayer to exert procoagulant activity. The physiological role of factor XII in human haemostasis and thrombosis was investigated in the imaging of coagulation setup and the cone and plate setup by the use of surfaces with thrombogenic coatings. We found that tissue factor initiated coagulation could be greatly accelerated by the presence of contact activating agents in a platelet dependent manner. In conclusion, the method ‘Imaging of coagulation’ and platelet adhesion/aggregation in the cone-and-plate flow model are both versatile methods with many possible applications. The combination of the two methods provides a solid foundation for biomaterial and haemostasis research.
5
Turkington, Philip Thomas. "The role of polymorphonuclear proteinases in haemostasis." Thesis, Queen's University Belfast, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317075.
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6
Holmes, Valerie Anne. "Early markers of haemostasis in normal pregnancy." Thesis, University of Ulster, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274405.
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7
McLellan, David Sinclair. "Factor VIII in health and disease - the relationship of VIII procoagulant (VIII:C) to VIII procoagulant antigen (VIII:CAg) in selected states." Thesis, Brunel University, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.280711.
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8
Hardy, Elaine. "Novel approaches to inhibition of platelet behaviour in pre-eclampsia." Thesis, University of Nottingham, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282831.
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9
Forster, Trevor Henry. "Effect of inhibitors of platelet function in haemostasis." Thesis, Queensland University of Technology, 1986. https://eprints.qut.edu.au/36709/1/36709_Forster_1986.pdf.
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Investigation of the role of platelets in the haemostatic
process has been a high priority for many years. In
spite of this the mechanisms by which platelets help to
maintain vascular integrity in undamaged blood vessels
have not been clearly defined. The concept of
endothelial support suggested by the work of Wojcik, Van
Horn, Webber and Johnson (6) has been controversial as it
implies a direct interaction between platelets and
endothelium. An alternate theory offered has been that
of platelet support by attachment to sub-endothelium
following damage to the endothelial cell layer.
To investigate the proposition that platelets and
endothelial cells were capable of direct interaction, a
reaction system using cultured human umbilical vein
endothelial cells was devised. As a result of
experiments using this model it has been shown that a
direct reaction between platelets and endothelial cells
does occur in vitro.
Experiments and techniques were devised to investigate
both the observed interaction and to assess the effect of
inhibitors of platelet function on the reaction.
Evidence gained by scanning electron microscopy and
transmission electron microscopy indicates that a
specific interaction actively involving endothelial cells
is responsible for the observed attachment of platelets
to these cells.
Studies using aspirin inhibited platelets indicate that a
two stage process is involved
first stage of which is
cyclo-oxygenase pathway. The
in this interaction,
independent of
second stage of
reaction appears to involve an active contribution
endothelial cells via their cyclo-oxygenase pathway.
10
Mackie, Eileen Elizabeth. "Exercise and haemostasis in health and ischaemic heart disease." Thesis, University of Glasgow, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433574.
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11
Sydorchuk, R. I. "Еarly postoperative changes of primary haemostasis under abdominal sepsis." Thesis, БДМУ, 2022. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/19685.
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12
Milne, Alan Anderson. "Coagulopathy and haemostasis in surgery for abdominal aortic aneurysm." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/21422.
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Coagulation studies were performed in a series of 24 patients with asymptomatic abdominal aortic aneurysm. Levels of fibrinogen were high but within the normal range, and there was no evidence of systemic activation of the soluble coagulation or fibrinolytic systems. Coagulation studies were performed in a series of six patients undergoing elective aortic aneurysm repair. It was found that thrombin, fibrinolytic and platelet activation increases during the period of initial dissection in a time dependent manner. After the administration of heparin and the application of the aortic cross clamp, thrombin, fibrinolytic and platelet activation reduced. After reperfusion there was an increase in platelet activation which correlated with the duration of cross-clamping. Coagulation studies were performed in a series of 22 patients presenting with ruptured aortic aneurysm. At time of admission there was marked activation of platelets and thrombin in all patients which increased greatly by the end of operation. Platelet count at the end of operation was significantly lower in patients who died than in survivors. Samples of subcutaneous fat and skeletal muscle were taken at the start of operation in six patients with ruptured aneurysm. Transmission electron microscopy was used to examine the endothelial cells in small vessels in these samples. When compared with samples from six control patients undergoing elective aortic surgery it was found that there were significant ultrastructural differences in the endothelial cells from patients with rupture. A randomised controlled study of fibrin sealant as a topical haemostatic agent at vascular anastomoses was carried out in 57 patients undergoing aortic aneurysm repair, carotid endarterectomy or arterial bypass graft using polytetrafluoroethylene bypass graft. The time taken to achieve haemostasis at the anastomoses was significantly reduced in patients treated with fibrin sealant. The reduction was most marked in patients undergoing carotid endarterectomy.
13
McWilliam, Nicola A. "The fibrinolytic system of human bone marrow." Thesis, University of Aberdeen, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337476.
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The fibrinolytic system of normal and leukaemic bone marrow was examined. Normal bone marrow had a very active fibrinolytic system due to abundant free t-PA, with negligible contribution from u-PA. High levels of PAI-2 antigen were observed in addition to PAI-1. Plasminogen, the precursor of plasmin was detected, mainly in complex with α2-AP, indicating that plasmin had been generated. The balance of the fibrinolytic system in normal bone marrow contrasted with the system in plasma, where plasmin is not normally generated. In bone marrow the t-PA level was greater than that of the inhibitors while in plasma t-PA circulates in complex with PAI-1. t-PA, u-PA, u-PAR, PAI-1 and PAI-2 were localised to cells of the myeloid, monocytic, megakaryocytic and T-lymphoid lineages in normal marrow. In contrast, cells of the B-lymphoid lineage did not possess the antigens of interest. In addition, non-haematopoietic cells in the marrow were examined, and it was observed that osteocytes, endothelial cells, smooth muscle cells and adipocytes contained the antigens of the fibrinolytic system. PAI-1, PAI-2, u-PA, u-PAR and probably t-PA were synthesised by the cells of the marrow, while plasminogen and α2-AP arose from the general circulation. The activity and antigen levels of the components of the fibrinolytic system differed between normal and leukaemic bone marrow. In leukaemic marrow, u-PA was observed, while t-PA and PAI-2 were decreased compared with normal bone marrow. PAI-1, plasminogen, α2-AP and plasmin-α2-AP complex were similar to normal bone marrow. The appearance of u-PA was probably associated with the malignant phenotype and may confer an invasive advantage on the leukaemic cell. In addition, the profile of the fibrinolytic system observed in leukaemic bone marrow may contribute to the haemorrhagic symptoms associated with certain forms of leukaemia.
14
Amirkhosravi, Mohammadali. "Procoagulant activity of the MC28 fibrosarcoma in vitro and in vivo : its role in metastasis." Thesis, University of Southampton, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.339478.
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15
Evans, Phillip Adrian. "The clinical and laboratory effects of intravenous fluids on haemostasis." Thesis, University of Leicester, 2003. http://hdl.handle.net/2381/29428.
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The intravenous administration of fluids in shock is life saving. However, there is increasing controversy as to the rationale for the normalisation of blood pressure in the treatment of shock with either colloids or crystalloids. Increasing the blood pressure by either the administration of colloids or crystalloids may also impair the formation of new blood clots and also dislodge existing ones and thus contribute to ongoing haemorrhage. The main aim of this thesis was to investigate the intrinsic and volumetric effect that these different intravenous resuscitation fluids have on the haemostatic process and bleeding. A variety of studies including in vitro mechanistic investigations, electron microscopy, randomised trials, randomised and double blinded trials were carried out. These were supported by epidemiological and systematic literature reviews to clarify the controversy.
16
Segal, Helen Cheryl. "The effect of aprotinin on haemostasis during orthotopic liver transplantation." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405146.
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17
Loots, Deirdré. "The effects of vitamin C on the haemostatic system / Deirdré Loots." Thesis, North-West University, 2003. http://hdl.handle.net/10394/207.
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Motivation:
Cardiovascular disease (CVD) is one of the leading causes of mortality and morbidity in South
Africa and worldwide. Dyslipidaemia and an increased coagulation state contribute to the
development of CVD. The quality of fibrin network structure (FNS) may also contribute to the
risk for CVD and thrombosis. Changes in fibrinogen concentration directly affect FNS.
Management of these risk factors is important and dietary intervention forms an essential part of
this management program. An increased intake of vitamin C can lead to a decreased
susceptibility to infection and subsequently to decreased levels of haemostatic factors (that give
rise to an anti-thrombotic state) and thus reduction in CVD and mortality. Furthermore, vitamin
C may prove to be beneficial by increasing the pro-fibrinolytx activities of FNS (formation of
thick fibrin fibers and more lysable clots) that could result in a reduction in atherosclerosis and
subsequent CVD.
Obiective:
To investigate the effects of FoodState Vitamin C complex supplementation on haemostatic
factors, FNS, serum lipids and lipoprotein (a) (Lp(a)) in hyperlipideamic adults.
Methods:
Thirty free-living hiperlipidaemic volunteers from the Lipid Clinic, Potchefstroom University for
Christian Higher Education (CHE), participated in this randomised placebo controlled double
blind crossover study. The subjects were randomly divided into two groups (A or B). After a
run-in period of 4 weeks during which the subjects excluded all vitamin supplements, Group A
received 2 tablets/day of FoodState Vitamin C complex (500mg vitamin C, 600mg magnesium
food complex, 900mg vitamin B complex and 160mg bioflavonoids) and Group B received 2
tablets/day of placebo, for at least 8 weeks. A washout period of 8 weeks followed after which
the treatments were crossed-over for a further 8 weeks. Fasting blood samples were drawn 8
times (two samples, one week apart at the beginning and end of each treatment).
Results:
FoodState Vitamin C complex supplementation did not significantly influence the levels of
plasma fibrinogen, plasminogen activator inhibitor 1 activity (PAI-I act), tissue plasminogen
activator antigen (tPA ag) or d-dimer. Serum lipids and Lp(a) were also not affected. Median
plasmin-antiplasmin complex (PAP) and thrombin-antithrombin complex (TAT) levels, which are
markers of plasmin (initiate fibrinolysis) and thrombin (initiate coagulation) generation
respectively, were both significantly decreased compared to placebo (PAP: 4.05[-23.39,
-0.231% vs 1.81[-8.95, 8.091%; TAT: -5.81[-18,47, 0.391% vs 0.12[-8.03, 13.51%). FoodState
Vitamin C complex beneficially affected FNS by significantly increasing compaction
(49.95[47.55,53.70]% to 51.85[48.55,56.65]%).
Conclusion:
The decreases in TAT and PAP are possibly an indication that the FoodState Vitamin C
complex decreased the initiation of haemostasis, which in turn led to a compensatory reduction
in fibrinolysis. FoodState Vitamin C complex may, therefore be protective of cardiovascular
disease by causing a new reduced steady state of hemostatic balance and more lysable clots
(increased compaction).Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2004.
18
Börsch-Haubold, Angelika Gabriele. "Regulation of cytosolic phospholipase Aâ†2 in human platelets by Ca'2'+ and phosphorylation." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337558.
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19
Scott, Nigel T. "Investigations on human factor 8 and platelet function." Thesis, University of East London, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.353257.
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20
Donders, Servaes Hubert Joan. "Correlations between haemostasis parameters and several cardiovascular risk factors in man." [Maastricht : Maastricht : Rijksuniversiteit Limburg] ; University Library, Maastricht University [Host], 1992. http://arno.unimaas.nl/show.cgi?fid=5696.
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21
Fall, Lewis. "Redox regulation of haemostasis : modulation by inspiratory hypoxia and physical exercise." Thesis, University of South Wales, 2012. https://pure.southwales.ac.uk/en/studentthesis/redox-regulation-of-haemostasis-modulation-by-inspiratory-hypoxia-and-physical-exercise(712686ec-639c-4d2f-b779-47e1b3b21da1).html.
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Introduction: Haemostasis is the arrest of bleeding. In recent years, in-vitro studies have suggested that secondary haemostasis (blood coagulation) is subject to activation by reactive oxygen species (ROS). It is known that patients who suffer from vascular disease are typically hypoxaemic and in the case of peripheral occlusive artery disease (POAD), physical exercise is used to improve symptom free mobility in the affected limbs. Hypoxia and physical exercise are two potent independent and synergistic initiators of ROS. We identified a clear need for in-vivo analysis of this novel area of research. Aims: There were two main aims of this research. 1. To explore the in-vivo influences of inspiratory hypoxia and physical exercise on biomarkers of haemostasis; and in doing so and subsequently carry out a randomised double blind placebo control trial to explore the interaction between oxidative stress (ROS accumulation) and haemostasis. Hypothesis: It was hypothesised that hypoxia and exercise would be independently and synergistically associated with an increase in oxidative stress, resulting in coagulation activation. We hypothesised that intervention with free radical reaction-chain breaking antioxidant vitamins would attenuate oxidative stress and thus attenuate the activation of coagulation. Methods: study 1 - Healthy males were subjected to six hours of normobaric hypoxia (12% inspired oxygen) and then a physical exercise challenge to exhaustion (cycling ramp-test). Citrated plasma was collected pre hypoxic exposure, post six hours of exposure, then immediately post exercise and analysed for routine clinical markers of coagulation (aPTT, PT, TT and fibrinogen) and analysed with and without correction for plasma volume shift. Data were analysed using a one-factor repeated measures ANOVA incorporating one within (condition: time point) subjects factor. Following a significant main effect and interaction, paired samples t-tests were employed to make post hoc comparisons at each level of the within-subjects factor. Study! - Healthy males were subjected to a double blind, randomised, placebo controlled intervention with vitamin C (a water soluble) and vitamin E (a lipid soluble), two ROS-scavenging, chain breaking antioxidants. The intervention lasted eight weeks to insure membrane enrichment with antioxidants. The methods of study one were repeated but with a pre-intervention time point added and the addition of two extra markers of thrombin generation (PF1+2 and T-AT). Data were analysed using a two-factor mixed ANOVA incorporating one between (group: antioxidant intervention vs. placebo control) and one within (condition: time point) subjects factor. Following a significant main effect and interaction, a paired samples t-test was used to make post hoc comparisons at each level of the within-subjects factor, with the alpha level Bonferroni corrected for multiple comparisons Between-group comparisons were assessed using independent samples t-tcsts applied to each level of the between-subjects factor. Results: Study 1 - Hypoxia was not associated with activation of coagulation. Physical exercise increased the activity of contact factor coagulation pathway activation. Study 2 - The intervention increased thrombin generation in the antioxidant group. This was met with an antagonistic antithrombin activation. Hypoxia did not impact the placebo group, but normalised the thrombin generation of the antioxidant group. Physical exercise increased contact factor pathway (CFP) as per study 1, but thrombin generation was unaltered. Hypoxia suppressed fibrinolysis post exercise, which is known to be activated in normoxic exercise. Discussion: hi study one, hypoxia alone did not activate coagulation. We hypothesised that this could be tentative evidence of a ROS concentration threshold for activation since once exercise was superimposed the accumulation of ROS activated the CFP. Correction for changes in plasma volume nullified the increased activity of the CFP. Corrections for shifts in plasma volume are routinely ignored in the literature and this was a novel finding. Study 2 was the first intervention of its kind. The increase in thrombin generation pre-post intervention with antioxidants suggests compelling evidence of in-vivo regulation of coagulation by ROS. But the direction of change was completely contrary to the original hypothesis. The confirmation that hypoxia does not activate coagulation is important, especially given the controversy surrounding long-haul flight deep vein thrombosis. Interestingly, exercise did not increase thrombin generation, despite the increase in the CFP. These findings suggest haemostasis is indeed subject to control by the body's redox state invivo via an as of yet, unknown mechanism.
22
Hornsey, Valerie Scott. "Studies on monoclonal antibodies to Von Willebrand factor and coagulation factor VIII." Thesis, Heriot-Watt University, 1988. http://hdl.handle.net/10399/972.
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Lin, Xia. "The effect of exercise and alcohol ingestion on blood coagulation, fibrinolysis and lipid profiles." Thesis, Liverpool John Moores University, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388585.
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24
Smith, Felicity Barbara. "Role of fibrinogen and fibrin D-dimer in peripheral arterial disease." Thesis, University of Glasgow, 1998. http://theses.gla.ac.uk/30947/.
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This thesis is composed of two studies. The principal aim of the first study, the Sites of Atheroma Study, was to determine whether plasma fibrinogen, fibrin D-dimer and other haemostatic factors (von Willebrand Factor and plasminogen activator inhibitor - type I) were related to the angiographic site and severity of atherosclerosis in the arteries of the lower limb. The principal aim of the second study, the Prognostic Study of Intermittent Claudication, was to determine whether plasma fibrinogen, fibrin D-dimer and other haemostatic factors (von Willebrand Factor and tissue plasminogen activator), were related to the future incidence of atherothrombotic events, and deterioration of peripheral arterial disease in subjects with intermittent claudication. The study samples in both studies consisted of men and women with ischaemic symptoms in the lower limb referred to the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. In the Sites of Atheroma Study, 192 patients referred for angiography were categorised by site and severity of peripheral atherosclerosis using the Bollinger angiographic scoring system. A clinical examination was conducted on each patient including the administration of a questionnaire and taking of a blood sample for the measurement of haemostatic factors. In the Prognostic Study, 607 patients with intermittent claudication who had had a comprehensive examination at baseline, including measurement of haemostatic factors, were followed up over six years to determine the incidence of fatal and non-fatal ischaemic heart disease and stroke and deterioration of peripheral arterial disease. Follow-up data were obtained from hospital records, general practitioners, self-administered questionnaires, the Information and Statistics division of the Common Services Agency and the Scottish National Health Service Central Registry. Results from the Sites of Atheroma Study indicated that 34 (17.7%) patients had predominantly aorto-iliac disease, 85 (44.3%) had femoro-popliteal disease and 73 (38.0%) had dual-site disease. There were no significant differences in the mean levels of the haemostatic factors between patients with disease affecting different sites. An independent relationship was found between nephelometric fibrinogen and between fibrin D-dimer and disease severity only in the femoro-popliteal arteries. On multiple regression, fibrinogen remained independently associated with disease severity in the femoro-popliteal arteries, when life-time smoking or current smoking were taken into account. There was no influence of current smoking on the association between fibrin D-dimer and disease severity but, on inclusion of life-time smoking, the association became non-significant. In the Prognostic Study of Intermittent Claudication, a total of 210 (34.6%) patients died during the six year follow-up period. Of these 90 (42.9%) died from ischaemic heart disease, 29 (13.8%) from stroke and 27 (12.9%) from other vascular causes, including cardiac arrhythmias and ruptured aneurysm. Ninety three (15.3%) patients had a non-fatal myocardial infarction and 79 (13.0%) had a fatal or non-fatal stroke. Forty five (7.4%) patients underwent investigations for peripheral arterial disease and 64 (10.5%) patients progressed to severe chronic leg ischaemia. A total of 203 (33.4%) patients did not have a vascular event or show any deterioration of limb ischaemia. Baseline median levels of plasma fibrinogen, fibrin D-dimer and von Willebrand Factor were significantly higher in patients who died from ischaemic heart disease compared to those who had no vascular events. Tissue plasminogen activator antigen levels were significantly elevated in patients who suffered a stroke. All the relationships between the haemostatic factors and vascular events became weaker and statistically non-significant in analysis adjusting for cardiovascular risk factors and baseline ischaemic heart disease. von Willebrand Factor levels were significantly raised in claudicants who developed severe chronic leg ischaemia (rest pain, ulceration and gangrene). In multivariate analyses adjusting for life-time smoking, fibrinogen became significantly associated with the risk of vascular intervention, and von Willebrand Factor was associated with the risk of severe chronic leg ischaemia. In conclusion, these results indicate that there may be a stronger relationship between chronic smoking and increased fibrin turnover than coagulation in symptomatic peripheral arterial disease. Increased coagulation and fibrinolytic activity may also contribute to thrombosis or progression of atherosclerosis in the coronary and cerebral arteries in claudicants. The effect that fibrinogen, fibrin D-dimer and other haemostatic factors may have on the progression of peripheral arterial disease was mostly independent of cigarette smoking.
25
Tzoulaki, Ioanna. "Inflammation and haemostasis in the development and progression of peripheral atherosclerotic disease." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/2148.
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Peripheral arterial disease (PAD) defines atherosclerotic disease of the arteries to the legs. PAD begins early in life and remains asymptomatic over long periods. The ankle brachial index (ABI) is an important diagnostic test which can identify asymptomatic individuals and serve as a good marker of the underlying peripheral and systemic atherosclerosis. Recent advances in vascular biology proposed a role of inflammatory and haemostatic mechanisms in atherosclerotic disease. Although inflammatory and haemostatic markers have been associated with coronary atherosclerosis in large scale epidemiological studies their role in PAD development is not well established and for many markers unknown. Also, their relationship with the progression of early asymptomatic disease has not been studied before. The aim of this thesis was to examine 12 markers of inflammation and haemostasis in relation to peripheral atherosclerotic progression and incident PAD. The Edinburgh Artery Study was used for this analysis. This is a population based cohort study of 1,592 men and women recruited in 1987. ABI was measured at baseline and at two follow up examinations which were conducted after 5 and after 12 years. Also, subjects were followed up for cardiovascular events for 17 years. Conventional cardiovascular risk factors, C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin, fibrinogen, D-dimer, tissue plasminogen activator (t-PA), vonWillebrand factor (vWF), factor VII, fibrinopeptide A (FpA) and prothrombin fragments 1+2 (F1+2) were measured at baseline. Valid ABI measurements were available for 1,582 subjects at baseline, for 1,081 subjects at the 5 year follow up and for 816 subjects at the 12 year follow up. The population showed a progression in atherosclerotic disease assessed by the mean ABI decline over time. The mean change in ABI was -0.04 (0.18) after 5 years and -0.06 (0.19) after 12 years. From inflammatory markers, CRP (p <0.01), IL-6 (p <0.001) and ICAM-1 (p <0.01) were associated with atherosclerotic progression after 12 years, independently of baseline ABI and of conventional cardiovascular risk factors. Also, from haemostatic markers, fibrinogen (p =0.05) and D-dimer (p ≤ 0.05) were significantly associated with atherosclerotic progression independently of baseline ABI and cardiovascular risk factors. Moreover, subjects with higher levels of both D-dimer and IL-6 at baseline had the greatest ABI decline. Also, IL-6 showed the stronger independent effect on atherosclerotic progression and retained statistical significance after adjustments for all inflammatory markers and for fibrinogen and D-dimer. Approximately 26% of the baseline population developed at least one event of major CVD and 14% of the baseline population developed symptomatic PAD after 17 years of follow up. Inflammatory markers, CRP and IL-6 showed modest associations with PAD which lost statistical significance in the multivariable model. On the other hand, these markers were associated with incident major CVD with hazard ratios (95% CI) 1.6 (1.2, 2.3) and 1.8 (1.3, 2.6) respectively (top vs. bottom tertile) in the multivariable model. ICAM-1 showed weak associations with incident CVD, however, was significantly associated with PAD with hazard ratio (95% CI) 1.8 (1.2, 2.7) (top vs. bottom tertile) after adjustments for cardiovascular risk factors and CVD at baseline. Haemostatic markers, fibrinogen and D-dimer were associated with 2.2 (95% CI: 1.5, 3.2) and 1.7 (1.2, 2.6) increase in the risk of PAD development and 1.8 (1.3, 2.3) and 1.6 (1.2, 2.1) increase in the risk of CVD independently of cardiovascular risk factors and history of CVD at baseline, respectively. This analysis showed a major role of inflammatory markers, CRP, IL-6 and ICAM-1 in atherosclerotic development and progression. In addition, fibrinogen and D-dimer, but not other haemostatic factors, were associated with progressive and incident peripheral atherosclerosis. Since D-dimer and fibrinogen are acute phase reactants, these data support the hypothesis that inflammation is more related to atherosclerosis than is hypercoagulation. Most importantly, the majority of the reported associations were not explained by increased levels of cardiovascular risk factors or pre-existing clinical or subclinical arterial disease. Thus these markers are more likely to have a causal than a consequential role in atherosclerotic disease.
26
Cosgrove, Megan. "The role of JAK2V617F-positive endothelial cells in aberrant haemostasis and thrombosis." Thesis, University of York, 2016. http://etheses.whiterose.ac.uk/15863/.
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Patients with MPNs commonly experience complications caused by dysfunctional haemostasis and thrombosis. Patient treatment is limited and aimed at preventing these adverse events, typically by low-dose aspirin therapy. However, a subset of patients experience increased risk of bleeding diatheses and these patients are at an even greater risk for experiencing complications if they are treated with low-dose aspirin. Currently, there are no methods for stratifying MPN patients to distinguish those who are at risk for thrombosis or bleeding. In order to improve MPN patient treatment, a better understanding of the mechanisms behind haemostasis and thrombosis complications is required. Here, we investigate the mechanisms of JAK2V617F activation in endothelial cells and the effects of JAK2V617F on endothelial function.
27
Subramaniam, Saravanan [Verfasser]. "Factor VII activating protease (FSAP) in thrombosis and haemostasis in vivo / Saravanan Subramaniam." Gießen : Universitätsbibliothek, 2014. http://d-nb.info/1068825588/34.
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Taylor, Andrew Alexander. "Haemostasis at open and laparoscopic myomectomy with the use of modified triple tourniquets." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1446543/.
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Objectives: To investigate the prevalence of haemostatic techniques at myomectomy. To investigate the effectiveness of modified triple tourniquets at open myomectomy and for the first time to pilot their use at laparoscopic myomectomy. Design: A questionnaire based postal survey. A randomised controlled trial (RCT) and a feasibility study Population All UK Consultant Obstetricians Gynaecologists. 38 patients with symptomatic fibroids undergoing open or laparoscopic myomectomy. Methods: A standard questionnaire postal survey. At open myomectomy a number 1 polyglactin suture was tied around the cervix to occlude the uterine arteries, and polythene (polyglactin at laparoscopic myomectomy) tourniquets were tied around the ovarian vessels. At the end of the procedure the ovarian ties were released but the uterine artery suture remained in situ. Outcome measures Use of haemostatic techniques at open, laparoscopic and hysteroscopic myomectomy. Intra-operative blood loss, post-operative blood loss, blood transfusion rates, operative morbidity, uterine blood flow, ovarian function, quality of life and effect on menstruation. Results: 59% responded to the survey. At open myomectomy 90% regularly used a haemostatic technique, with 85% prescribing pre-operative gonadotrophin releasing hormone agonists. Open myomectomy RCT there was less blood lost in the tourniquet group than in the control (p 0.0001). The volume in the pelvic drain postoperatively failed to reach statistical significance between the two groups. There were no differences in uterine artery Doppler resistance indices and ovarian function was unaffected by the tourniquets. Open myomectomy significantly improved menorrhagia and quality of life. In the laparoscopic study triple tourniquets were applied successfully and appeared effective. Conclusions: Modified triple tourniquets are effective in reducing bleeding at open myomectomy and appear safe with no obvious effect on uterine perfusion or ovarian function. Our feasibility study would suggest they can also be successfully used at laparoscopic myomectomy.
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Gong, Feng. "Design, development and testing of miniature instruments for flexible endoscopy." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322407.
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Luddington, Roger. "The development of a screening test for haemostasis using physiological levels of tissue factor." Thesis, De Montfort University, 2005. http://hdl.handle.net/2086/4303.
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Haj, Montaser A. "The influence of neutrophils and mononuclear leucocytes on the fibrinolytic response to severe sepsis." Thesis, University of Aberdeen, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295797.
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This study identified striking increase in plasma of plasminogen activator inhibitor 1(PAI-I), a major inhibitor of fibrinolysis levels in septic patients who are non-neutropenic. Neutropenic patients show less striking changes. Where shock occurs both groups of patients show very high levels of PAI-1. These observations suggest a role for leucocytes in PAI production. In the second section neutrophils are identified as containing PAI-1 in normal subjects, the levels rising significantly in sepsis. Monocytes contain no PAI-1 but do contain Plasminogen activator inhibitor 2(PAI-2) levels of which inhibitor also rise in sepsis. Normal neutrophils contained no PAI-2 but neutrophils from septic patients contained significant quantities of this inhibitor. In the third section mononuclear cells from septic patients are identified as enhancing PAI-1 production in cultured endothelial cell (EC). Septic neutrophils have a more complex effect on EC. Mononuclear cells and neutrophils therefore, both contribute to the fibrinolytic inhibition of septic disorders but by different mechanisms. Each cell type contains one of the major inhibitor of plasminogen activator and levels of these rise in sepsis. Both cell types from septic patients promote greater release of PAI-1 from endothelial cells than do cells from normal individuals. Inhibition of fibrinolysis by leucocytes may contribute to fibrin persistence in sepsis. This may be useful in localizing infection. If generalized, it may contribute to vascular occlusive complications of sepsis such as shock lung, acute renal failure or digital gangrene. Absence of leucocytes may account for the apparent reduction of vascular occlusive complications in leucopenic septic patients.
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Musa, Faiza. "Development of a human 3D tissue-engineered blood vessel model for the study of haemostasis." Thesis, Keele University, 2018. http://eprints.keele.ac.uk/5003/.
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In this project, we have designed, constructed, and validated a human tissue-engineered blood vessel construct (TEBV) to assess whether it could be used as a new model system in which to study thrombus formation under physiologically relevant conditions. A layer-by-layer fabrication technique was adopted to fabricate the TEBV. This allowed for the biological properties of both the medial and intimal layers of the construct to be assessed individually, as well as in combination as the full TEBV. The TEBV model was shown to mimic the anatomical structure and cellular phenotype of the native human artery. In addition, a novel technique for quantitatively assessing the pro- and anti-aggregatory properties of these constructs was developed, utilising real-time measurements of cytosolic Ca2+ signalling to assess real-time human platelet activation when exposed to the tissue-engineered blood vessels constructs. The real-time measurement of cytosolic Ca2+ signalling of human platelets when exposed to the TEBV models was shown to be a sensitive technique to assess the haemostatic properties of the 3-dimensional (3D) TEBV to validate the physiological relevance of the construct. Experiments conducted with this novel methodology, alongside other traditional platelet function assays, demonstrated that our TEBV had an anti-aggregatory intimal layer and a pro-aggregatory medial layer, consistent with the haemostatic functions of this blood vessel layers in vivo. We have also established an ex vivo ferric chloride (FeCl3) arterial injury model to be used as an alternative to intravital microscopy study of in vivo thrombus formation in mice models. Treatment of the TEBV with FeCl3 elicited a significant increase in platelet aggregation upon the surface of the construct when these cells were perfused over the construct at arterial shear stresses. By using this perfusion system, experiments also provided initial evidence that the use of the general anaesthetic ketamine, in intravital microscopy experiments may interfere with thrombus formation, and therefore could affect the validity of results seen in previous in vivo studies. In conclusion, we have successfully created a TEBV that is able to replicate the functional properties of the native vessel and which may be useful as a novel model to study human thrombus formation.
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Preston, Shaun. "A novel microwave transmission line with impedance matching structures for haemostasis of upper gastrointestinal bleeding." Thesis, Bangor University, 2018. https://research.bangor.ac.uk/portal/en/theses/a-novel-microwave-transmission-line-with-impedance-matching-structures-for-haemostasis-of-upper-gastrointestinal-bleeding(2d21c630-9b06-47bc-b689-9f9c011b5358).html.
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This research shows the development of a complete novel medical device capable of achieving haemostasis of upper gastrointestinal bleeding. A novel transmission structure has been designed and tested which includes a hollow central channel running through the inner conductor allowing for the delivery of fluid or introduction of clinical tools such as forceps, biopsy graspers or needles alongside the delivery of microwave energy. To facilitate the initial testing and subsequent clinical usage of the cable; multiple transformer structures were considered and developed both for the delivery of microwave and radio frequency energy. These allowed for the testing and characterisation of multiple cable prototypes developed throughout this research. In order to achieve the required clinical effect, namely coagulation of bleeding vessels, a solution which allowed optimal delivery of energy from the cable structure into the tissue at the treatment site was developed. Radiative tip prototypes were simulated, manufactured and tested to show matching between the lower impedance cable and the higher impedance tissue. Finally a number of complete devices were assembled and tested using microwave test equipment, on bench tissue testing using porcine liver and also during a pre-clinical investigation held at Northwick Park Institute for Medical Research, one of the UK’s leading charity-based independent Medical Research Institutes. Clinician feedback and histological analysis is presented within and show successful coagulation of multiple simulated oesophageal bleeds.
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Bonar, Roslyn. "Evaluation of quality issues in haemostasis testing for the identification of bleeding and thrombotic disorders." Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/16756.
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Haemostasis is a complicated and regulated process, which when disrupted (e.g., by a factor deficiency, excess presence of anticoagulants, presence of thrombophilia) can lead to bleeding or thrombosis. Laboratories help to assess haemostasis for investigated patients by performing a range of tests, and test quality is dependent on various processes including internal quality control (IQC) external quality assessment (EQA). Once a thrombosis has occurred, medical intervention is usually required in the form of anticoagulant therapy. Heparin, either unfractionated (UFH) or low molecular weight heparin (LMWH) is usually administered to patients to prevent or treat thrombosis. In Chapter 3 (Heparin anticoagulant therapy) the monitoring of UFH by the activated partial thromboplastin time (APTT) is explored, with variation in reported results attributed to different APTT reagent sensitivities and the many reagent/instrument combinations available. Compared to UFH, LMWH has a more predictable response and, in general, does not require monitoring. However, under certain circumstances, such as, impaired renal function, monitoring using the anti-Xa assay may be required to improve efficacy. Therefore, the APTT and anti-Xa assay, as performed by any given laboratory, must be done at the highest level of accuracy and reliability as possible, in order that clinicians can properly manage their patients based on these test results. Several international EQA programs have highlighted assay variations observed with these tests and data published in Chapter 3 provides comparative data from our geographical region. For many years, the progression from heparin therapy has been towards vitamin K antagonist (VKA) therapy (e.g., warfarin). These cause a prolongation of the Prothrombin time (PT) by diminishing the functional activity of Factors II (FII), VII (FVII), IX (FIX) and X (FX). VKA therapy has many limitations including, a narrow therapeutic range, interaction with many drugs and dietary influence. These issues mandate regular monitoring of patient anticoagulant status, which is usually achieved using the International Normalised Ratio (INR). This is a simple calculation (INR=(PT/MNPT)ISI) requiring the PT, mean normal prothrombin time (MNPT) and international sensitivity index (ISI). Despite international standardisation, there remains considerable concern regarding ongoing high levels of inter-laboratory variation, as generated by different laboratories using the same homogeneous plasma sample. This issue is highlighted in Chapter 4 (Vitamin K Antagonist anticoagulant therapy) and significant discrepancies continue to be evidenced in EQA environments, prompting additional investigations to determine causes and to identify potential inconsistencies of practice. Alternatives to traditional VKA therapy are now available for the treatment and prevention of arterial thrombosis (AF) and venous thromboembolism disease (VTE). The direct oral anticoagulants (DOACs) dabigatran, rivaroxaban and apixaban have been developed as not requiring laboratory monitoring; however, under certain clinical situations, laboratory testing may be indicated. Two separate studies were performed to assess the interference of these DOACs on a wide range of haemostasis tests. Specific assays are used to predict the level of DOAC, while in other assays these drugs caused interference and sub-optimal assay performance, leading to false positive or negative results. This is explored in Chapter 5 (Anticoagulant therapy using DOACs). One of the more complicated examples of clinical diagnosis of a thrombophilia disorder is represented by the Lupus Anticoagulants (LA), an important component of the autoimmune disorder antiphospholipid syndrome (APS). Challenges occur due to the heterogeneity of laboratory tests available and the differing approaches undertaken. Chapter 6 (Lupus Anticoagulant) evaluates EQA data for a complex but highly positive LA sample. Only 58% of survey participants correctly identified this sample as being positive for LA. Of the 34.7% participants who identified the sample as (falsely) LA negative, most incorrectly identified a (false) factor inhibitor. The debate over whether to utilise mixing studies in LA testing, with patient plasma mixed with normal pooled plasma before testing, is also discussed in Chapter 6. Progressing from thrombosis to bleeding disorders, Chapter 7 (Common Bleeding disorders) highlights the difficulty in diagnosis of von Willebrand Disease (VWD) and also the problems in the performance of FVIII inhibitor assays, as used to monitor patients with congenital and acquired Haemophilia. VWD is the most common inherited bleeding disorder, but its diagnosis can be difficult. Due to the heterogeneous nature of VWD, a panel of tests is required and these must be performed with highest degree of accuracy and reliability. Tests include both antigenic (VWF:Ag) and functional (VWF:RCo, VWF:Act and VWF:CB) assays, required for identification of the six subtypes of VWD. VWD testing is explored extensively in Chapter 7 (Common Bleeding disorders). The initial detection of factor inhibitors by laboratories is essential in clinical management of affected patients. The FVIII inhibitor is the most common and is directed against factor VIII coagulant (FVIII:C), resulting in an increased risk of bleeding. High interlaboratory variation (CVs ranging from 20-50%) in the factor inhibitor assay (including FVIII) have been previously reported by many EQA programs and this is extensively explored in Chapter 7 (Common Bleeding disorders). One of the contributing factors to the large interlaboratory variation is the vast array of methodologies used by laboratories. It has been previously identified that no two laboratories in our geographic area use identical methods for their inhibitor assay, thus increasing the potential for cross laboratory variation. Standardisation of the FVIII inhibitor assay over the past decade appears to be slow with no apparent improvement seen to reduce the interlaboratory variation. Overall, this thesis touches on many areas of haemostasis testing for the identification of bleeding and thrombotic disease, but specifically highlights the many quality issues in the performance and interpretation of these tests. Errors in patient test results can occur at multiple stages in the test process. Quality issues in haemostasis testing encompass pre-analytical, analytical and post analytical issues, and this thesis reports issues related to all these areas. However, given that laboratories are generally sent identical lyophilised samples for testing, together with the high degree of automation available, reduces the potential for analytical issues to occur, thereby facilitating primary focus on certain pre- and post-analytical issues. For example, many post analytical issues, particularly with VWD and LA testing, can be identified, where interpretations based on overall test results, can be offered by the laboratory to provide clinical guidance and enable clinicians to make the best possible decisions for patient clinical management of both bleeding and thrombotic disorders.
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Lindoff, Claes. "Haemostasis during pregnancy and perimenopausal age studies of fibrinolytic components and coagulation factors involved in vascular disease /." Lund : Dept. of Obstetrics and Gynaecology, Lund University, 1994. http://catalog.hathitrust.org/api/volumes/oclc/39750405.html.
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Leander, Karin. "Family history in relation to myocardial infarction, and analyses of gene-environment interactions involving factors of haemostasis /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-396-5/.
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McNally, Tracy Jane. "An investigation of the role of antiphospholipid antibodies and #beta#2 glycoprotein-I in the modulation of haemostasis." Thesis, University College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.339151.
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Kamiguti, Aura S. "Effects of jararhagin, a haemorrhagic metalloproteinase from Bothrops jararaca venom, on platelet and plasma proteins involved in haemostasis." Thesis, University of Liverpool, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261911.
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Stainer, Alexander. "The relationship between the metabolites of the dietary flavonoid quercetin, and haemostasis and thrombosis : an integrated systems approach." Thesis, University of Reading, 2018. http://centaur.reading.ac.uk/76013/.
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Quercetin is one of the most widely consumed flavonoids worldwide, and exerts numerous effects protective against cardiovascular disease, including the inhibition of platelet function. However, quercetin is extensively metabolised, and current data is limited regarding these metabolites. In this study, the anti-platelet effects of quercetin, and two methylated metabolites, tamarixetin and isorhamnetin, were investigated, to examine how anti-platelet efficacy is altered upon metabolism. Quercetin, tamarixetin and isorhamnetin inhibited collagen-stimulated platelet aggregation, and aggregation stimulated by ADP, thrombin and the thromboxane A2 mimetic U46619, at physiologically achievable concentrations. Granule secretion, integrin aIIbb3 activation and outside-in signalling, adhesion and spreading and calcium mobilisation were inhibited in a concentrationdependent manner; metabolism of quercetin can enhance or reduce anti-platelet effect. Due to high plasma binding, anti-platelet effects in platelet rich plasma and whole blood were investigated; significant inhibitory effects were maintained, with inhibition of clot retraction and thrombus formation under arterial flow conditions. The potential pharmacological importance of quercetin intake was investigated, with in vitro anti-platelet effects of novel quercetin formulations and an in vivo anti-thrombotic effect of an isoquercetin formulation after oral administration being demonstrated for the first time, and the identification of an interaction between the methylated metabolites and aspirin. To identify and predict important flavonoid interactions and potential inhibitory mechanisms, mathematical models of platelet aggregation and thrombus formation were developed, as was a pharmacokinetic/pharmacodynamic model of the dynamic anti-thrombotic actions of quercetin, which predicted optimal dosing regimens and highlighted the potential for increased anti-thrombotic effects upon altering quercetin metabolism. In summary, this study provided evidence for the potential of quercetin and its methylated metabolites in the inhibition of platelet function and thrombus formation, and identified interactions with aspirin, highlighting the potential of quercetin as an anti-platelet dietary compound or supplement, and identified some of the mechanisms underlying these actions.
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Mina, Ashraf Anis Wahba. "Improving and Implementing Diagnostic Tools in Pathology with a Focus on Haemostasis and Association with Select Endocrine Disorders." Thesis, The University of Sydney, 2013. http://hdl.handle.net/2123/10599.
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The literature and evidence base associating haemostatic dysfunction associated with some of endocrine disorders as major risk factors and causes of human morbidity and mortality was reviewed and published. A detailed protocol to define and develop instrument selection and evaluation and implementation in pathology and research, also its impact on method development and objective evaluation was developed and published. A new quality control model using performance goals based on biological variation in External Quality Assurance Schemes was developed and published. A robust and cost effective method for estimating iodine as indicator of thyroid abnormality which can be used to identify patients with thyroid disorders that are prone to risk of bleeding and/or thrombosis was developed and published. A novel functional assay to estimate Von Willbrand factor (VWF)/antigen and collagen binding was developed and published. Evaluation of short activated partial thromboplastin times (APTT), as potential representation of a complex hypercoagulant milieu that could feasibly contribute to thrombotic risk, was assessed and published. Assessment of the relationship between short APTTs, thrombin generation, procoagulant factors [fibrinogen and Factors (V, VIII, IX, XI and XII)], VWF, and procoagulant phospholipid activity was also achieved and published. A study designed to investigate select haemostasis, endocrine and biochemical parameters in women who undergo in-vitro fertilisation, before and after stimulation with follicle stimulating hormone was achieved and submitted for publication.
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Morais, Karen Batista de. "Purificação e caracterização da antitrombina do plasma da serpente Bothrops jararaca (Wied, 1824) (Ophidia: Viperidae, Crotalinae)." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/41/41135/tde-13072009-160524/.
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O presente trabalho teve como objetivo caracterizar o desenvolvimento da semente de Araucaria angustifolia através da proteômica comparativa, buscando compreender as alterações fisiológicas e metabólicas que ocorrem durante esse processo. Inicialmente, foram avaliados três diferentes metodologias de extração de proteínas. A metodologia composta por solução de extração contendo 7 M de uréia, 2 M de tiouréia, 1% de ditiotreitol, 2% de Triton-100, 1 mM de fluoreto de fenilmetilsulfonil e 5 µM de pepstatina, seguido de precipitação em 20% de ácido tricloroacético apresentou géis de maior resolução e reprodutibilidade, tendo sido escolhida como metodologia de extração protéica para o estudo das alterações no proteoma da semente de A. angustifolia. Uma dificuldade associada ao estudo do proteoma de espécies não sequenciadas é a baixa representatividade nos bancos de dados protéicos, resultando em identificações baseadas em homologia. Estratégias proteômicas baseadas em fracionamento em gel resultam em grandes contaminações por fragmentos de queratina. Sendo assim, foi desenvolvido um programa de remoção de espectros de baixa qualidade para utilização em proteômica baseada em homologia. As análises mostraram que o programa reduz o tempo de busca, melhora a qualidade dos alinhamentos e não resulta em perda de identificações positivas. Finalmente, utilizando as metodologias descritas, foram estudadas as alterações no proteoma durante o desenvolvimento da semente de A. angustifolia. Noventa e seis proteínas foram identificadas e agrupadas de acordo com sua função biológica e padrão de detecção. Os resultados obtidos permitiram o estabelecimento de marcadores protéicos no início e final do desenvolvimento embrionário. A análise das proteínas abundantes no início da embriogênese indica um maior controle no metabolismo oxidativo em relação aos estádios finais. Contrariamente, o final da embriogênese é caracterizado por um alto metabolismo de assimilação de carbono e acúmulo de proteínas de reserva. As implicações dos resultados obtidos no controle e melhoramento de sistemas de embriogênese somática na espécie também foram discutidasThe aim of the present work was to characterize the seed development of Araucaria angustifolia through proteomics in order to understand the physiological and biochemical changes during this process. For that, initially, three different protein extraction methods were evaluated. The extraction based on protein solubilization in 7 M urea, 2 M thiourea, 1% dithiothreitol, 2% Triton-100, 1 mM phenylmethylsulphonyl fluoride, 5 µM pepstatin, followed by 20% trichloroacetic acid precipitation showed the highest gel resolution and reprodutivity and, thus, was chosen to be used in the analysis of the proteome of A. angustifolia seeds. One aspect that hampers the proteome study of unsequenced species is the low protein representativity in databases. So, protein identification is usually carried out through homology. Strategies based on 2-DE result in high keratin contamination. In the present work a spectra filtering software was developed and evaluated for use in homology driven proteomics. The software reduced the time of search, improved alignment quality and did not result in lost of positive identifications. Finally, using the described strategies, the changes in the proteome of A. angustifolia seeds were studied. Ninety six proteins were identified and classified according to their biological functions and expression profiles during seed development. The identified proteins may be used as protein markers of early and late embryogenesis. Proteins involved in the control of oxidative metabolism were highly expressed during the early stages of seed development; while, carbon metabolism and storage proteins were highly expressed in late stages. Considerations on the improvement and control of somatic embryogenesis through medium manipulation and protein markers screening using data generated are also discussed.
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Lines, Simon. "The influence of vitamin E bonded haemodialysis membranes on erythropoiesis stimulating agent requirements, oxidative stress, inflammation, haemostasis and outcomes." Thesis, University of Leeds, 2013. http://etheses.whiterose.ac.uk/5871/.
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Introduction: Haemodialysis (HD) patients have high rates of cardiovascular (CV) disease and mortality yet the reasons for this have not been fully elucidated. High doses of erythropoiesis stimulating agents (ESAs), increases in oxidative stress and inflammation, and alterations to the fibrin clot phenotype are all possible contributors. Vitamin E (VE)- bonded dialysis membranes are purported to have favourable effects on a number of these parameters which were tested here in the setting of a randomised controlled trial. Methods: Patients were randomised to HD with VE-bonded polysulfone membranes or non-VE-bonded equivalents and followed for 12 months. Data on anaemia parameters were collected monthly and blood tests were performed at baseline, 6 and 12 months for the measurement of oxidative stress (oxidatively modified-low density lipoprotein, thiobarbituric acid reactive species), inflammation (C-reactive protein, complement components C3, SC5b-9, factor D, properdin) and fibrin clot properties. Contemporaneous data were collected on CV events and death. Results: Of the 260 patients enrolled, 123 were randomised to dialysis with VE-bonded membranes. Analysis of the full dataset revealed no differential effects of the VEmembranes on ESA requirements, oxidative stress, inflammation, fibrin clot structure or clinical outcomes. Key findings included a potential ESA-sparing effect of the VEmembranes in ESA resistant patients, a progressive decline in C3 levels over 12 months and associations between the levels of C3 and SC5b-9 at baseline and the subsequent risks of dying or experiencing a CV event. Conclusions: There were no benefits in switching prevalent HD patients to dialysis with VE-bonded dialysis membranes with the exception of possible utility in ESA-resistant patients. The novel finding suggesting a link between the complement system and poor outcomes in HD patients may provide further insights to explain the high rates of CV disease and mortality for this patient group and merits further study.
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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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Linden, Matthew D. "The haemostatic defect of cardiopulmonary bypass." University of Western Australia. School of Surgery and Pathology, 2003. http://theses.library.uwa.edu.au/adt-WU2006.0009.
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[Truncated abstract] Cardiac surgery involving cardiopulmonary bypass is a complex procedure that results in significant changes to blood coagulation, fibrinolytic biochemistry, platelet number and function, and the vasculature. These are due to pharmacological agents which are administered, haemodilution and contact of the blood with artificial surfaces. Consequently there are significant risks of thrombosis and haemorrhage associated with this procedure. The research presented in this thesis utilises in vitro, in vivo, and a novel ex vivo model to investigate the nature of the haemostatic defect induced by cardiopulmonary bypass. The components studied include the drugs heparin, protamine sulphate, and aprotinin, different types of bypass circuitry (including heparin bonded circuits) and procedures such as acute normovolaemic haemodilution. Patient variables, such as Factor V Leiden, are also studied. Each of these components is assessed for the effects on a number of laboratory measures of haemostasis including activated partial thromboplastin time, prothrombin time, activated protein C ratio, antithrombin concentration, heparin concentration, thrombin-antithrombin complex formation, prothrombin fragment 1+2 formation, markers of platelet surface activation and secretion, activated clotting time, haemoglobin concentration and coagulation factor assays.
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Jones, Peter. "Effects of separate propranolol, aspirin and glyceryl trinitrate administration, prior to submaximal exercise, on blood haemostasis, blood rheology and blood lipid profiles." Thesis, Liverpool John Moores University, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.436557.
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Pike, Gillian. "Investigation of the role of global haemostasis assays and bleeding scores in the assessment and management of patients with Factor XI deficiency." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/investigation-of-the-role-of-global-haemostasis-assays-and-bleeding-scores-in-the-assessment-and-management-of-patients-with-factor-xi-deficiency(0ff0defc-ba60-4f91-b283-86cb3fe0c9c5).html.
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The clinical management of Factor XI (FXI) deficiency is problematic due to the marked phenotypic heterogeneity between individuals with this disorder and the lack of a reliable test to predict bleeding risk. FXI-deficient individuals are currently at risk of being over- or under treated, with associated risks of transfusion-related complications or haemorrhage respectively. The improvement of care of FXI-deficient patients requires the development of measures that can predict bleeding phenotype and enable the identification of individuals who need treatment at times of haemostatic challenge. In addition, for those requiring treatment, there is a need for development of tests which can determine the optimal type and dose of FXI replacement on an individually tailored basis, as well as assays which can accurately monitor the effect of treatment and guide clinicians in the requirement for further perioperative treatment. This thesis addresses these objectives by studying global haemostasis assays and bleeding scores as tools to predict bleeding tendency and by studying the utility of global haemostasis assays as potential tests by which FXI replacement treatment can be determined and monitored. For prediction of bleeding tendency, this research demonstrated that the thrombin generation assay (TGA) was able to differentiate bleeding tendency provided the sample conditions used in the assay were optimised to assess FXI involved coagulation pathways thought to be of relevance in vivo: using platelet rich plasma with inhibition of in vitro contact activation and a low tissue factor trigger. Thromboelastometry measured using the same sample type was similarly able to distinguish bleeding phenotype. However, when the potential clinical utility of the assays was compared using receiver operating characteristic curve analysis, thromboelastometry was inferior to TGA as an identifier of bleeding tendency. When the thromboelastometry sample type used was whole blood, or where assays were performed in the presence of tissue plasminogen activator the assays did not differentiate bleeding phenotype. For purposes of treatment planning, the potential of the TGA to determine the optimal dose of FXI replacement was assessed by in vitro spiking experiments using two commercially available FXI concentrates and samples from individuals with major FXI deficiency. Each concentrate improved thrombin generation, but dose response curves were found to differ, suggesting different properties for the two products. The clinical utility of the approach was then demonstrated with comparable TGA results obtained in ex vivo samples from patients treated with FXI concentrate and baseline samples spiked in vitro with equivalent amounts of the same FXI concentrate. The utility of global haemostasis assays to monitor the effect of FXI replacement in FXI-deficient individuals undergoing surgery was also tested. Improvement in assay parameters after treatment with solvent-detergent fresh frozen plasma or FXI concentrate was demonstrated suggesting assay value in FXI replacement monitoring. Finally the use of recently developed bleeding assessment tools and bleeding scores as descriptive, diagnostic or predictive measures was tested along with correlation with FXI:C levels and TGA parameters. This analysis confirmed that bleeding scores have a limited value in the clinical assessment of FXI deficiency.
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Hasson, Sigdi S. Anwer Abdo. "DNA immunisation to generate snake antivenom : cloning and characterisation of novel cDNAs encoding haemostasis-disruptive venom toxins of saw scaled viper, Echis ocellatus." Thesis, University of Liverpool, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.403219.
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Nienaber, Cornelie. "Haemostatic variables in African adolescents : the PLAY study / Cornelie Nienaber." Thesis, North-West University, 2006. http://hdl.handle.net/10394/1322.
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Macedo, Carolina Sales Vieira. "Efeito do implante de etonogestrel sobre a agregação plaquetária de mulheres hígidas." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/17/17145/tde-12012007-123734/.
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Introdução: Estudos iniciais sugeriram que o risco para tromboembolismo venoso (TV) era atribuído ao componente estrogênico dos contraceptivos de forma dose-dependente. Estudos epidemiológicos têm sugerido que o risco para TV é maior com contraceptivos combinados que contêm progestagênios de terceira geração (gestodeno, desogestrel) comparados com aqueles com progestagênios de segunda geração (levonorgestrel). Esses achados inesperados têm sido alvo de muitos debates sem uma explicação definitiva. Assim, a questão das diferenças nas propriedades de cada progestagênio sobre a hemostasia tem sido levantada. Apesar dos progestagênios não serem associados a alterações marcantes nos parâmetros hemostáticos, existem poucos estudos sobre os efeitos dessas drogas, especialmente os progestagênios de terceira geração, no sistema hemostático. Objetivo: Avaliar o efeito do implante subdérmico de etonogestrel sobre a agregação plaquetária de mulheres hígidas, em seis meses de tratamento. Casuística e Métodos: Vinte e quatro mulheres saudáveis e voluntárias foram selecionadas neste estudo longitudinal e prospectivo, para usar um implante contraceptivo subdérmico de etonogestrel (metabólito biologicamente ativo do desogestrel). A agregação plaquetária foi avaliada em todas as mulheres, exceto uma, no período pré-inserção e após um, três e seis meses da inserção do implante. A agregação plaquetária foi induzida com adrenalina 50 µM, colágeno 10 µg/ml, colágeno 5 µg/ml, ADP 35 µM e ADP 17,5 µM. A análise estatística foi feita com o teste de Wilcoxon para comparar a diferença entre cada período de tratamento com os valores pré-tratamento. Resultados: Houve uma redução transitória, estatisticamente significativa, na mediana do percentual máximo de agregação plaquetária de 27%, 14% e 11%, respectivamente, com colágeno 5 µg/ml, adrenalina 50 µM e colágeno 10 µg/ml, observada um mês após a inserção do implante comparado ao valor pré-inserção (p< 0,05). A agregação plaquetária com esses agonistas retornou ao seu valor basal, após seis meses da inserção. Com outros agonistas, como o ADP 35 µM e ADP 17,5 µM, não se observou o mesmo fenômeno. Conclusão: Os resultados deste estudo mostram, pela primeira vez, que o uso do implante de etonogestrel está associado à redução transitória, mas significativa, da agregação plaquetária, observada em um mês de uso do contraceptivo, a qual retorna a seus valores normais em seis meses da inserção do implante.Introduction: Several studies have suggested that the risk of venous thromboembolism (VTE) is attributable to the estrogen component of a contraceptive in a dose-dependent manner. Recent epidemiological studies have suggested that the risk of VTE was higher with contraceptives containing third-generation progestagens (desogestrel, gestodene) when compared with second-generation progestagens (levonorgestrel). These unexpected findings have been the subject of many debates with no definitive explanation and the question of differences in hemostatic properties of each progestagen has been raised. Although progestagens are not associated with marked changes in hemostatic variables, there are few studies on the effects of these drugs, especially third-generation progestagens, on the hemostatic system. Objective: To evaluate the acute effect of a long-term contraceptive implant of etonogestrel on platelet aggregation in healthy women. Material and Methods: Twenty-four healthy volunteer women were enrolled in this prospective longitudinal study, to use a subdermal contraceptive implant of etonogestrel (the biologically active metabolite of desogestrel). Platelet aggregation was measured in all users, except one, at baseline and after 1, 3 and 6 months of treatment. Platelet aggregation was induced with 50 µM adrenalin, 10 µg/ml collagen, 5µg/ml collagen, 35 µM ADP and 17,5 µM ADP. Statistical analysis included the Wilcoxon test to compare differences between each period of treatment from baseline. Results: Statistically significant 27%, 14% and 11% reductions of platelet aggregation with 5 µg/ml collagen, 50 µM adrenalin e 10 µg/ml collagen, respectively, were observed at 1 month of treatment (p < 0,05). Platelet aggregation returned to baseline values at 6 months of treatment with these reagents. Platelet aggregation did not show any statistic difference with ADP. Conclusions: The result of this study shows for the first time that an etonogestrel implant is associated with a transitory, but significant, reduction in platelet aggregation after the first month of treatment, which returns to normal values by 6 months of therapy.
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Ford, Zoe. "A comparison of a 4% modified fluid gelatin and a 6% hydroxyethyl starch on haemodilution colloid osmotic pressure haemostasis and renal parameters in healthy ponies." Diss., University of Pretoria, 2015. http://hdl.handle.net/2263/57307.
Full textAbstract:
Reasons for performing study: Adverse effects on renal health and haemostasis have been documented in human patients administered hydroxyethyl starches (HESs). Gelatins could provide useful substitutes should similar adverse effects be identified in horses.
Objectives: To compare the effects of a 4% modified fluid gelatin (MFG) with a 6% (130/0.4) HES on haemodilution, colloid osmotic pressure (COP), haemostasis and renal parameters in healthy ponies.
Study Design: Randomised crossover experiment. Methods: Three treatments (A=10 ml/kg bwt HES, B=10 ml/kg bwt MFG and C=20 ml/kg bwt MFG) were administered to 6 healthy ponies with a 1-week washout period. Haematocrit, platelet count, total serum protein, COP, thromboelastography (TEG), prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen were measured at baseline and at multiple time points up to 24 h post-infusion. Serum creatinine, urine specific gravity (USG), urine protein: creatinine ratio (UPC), urine gamma glutamyltransferase:creatinine ratio (UGC) and urine sediment examination (USE) were performed before and 24 h after each treatment, as well as one week after the final treatment.
Results: All treatments resulted in significant haemodilution and increases in COP, with treatment C having a significantly greater effect on haematocrit than other treatments. The platelet count decreased with all treatments and was significantly lower following treatment C compared with treatment B. No clinically relevant differences were observed in any of the TEG parameters within or between treatments. No significant differences in PT, aPTT or fibrinogen were observed between treatments. Serum creatinine, UPC and UGC did not change significantly between pre- and post-study measurements. USG and USE remained within normal limits.
Conclusions: MFG could be considered as an alternative to HES for volume expansion and oncotic support. Neither MFG nor HES were associated with clinically significant adverse effects on haemostasis or renal parameters.Dissertation (MSc)--University of Pretoria, 2015.
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Companion Animal Clinical Studies
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