Dissertations / Theses: 'Proteins in blood coagulation'

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Smith, Brian. "Protein models in blood coagulation and fibrinolysis." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239327.

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Carlsson, Karin. "Tissue Factor in Complex : Studies of interactions between blood coagulation proteins." Doctoral thesis, Linköpings universitet, Biokemi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-63688.

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Many biological processes rely on specific protein-protein interactions, for example immune responses, cell signaling, transcription, and blood coagulation. Blood coagulation is initiated when a vessel wall is damaged, exposing tissue factor (TF) to the circulating factor VII/factor VIIa (FVII/FVIIa) which results in the formation of the TF:FVIIa complex and thereby the initiation of blood coagulation. One of the substrates for the TF:FVIIa complex is factor X (FX), which is activated to factor Xa (FXa), subsequently leading to a series of reactions resulting in clot formation. Tissue factor pathway inhibitor (TFPI) is the major physiological inhibitor of the sTF:FVIIa complex, involved in regulation of coagulation by forming the TF:FVIIa:FXa:TFPI complex. Occasionally, the blood coagulation mechanism malfunctions, resulting in conditions such as the inability to stop bleeding or thrombosis. The fact that TF is the main initiator of the coagulation makes this an interesting protein to study, in the hunt for means to interfere with players involved in the blood clotting process. Throughout the studies included in this thesis the site-directed labeling technique is utilized to attach spectroscopic probes to cysteines, introduced at specific positions by mutagenesis, in the protein of interest. These fluorescent or spin-probes are sensitive for changes in their immediate environment and can thus, for example be used to monitor protein-protein complex formation and conformational changes. No complete structure has been obtained as yet for the large complex involving sTF, FVIIa, FXa, and TFPI. Therefore, we introduced a fluorescent probe at specific positions in soluble tissue factor (sTF) and the changes in fluorescence emission were detected upon sTF:FVIIa:FXa:TFPI complex formation. From these measurements it was concluded that not only parts of the C-terminal domain of sTF (TF2), but also residues in the N-terminal domain (TF1) are involved in binding to FXa in the quaternary complex. In order to investigate conformational changes occurring in the extended interface between sTF and FVIIa upon binding of different inhibitors spectroscopic probes were introduced in sTF, in the vicinity of the interaction region. From the obtained data it was concluded that the exosite-binding inhibitor E-76 induces equivalent structural changes at the interface of sTF and the protease domain (PD) of FVIIa, as do the active-site inhibitors FFR and TFPI, i.e. makes the region around the active-site more compact. Binding of these inhibitors shows similar effects despite their differences in size, binding site, and inhibitory mechanism. In addition, the Ca2+ dependence of the formation of the sTF:FVIIa complex was studied. Association between sTF and FVIIa during Ca2+ titration begins by Ca2+ binding to the first EGF-like domain of FVIIa. However, Ca2+ saturation of the γ-carboxyglutamic acid-rich (Gla) domain of FVIIa is required for complete sTF:FVIIa complex formation, and we were also able to detect that a Gla domain with vacant Ca2+ sites hinders the docking to sTF. Finally, we investigated the structural changes of free inhibited FVIIa upon sTF and Ca2+ binding by FRET and quenching measurements. From this it was concluded that inhibited FVIIa does not seem to undergo large global structural changes upon binding to sTF, when taking the dynamics of free FVIIa into account. However, Ca2+ binding induces minor local conformational changes in the active-site region of the PD of inhibited FVIIa and subsequent binding of sTF causesfurther structural rearrangements in this area.

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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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Holland, Susan Katrina. "X-ray studies of proteins of medical and biological interest." Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.236327.

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Kassaar, Omar. "Structural and functional studies of histidine-rich glycoprotein in relation to its roles in angiogenesis and coagulation." Thesis, University of St Andrews, 2014. http://hdl.handle.net/10023/5548.

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Histidine-rich glycoprotein (HRG) is a plasma protein that regulates key cardiovascular processes such as coagulation, angiogenesis and immune response. The protein consists of six distinct functional domains: two N-terminal domains (N1 and N2), two proline-rich regions (PRR1 and PRR2), a central histidine-rich region (HRR) and a C-terminal domain. The HRR binds Zn²⁺, which alters the affinity of HRG towards various ligands including the anticoagulant, heparin. A key aim of this study was to structurally characterise HRG. The 1.93 Å crystal structure of the HRG N2 domain presented here represents the first crystallographic snapshot of the molecule. The N2 domain is cystatin-like and N-glycosylated at Asn184. An S-glutathionyl adduct was observed at Cys185, providing in vivo evidence that release of an anti-angiogenic HRR/PRR fragment is controlled in part by a redox mechanism, representing a novel further role for GSH in regulation of angiogenesis. Since Zn²⁺ regulates some of the functions of HRG, the dynamics of Zn²⁺ in plasma were investigated using a combination of ITC, ELISA and thrombin assay systems. Zn²⁺ is normally associated with albumin in circulation, but its ability to bind Zn²⁺ is allosterically inhibited upon fatty acids binding to albumin. Elevated plasma fatty acid levels are associated with some disease states. It is proposed that this may alter the proportion of Zn²⁺ bound to HRG, which could in turn activate thrombin to promote coagulation. These studies provide evidence to suggest that Zn²⁺-dependent activation of HRG (following fatty acid binding to albumin) may play a role in the development of haemostatic complications in susceptible individuals. Finally, the Zn²⁺ binding ability of albumin was probed in order to locate unidentified sites using recombinant albumin mutants. H9A, H67A, E252A, D256A and H288A mutants all exhibited diminished Zn²⁺ binding ability, indicating that these residues are involved directly or indirectly in Zn²⁺ binding.

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Grunkemeier, John M. "Effect of adhesion proteins and surface chemistry on the procoagulant state of adherent platelets /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/8087.

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Popescu, Narcis Ioan. "Regulation of procoagulant activity of cell surface tissue factor." Oklahoma City : [s.n.], 2010.

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Jenkins, Meredith E. "An examination of the human fibrinogen-like protein2 sequence variations and genetic expression by human endothelial cells /." unrestricted, 2005. http://etd.gsu.edu/theses/available/etd-07222005-093438/.

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Thesis (M.S.)--Georgia State University, 2005.
Title from title screen. Roberta Attanasio, committee chair; P.C. Tai, W.C. Hooper, committee members. Electronic text (57 p. : col. ill.) : digital, PDF file. Description based on contents viewed Aug. 15, 2007. Includes bibliographical references (p. 55-57).

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Evington, J. R. N. "Protein-polysaccaride interactions and the catalysis of the thrombin/antithrombin reaction." Thesis, University of Bristol, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370826.

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Bakker, Harm Marten. "Accelerin the activated form(s) of human blood coagulation factor V /." Maastricht : Maastricht : Rijksuniversiteit Limburg ; University Library, Maastricht University [Host], 1994. http://arno.unimaas.nl/show.cgi?fid=6954.

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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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Hughes, Qunitin William. "Hormonal regulation of the anticoagulant Protein S." University of Western Australia. School of Surgery and Pathology, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0247.

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[Truncated abstract] Every year thousands of individuals suffer from thrombotic related complications that in some cases can be fatal and every year millions of women take some form of hormonal contraceptive. In some cases, there is a cause and effect relationship between the two as users of the combined oral contraceptive pill have an increased risk of developing a thrombotic event. Increased circulating levels of oestrogen cause a prothrombotic shift in the coagulation cascade resulting from upregulation of several procoagulant proteins and a decrease of key anticoagulant proteins. One of the most oestrogen sensitive anticoagulants is Protein S (PS), a product of the PROS1 gene. PS acts as a cofactor to activated protein C (aPC) and the PS-aPC complex serves to downregulate clot formation by deactivating the tenase and prothrombinase complexes via proteolytic cleavage of activated factors VIII and V, respectively. As such, low PS levels are associated with an increased risk of developing thrombotic disorders such as pulmonary embolism, stroke or coronary thrombosis and deep vein thrombosis. During pregnancy when oestrogen levels increase, a steady decline in PS is evident in the early weeks of gestation and continues to decrease to below the normal range in the 2nd trimester, remaining there until post-partum. In addition, reduced free and total PS levels are observed in users of the combined oral contraceptive (COC) pill that contains an oestrogen and a progestin. Interestingly, users of 3rd generation COCs have significantly greater reductions of PS than do 2nd generation COC users. The difference between the two forms is the type of progestin, not the oestrogen, which is predominantly ethinyl oestradiol in the majority of commercially available preparations. At present, a mechanism to describe the relationship between oestrogen and/or progesterone associated with the observed in vivo changes in the levels of PS has not been identified. The aim of this thesis was to define the molecular mechanisms involved in the regulation of PS expression by oestrogen and progesterone. In this study, a Combined Single-stranded conformational analysis and Heteroduplex Analysis (CSHA) iv methodology was optimised for screening both PROS1 DNA and mRNA for the detection of mutations. '...' This may explain why users of 3rd generation COCs display a greater reduction in circulating PS levels compared to 2nd generation users. To investigate potential PS interactions with other proteins that could be hormonally regulated, a yeast-2-hybrid (Y-2-H) screen was performed using the PS molecule as a 'bait' against molecules derived from liver and bone marrow cDNA libraries. A clone that contained a portion of another haemostatic protein, Protein Z (PZ) was isolated and confirmed via sequencing. As no full length PZ clones were identified, a second Y-2-H screen was performed once again using the PS molecule as bait and the PZ molecule as the fish. Interaction between the two proteins was shown to be possible via the successful growth of colonies on triple knock out selective media and by positive ß-galactosidase activity.

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Wallstedt, Maria. "Evaluation of blood interactions with a drug loaded protein matrix." Thesis, Linköpings universitet, Tillämpad Fysik, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-68306.

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Many things might happen in the body when a titanium implant is inserted into bone. Examples are activation of the immune system and imbalance between bone formation and bone resorption, which might lead to damaged bone around the implant and at worse, loosening of the implant. Bisphosphonates, BP’s, is a class of drugs that is able to decrease the osteoclast (bone resorption cell) activity and thereby strengthen the bone. FibMat2.0 is a fibrinogen matrix and consists of a thin protein layer which can be applied on an implant and act as a local drug delivery system. The work in this thesis was divided into two parts where aim of the first part was to study FibMat2.0 with integrated BP’s, and their effect in the presence of blood. The aim for the second part was to determine whether it was possible to incorporate antithrombotic drugs into the fibrinogen matrix. No detection method for the amount of drugs incorporated into the fibrinogen matrix was used but the fact that the drugs gave effect was verifying that it is possible to integrate other drugs than BP’s into FibMat2.0. Methods that have been used in the experiments in presence of blood are imaging of coagulation, fluorescence microscopy and cone-and-plate. For the first part, the results showed that surfaces incubated with fibrinogen and fibrinogen with integrated BP’s act alike in regard to coagulation and platelet adhesion. Compared to titanium, which is known to be a biocompatible material, the surfaces with fibrinogen and fibrinogen with BP’s behave similar in regard to platelet adhesion. When it comes to coagulation, the surfaces coated with fibrinogen with or without an addition of BP’s have shown a longer coagulation time compared to the clean titanium surface. For the second part, some conclusions have been drawn according to the results. Heparin and hirudin have shown anticoagulant effects when integrated in the matrix. The platelet inhibitor cangrelor seemed to have better effect when added in blood and incubated compared to incubation with the platelet inhibitor on the surface before incubation in blood. Finally, when combining heparin and cangrelor, very clear differences in regard to formation of fibrin network could be seen. It seems promising to be able to load different kind of drugs in FibMat2.0.

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Karlsson, Cecilia. "Studies of unspecific interaction between the Aβ antibody 6E10 and blood coagulation protein factor X." Thesis, Linköpings universitet, Institutionen för fysik, kemi och biologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-82346.

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Alzheimer’s disease is neurodegenerative with amyloid plaque and neurofibrillary tangles as pathological hallmarks. The most abundant component in the amyloid plaque is the amyloid-β (Aβ) peptide, with presence of both isoform Aβ40 and Aβ42. In immunological methods studying the Aβ peptide a specific monoclonal antibody, 6E10, is routinly being used. In this master thesis work unspecific binding of 6E10 antibody to the blood coagulating protein factor X has been investigated. Factor X is a protein in the blood coagulation cascade where it forms protein complex that activates thrombin. Non-hemostatic functions with connections to nerves and Aβ peptide are also known. Studies with Western blot show clear binding of 6E10 to denatured factor X. Interaction studies with ELISA gives uncertain results, where binding is found but no clear binding curve is obtained. Studies with native factor X in real time measurements with SPR gave no binding at all. These results suggest binding to denatured factor X. Immunohistochemistry studies of colocalisation of factor X and Aβ peptide gave clear evidence that factor X and Aβ are found near each other in mouse brain tissue. Factor X is located outside the blood vessels and Aβ is located at the inside.

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Wu, Yuguang. "Protein and platelet interactions with polyurethanes /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/8027.

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Iwashita, Claudia. "Novas estratégias de purificação dos fatores de coagulação Fator VIII e Proteína C a partir de plasma humano empregando cromatografia líquida." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-01062012-111458/.

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Neste trabalho estudou-se a purificação de fator VIII de coagulação (FVIII) e da Proteína C (PC) por cromatografia. Em coluna ANX Sepharose FF como primeira etapa de purificação do plasma permite a eluição do FVIII e da PC com bom fator de purificação, mas não a separação destas. Propomos a separação de FVIII e PC empregando cromatografia de afinidade a metal (IMAC) empregando Cu2+, Ni2+, Zn2+, Co2+ e Fe3+ e dessorção empregando imidazol, cloreto de amônio e variação de pH. Em colunas de Fe3+ e Ni2+ as proteínas praticamente não se ligaram à resina. Em IMAC-Co2+, a PC não é adsorvida pela resina enquanto o FVIII pode ser eluído com imidazol 100 mM. Em IMAC-Cu2+ a PC eluiu com imidazol 10mM e o FVIII com 200mM. Não foi possível eluir as proteínas nem com NH4Cl 1M nem quando o pH foi abaixado até 4,0. Em IMAC-Zn2+ a PC não é adsorvida e o FVIII eluiu com imidazol 200mM ou NH4Cl 1M. Diminuindo-se o pH, a recuperação da atividade do FVIII foi baixa. Concluímos que IMAC-Co2+ apresentou os melhores rendimentos e melhores fatores de purificação para as 2 protéinas.
In this work purification methods for the coagulation factor VIII (FVIII) and Protein C (PC) by chromatography was studied. The use of ANX Sepharose FF column as the first purification step allows the elution of FVIII and PC with good purification factors, but not its separation. We propose the separation of FVIII and PC using immobilized metal ion affinity chromatography (IMAC) using Cu2+, Ni2+, Zn2+, Co2+ and Fe3+ and desorption employing imidazole, ammonium chloride and pH variation. In the columns containing Fe3+ and Ni2+ metal ions, proteins did not adsorb to the resin. In IMAC-Co2+, PC was not adsorbed to the resin, while FVIII could be eluted with 100 mM imidazole. In IMAC-Cu2+ PC could be eluted with 10 mM imidazole and FVIII with 200 mM. It was not possible to elute the proteins from IMAC-Cu2+ column with either 1M NH4Cl or when pH was descreased to 4,0. In IMAC-Zn2+, PC was not adsorbed and FVIII could be eluted with 200 mM imidazole or 1 M NH4Cl. We conclude that IMAC-Co2+ presented the best yield and purification factors for the 2 proteins.

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Jordan, Sumanas W. "A mathematical model of tissue factor-induced blood coagulation: discrete sites of initiation and regulation under conditions of flow." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/33907.

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A mathematical model of blood coagulation under defined flow conditions, initiated and modulated by spatially discrete regions of surface bound tissue factor (TF) and thrombomodulin (TM), respectively, is presented. The model incorporates fluid phase and surface-associated reactions of the extrinsic, intrinsic, and common pathways, as well as three inhibitory pathways. The spatially heterogeneous model is formulated by finite element method, and an effective prothrombotic zone, which quantifies the spatial propagation of thrombin generation is defined. Characteristic features of coagulation are simulated under physiologic conditions, and the behavior of the system in response to perturbations in TF and TM surface densities, TF site dimensions, and wall shear rate is explored. The major findings of these studies include: (i) The model system responds in an 'all-or-none', threshold-like manner to changes in model parameters. (ii) It was found that prothrombotic effects may extend significantly beyond the dimensions of the spatially discrete site of TF expression in both axial and radial directions. (iii) The relationship between the length of the effective prothrombotic zone and the interval distance between tandem sites of TF expression dictate the net response of the system. Additive prothrombotic effects of sub-clinical lesions as well as suppressive antithrombotic effects of intervening TM-containing regions were observed. Secondly, the computational model is applied to calculate an individualized, systems-based metric of clotting potential for 210 pre-menopausal women in the Leiden Thrombophilia Study (LETS). The simulated variable was found to be a highly predictive parameter for deep venous thrombosis risk.

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Szunyogová, Eva. "Understanding the pathogenesis of spinal muscular atrophy by determining the role of survival motor neuron protein in early development." Thesis, University of Aberdeen, 2017. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=237002.

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Spinal Muscular Atrophy (SMA) is caused by mutation or deletion of the Survival Motor Neuron 1 (SMN1), which encodes cell-ubiquitous SMN protein. Although classified as a neuromuscular disease, a range of systemic pathologies is reported in SMA patients. Despite a clear understanding of the genetics, the role of SMN protein in SMA pathogenesis is somewhat unclear, especially in tissues outside the CNS. Here, we describe failed liver development in response to reduced SMN levels, in a Taiwanese mouse model of severe SMA. Molecular analysis revealed significant changes in proteins involved in cell cycling and blood homeostasis including coagulation prior to motor neuron pathology. With SMN being directly associated with some of these proteins, this indicates primary liver pathology in SMA. Study of livers obtained from two other mouse models of SMA; severe SMNΔ7 and intermediate 2B, which have slightly higher SMN levels than Taiwanese SMA mice, also revealed significant overlapping pathologies, suggestive of high intrinsic susceptibility of the liver to SMN decrease. Proteomic study of pre-symptomatic 2B/- liver revealed significant perturbations in mitochondrial bioenergetics, which could account for metabolic defects in SMA patients. Vascular changes can be observed in mouse models of SMA and even skeletal muscle of severe SMA patients. Although Taiwanese SMA liver showed no morphological changes to its vasculature, it does have impairments in several key vascular signaling molecules, including VEGF and Tie-2. Furthermore, we report for the first time significant vascular changes in a zebrafish model of SMA, that could be associated with defective neuronal-vascular signaling and is supported by preliminary findings in the Taiwanese SMA retina. This thesis uncovers perturbations in several clinically relevant signalling pathways directly linked to SMN decrease, independent of the motor neurone pathology. Taken together this work emphasises the importance of a systemic therapy in SMA.

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Mello, Tayana Bezerra Teixeira. "Fibrinogenio, FVII, FVIII, FIX, FX e FXI como fatores de risco para tromboembolismo venoso em pacientes de uma população brasileira." [s.n.], 2006. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310151.

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Orientador: Joyce Maria Annichinno-Bizzacchi
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-08T02:29:39Z (GMT). No. of bitstreams: 1 Mello_TayanaBezerraTeixeira_D.pdf: 2343820 bytes, checksum: be3d8e4b057cd84ec6771c67b8b1407d (MD5) Previous issue date: 2006
Resumo: Nos últimos anos tem sido demonstrada uma associação entre níveis elevados de certos fatores da coagulação e risco de tromboembolismo venoso (TEV). Entretanto, o número de estudos é pequeno e a maioria estão restritos a populações caucasóides. Neste estudo caso-controle emparelhado por idade, sexo e etnia investigamos os níveis plasmáticos do fibrinogênio, FVII, FVIII, FIX, FX, FXI, FvW e grupo sanguíneo (GS) ABO no risco trombótico. Foram analisados 175 pacientes com TEV (122 mulheres e 53 homens), com idade mediana de 36 anos (13-63), acompanhados no Ambulatório de Hemostasia da Unicamp no período de julho de 2002 a julho de 2005. Na análise univariada, níveis elevados de FVIII (OR: 5,3 IC95% 2,9-9,6), FvW (OR: 4,9 IC95% 2,7-8,9), FIX (OR: 2,4 IC95% 1,3-4,4), FXI (OR: 2,1 IC95% 1,1-4,0) e GS não O (OR: 3,0 IC95% 1,9-4,6) foram fatores de risco para TEV. O FVIII, FvW e GS não O foram associados ao risco tanto em membro inferior como em sítio incomum da doença. A análise de todas estas variáveis, segundo critério de seleção ¿stepwise¿, mostrou o FVIII (OR: 3,1 IC95% 1,6-6,0), FvW (OR:2,8 IC95% 1,4-5,4) e o GS não-O (OR:2,2 IC95% 1,3-3,5) como fatores de risco independentes para TEV e que o FIX e FXI agiram sinergicamente a estas variáveis no acréscimo do risco trombótico. Risco de recorrência foi conferido por elevações do FIX (OR: 4,7 IC95% 1,8-11,9) e FXI (OR: 3,4 IC95% 1,8-8,7). Os determinantes dos níveis plasmáticos do FVIII não estão totalmente esclarecidos. Como a LRP (Low density lipoprotein receptor related protein) tem um papel no catabolismo do FVIII, foram pesquisados os polimorfimos C200T, o A775P e o D2080N no gene codificador dessa proteína, como fator de risco para TEV e a influência dos mesmos sobre os níveis do FVIII e FvW. Não houve diferença nas prevalências destes polimorfismos entre pacientes e controles. No entanto, no grupo-controle, o genótipo DN, do polimorfismo D2080N, foi associado a menores concentrações do FVIII (77,4 UI/dl) e FvW (70,2 UI/dl), quando comparado ao genótipo DD (127 UI/dl e 108,4 UI/dl, respectivamente p<0,05). Em conclusão, nesta população brasileira miscigenada, o FVIII, FvW , FIX, FXI e GS não O foram associados ao risco de TEV e o polimorfismo D2080N, no gene da LRP, interferiu com os níveis plasmáticos de FVIII e FvW
Abstract: During the last years an association between high levels of certain coagulation factors and the risk for venous thromboembolism (VTE) has been demonstrated. The number of studies, however, is small, and most of them are restricted to Caucasian populations. In this case control study, matched for age, sex and ethnicity, we investigated the plasma levels of fibrinogen, FVII, FVIII, FIX, FX, FXI, vWF and the ABO blood group (BG) in the thrombotic risk. It was analyzed 175 patients with VTE (122 women and 53 men), median age 36 years (13-63), followed at the hemostasis outpatient clinic at the State University of Campinas ¿ UNICAMP, between July 2002 and July 2005. In univariate analysis, elevated levels of FVIII (OR: 5.3 95%CI 2.9-9.6), FvW (OR: 4.9 95%CI 2.7-8.9), FIX (OR: 2.4 95%CI 1.3-4.4), FXI (OR: 2.1 95%CI 1.1-4.0) and non O BG (OR: 3.0 95%CI 1.9-4.6) were risk factors for VTE. FVIII, FvW and non O BG were associated with the risk both in lower limbs and unusual sites of disease. Analysis of all these variables by stepwise selection criteria showed FVIII (OR:3.1 95%CI 1.6-6.0), FvW (OR:2.8 95%CI 1.4-5.4) and non O BG (OR:2.2 95%CI 1.3-3.5) as independent risk factors for VTE, and FIX and FXI increased synergistically the risk of thrombosis of these variables. Risk of recurrence was conferred by FIX (OR:4.7 IC95% 1.8-11.9) and FXI (OR:3.4 IC95% 1.8-8.7). The FVIII plasma levels determinants are not well established. Since LRP (Low density lipoprotein receptor related protein) has a role in the catabolism of FVIII, we evaluated the C200T, A775P and, D2080N polymorphisms in the gene coding of this protein, as risk factor for VTE and their influence upon the levels of FVIII and vWF. There was no difference regarding the prevalence of these polymorphisms between patients and controls. However, in the control group, the DN genotype, of the D2080N polymorphism, was associated with lower concentrations of FVIII (77.4 UI/dl) and vWF (70.2 UI/dl), when compared to DD genotype (127 UI/dl e 108.4 UI/dl, respectively p<0.05). In conclusion, in these Brazilian miscigenous population, increased levels of FVIII, FvW, FIX, FXI and non O BG were associated with VTE risk and the D2080N polymorphism, in the LRP gene, influenced plasma levels of FVIII and vWF
Doutorado
Biologia Estrutural, Celular, Molecular e do Desenvolvimento
Doutor em Fisiopatologia Medica

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Le, Bonniec Bernard. "Contribution à l'études des sérine protéases de la coagulation et de la fibrinolyse." Paris 6, 1986. http://www.theses.fr/1986PA066414.

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Noubouossie, Fondjie-Denis. "Contribution du test de génération de thrombine in vitro à l'étude des troubles de la coagulation dans le drépanocytose." Doctoral thesis, Universite Libre de Bruxelles, 2013. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209459.

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La drépanocytose est associée à un état d’hypercoagulabilité qui se manifeste sur le plan clinique par un risque augmenté de thromboses artérielles et veineuses. L’exploration de la coagulation chez les patients drépanocytaires montrait surtout une activation de la coagulation et des altérations des acteurs pro- et anticoagulants du système hémostatique. Les tests de coagulation globale de routine tels que l’aPTT et le PT sont peu sensibles aux états d’hypercoagulabilité. La fonction hémostatique globale des patients drépanocytaires était donc peu connue. Le test de génération de thrombine est un test de coagulation globale, sensible aux états d’hypo- et d’hypercoagulabilité, facile à réaliser de nos jours avec une bonne reproductibilité. Nous l’avons utilisé pour démontrer que la coagulation globale des enfants drépanocytaires était caractérisée par une accélération des réactions de formation de la thrombine et par une augmentation du potentiel de thrombine endogène. Nous avons par la suite montré que les taux élevés de microparticules pro-coagulantes et du facteur VIII chez les enfants drépanocytaires seraient les facteurs déterminant l’accélération des réactions de formation de thrombine tandis que la réduction de l’activité anticoagulante du système protéine C / protéine S serait le facteur déterminant l’augmentation du potentiel de thrombine endogène. Les marqueurs de l’hémolyse corrélaient significativement avec ces facteurs ainsi qu’avec les paramètres de génération de thrombine, suggérant que l’hémolyse serait le mécanisme pathologique à la base de l’augmentation du potentiel de génération de thrombine chez les enfants drépanocytaires. Les paramètres de génération de thrombine n’étaient pas significativement différents entre l’état de stabilité clinique et l’état de crise vaso-occlusive. Chez les enfants hétérozygotes composites, ces paramètres avaient des valeurs intermédiaires entre celles des enfants contrôles et celles des enfants drépanocytaires homozygotes. Près de 40 % des enfants drépanocytaires homozygotes avaient un potentiel hémostatique supérieur à la moyenne + 2DS des enfants contrôles du même âge. Ces enfants présentant une génération de thrombine élevée se distinguaient des autres par leur plus jeune âge, une plus grande intensité de l’hémolyse, une plus courte durée de traitement par l’hydroxyurée et des vélocités du flux sanguin au doppler transcrânien plus élevées. Ces données suggèrent davantage un lien entre le potentiel de génération de thrombine et la vasculopathie cérébrale chez les enfants drépanocytaires. L’analyse de 4 enfants ayant reçu une greffe de cellules souches hématopoïétiques montrait une tendance à la réduction du potentiel de génération de thrombine et des autres altérations de la coagulation trois mois après la greffe. Le test de génération de thrombine permet une meilleure exploration de la coagulation globale des enfants drépanocytaires. Sa réalisation sur sang total permettrait une analyse plus globale en intégrant la participation des éléments figurés du sang particulièrement les globules rouges./

Sickle cell disease is associated with a hypercoagulable state that express clinically by an increased risk of arterial and venous thrombosis. The exploration of coagulation in sickle cell patients showed mainly activation of coagulation and alterations pro-and anticoagulants actors of the hemostatic system. Routine global testing of coagulation such as the prothrombin time and the activated partial thromboplastin time are insensitive to hypercoagulable states. The overall hemostatic function in sickle cell disease was so little known. The thrombin generation test is a test of overall coagulation. It is sensitive to both hypo- and hypercoagulable states. It is easy to perform nowadays with good reproducibility. We used it to demonstrate that the overall coagulation of sickle cell disease children was characterized by an acceleration of the reactions of thrombin formation and an increase of the endogenous thrombin potential. We have subsequently shown that high levels of procoagulant microparticles and high levels of factor VIII in children with sickle cell disease are the factors determining the acceleration of reactions leading to thrombin formation. Our results also showed that the reduced activity of the protein C / S anticoagulant pathway is a determining factor of the increased endogenous thrombin potential in sickle cell children. Markers of hemolysis correlated significantly with these factors as well as the parameters of thrombin generation, suggesting that hemolysis is probably the pathological mechanism underlying the increased potential for thrombin generation in children with sickle cell disease. Nearly 40% of children with homozygous sickle cell disease had their hemostatic potential above the mean + 2SD that of controls children of the same age. These children with high thrombin generation differed from others by their younger age, greater intensity of hemolysis, a shorter duration of treatment with hydroxyurea. They also had higher velocity of blood flow using transcranial Doppler. These data further suggest a potential link between thrombin generation and cerebral vasculopathy in children with sickle cell disease. Analysis of four children who received hematopoietic stem cells transplantation showed a tendency towards a reversibility of thrombin generation and other alterations of coagulation three months after the transplant. Thrombin generation assay allows a better exploration of the global coagulation of sickle cell disease children. Its realization on whole blood would be a more comprehensive analysis as it would integrate the participation of blood cells particularly red blood cells.
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished

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22

Ellery, Paul E. R. "Expression and modulation of tissue factor and tissue factor pathway inhibitor in an endothelial cell based model." Curtin University of Technology, School of Biomedical Sciences, 2008. http://espace.library.curtin.edu.au:80/R/?func=dbin-jump-full&object_id=18719.

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Haemostasis is a complex physiological process involving cellular and plasma protein components that interact to keep the blood fluid under normal conditions and prevent blood loss after vessel injury by promoting clot formation. Primary haemostasis encompasses the activation and aggregation of platelets and is supported by secondary haemostasis, in which the coagulation factors of the plasma interact in a complex series of reactions. Secondary haemostasis is initiated by the exposure of tissue factor (TF) to the blood after vessel injury. TF forms a complex with activated factor VII (FVIIa), which in turn activates factor X (FXa) and ultimately results in fibrin formation. The TF-FVIIa complex and FXa are tightly regulated by tissue factor pathway inhibitor (TFPI), a trivalent Kunitz-type protease inhibitor. The endothelium, consisting of endothelial cells (ECs), constitutes the inner lining of all blood vessels. As such, it is in constant contact with the blood and plays a major role in haemostasis by synthesising and storing both pro- and anti- coagulant substances, including TF and TFPI. Release of TFPI from ECs is increased after exposure to both unfractionated and low molecular weight heparins, though the mechanisms are not clearly defined. TFPI circulates in plasma, predominantly bound to lipoproteins, though the effect of the three major lipoproteins [low density (LDL), very low density (VLDL) and high density (HDL)] on the release of TFPI from ECs is not well established. Furthermore, previous studies have not systematically investigated the effect of these lipoproteins on both TF and TFPI. The initial aim of this project was to establish assays for the measurement of TF activity and TFPI antigen to supplement the TFPI activity assay that is well established in our laboratory.
These assays were then used to determine the effects of heparin and the major lipoproteins on the expression of TF and the release of TFPI on/from ECs. Human umbilical vein endothelial cells (HUVECs) were used as the EC model because their collection and isolation is well established and they have biochemical and physiological properties representative of in vivo conditions. A TF activity assay, based on a previously published method, was successfully modified and validated for the measurement of cell surface TF (standard curve R2 = 0.997). Despite exhaustive attempts, adaptation of this assay for plasma TF was unsuccessful, raising doubts regarding the plasma fractionation procedure of the originally published assay [Fukuda, C., Iijima, K. and Nakamura, K. (1989). "Measuring tissue factor (factor III) activity in plasma." Clinical Chemistry 35(9): 1897â€1900]. A novel insect cell expression system was used to produce well defined recombinant TFPI standards for use in TFPI activity and antigen assays. For the first time, truncated TFPI variants, containing the first Kunitz domain only, the first and second Kunitz domains only, and the first through third Kunitz domains minus the carboxyl terminus, were successfully produced in insect cells, though the full length molecule was not. Possible reasons for this include codon bias, protein instability and/or the signal peptide used. An ELISA to measure TFPI antigen was designed using a monoclonal antiâ€TFPI antibody directed against the Nâ€terminus for protein capture and a polyclonal antiâ€ TFPI antibody for detection. The assay was successfully optimised (standard curve R2 = 0.978, intraâ€assay CV = 4.8%), however it produced inaccurate results (normal range = 498.7 Â± 156.3 ng/mL), probably due to the antibody combination used.
TF and TFPI activity assays were used to determine the effect of both unfractionated and low molecular weight heparins (UFH and LMWH, respectively) on the release of TFPI and the expression of TF from/on ECs. A significant increase in the secretion of functional TFPI from ECs due to heparin (0 U/ml vs 1 and 10 U/mL) was demonstrated only in the presence of serum (UFH: 9.0 mU/mL vs 18.3 and 18.4 mU/mL, p < 0.0001; LMWH: 8.8 mU/mL vs 13.3 and 21.4 mU/mL, p < 0.05), suggesting, for the first time, that a component of serum is required for the heparinâ€dependent release of TFPI. The effect of LDL, VLDL and HDL on the release of TFPI and the expression of TF from/on ECs was also investigated. All three lipoprotein fractions increased the secretion of functional TFPI after one hour incubation (LDL: 12.5 Î¼g/mL, p < 0.01; 25 Î¼g/mL, p < 0.05; VLDL: 50 Î¼g/mL, p < 0.01; HDL: 50 Î¼g/mL, p < 0.05). This is the first data to demonstrate a HDLâ€dependent increase in released TFPI. After 24 hours, both LDL and VLDL decreased levels of secreted functional TFPI (LDL: 25 Î¼g/mL, p < 0.01; 50 Î¼g/mL, p < 0.01; VLDL: 12.5 Î¼g/mL, p < 0.01), probably due to the oxidation and subsequent association of both lipoprotein species with TFPI. Surprisingly, both LDL and VLDL decreased cell surface TF, though this effect was not dose dependent. These results suggest that the major lipoproteins have a short term anticoagulant effect which is reversed in the longer term due to lipid oxidation. In summary, this thesis describes the successful adaptation of a chromogenic assay for the measurement of cell surface TF activity and the production of truncated TFPI variants.
Both will be used for the measurement of TF and TFPI, their association with thrombus formation and propagation, and investigations into potential therapeutic applications of TFPI. The results presented in this thesis extend the current knowledge on the expression and release of TF and TFPI on/from ECs by heparin, highlighting the importance of serum in the heparin dependent release of TFPI in vitro. Furthermore, it describes for the first time the effects of the major lipoprotein fractions on TFPI release and TF expression. The data support novel mechanisms by which LDL and VLDL are procoagulant, and HDL anticoagulant. This study provides a foundation for future research of the TF pathway in cellular models, which is critical in increasing the understanding of the pathogenesis and treatment of thrombotic disease. vitro. Furthermore, it describes for the first time the effects of the major lipoprotein fractions on TFPI release and TF expression. The data support novel mechanisms by which LDL and VLDL are procoagulant, and HDL anticoagulant. This study provides a foundation for future research of the TF pathway in cellular models, which is critical in increasing the understanding of the pathogenesis and treatment of thrombotic disease.

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James, Stefan. "Coagulation, Inflammation and Myocardial Dysfunction in Unstable Coronary Artery Disease and the Influence of Glycoprotein IIb/IIIa Inhibition and Low Molecular Weight Heparin." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3372.

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24

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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25

Perdomo, Joana L. "Mathematical Modeling of Blood Coagulation." Scholarship @ Claremont, 2016. https://scholarship.claremont.edu/hmc_theses/71.

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Blood coagulation is a series of biochemical reactions that take place to form a blood clot. Abnormalities in coagulation, such as under-clotting or over- clotting, can lead to significant blood loss, cardiac arrest, damage to vital organs, or even death. Thus, understanding quantitatively how blood coagulation works is important in informing clinical decisions about treating deficiencies and disorders. Quantifying blood coagulation is possible through mathematical modeling. This review presents different mathematical models that have been developed in the past 30 years to describe the biochemistry, biophysics, and clinical applications of blood coagulation research. This review includes the strengths and limitations of models, as well as suggestions for future work.

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Sowedan, Ahmed M. "Rheometrical study of blood coagulation." Thesis, Swansea University, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.678535.

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Tate, Geoffrey Michael. "The blood coagulation mechanism and hypercoagulability." Thesis, University of Leeds, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.281131.

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Tosenberger, Alen. "Blood flow modelling and applications to blood coagulation and atherosclerosis." Doctoral thesis, Institut Camille Jordan, CNRS UMR 5208, Université Claude Bernard Lyon 1, Université Claude Bernard Lyon 1, France, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/244806.

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Sarphie, Anna Frances. "Changes in blood coagulation associated with hyperlipidaemia." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.319009.

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Head, Denise Marie. "Pharmacological modulation of the blood coagulation cascade." Thesis, King's College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298832.

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Fung, Marion R. "Molecular genetics of blood coagulation factor X." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/28783.

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Thirty thousand colonies of a bovine liver cDNA library were screened with a mixture of synthetic oligodeoxyribonucleotides coding for bovine factor X. Five positive colonies were identified, and plasmid DNA was isolated. Cleavage with restriction endonucleases showed that these plasmids (designated pBXl-5) contained inserts of 1530 bp, 770 bp, 700 bp, 1100 bp and 930 bp. DNA sequence analysis of the plasmid with the largest insert (pBXl) confirmed that bovine factor X cDNAs had been cloned. The cDNA sequence predicts that factor X is synthesized as a single chain precursor in which the light and heavy chains of plasma factor X are linked by the dipeptide Arg-Arg. The cDNA sequence also predicts that factor X is synthesized with a preproleader peptide. It is proposed that at least five specific proteolytic events occur during the conversion of preprofactor X to plasma factor Xa. A human liver cDNA library was screened by colony hybridization with a bovine factor X cDNA probe. Three of the positive plasmids contained overlapping DNA that coded for most of human factor X mRNA. A second human liver cDNA library was screened by in situ hybridization with 32P-labeled human factor X cDNA clones obtained from the first screen. Several clones were isolated that contained longer inserts. DNA sequence analysis of these clones allowed the prediction of the amino acid sequence of the precursor form of human plasma factor X. From these studies, it is predicted that human factor X is synthesized as a single polypeptide chain precursor in which the light and heavy chains of plasma factor X are linked by the tripeptide Arg-Lys-Arg. The cDNA sequence also predicts that human factor X is synthesized as a preproprotein having an aminoterminal leader peptide of 40 amino acid residues. A comparison of the amino acid sequences of human and bovine factor X shows high sequence identity around the calcium- binding regions and catalytic regions but low sequence identity around the nonfunctional regions. A human genomic phage library was screened with a human factor X cDNA as a hybridization probe. Thirty-two overlapping phage clones were isolated. Characterization of six of these clones indicates that over 32 Kbp of contiguous sequence is represented. DNA sequence and restriction map analysis shows that the factor X gene is comprised of at least 8 exons and 7 introns. No clones representing the 5' untranslated region and the prepeptide of the leader sequence were identified. Two further genomic phage libraries and two libraries specific for the 5' region of the factor X gene were screened, but no 5' end clones were obtained. Restriction enzyme mapping and Southern blot analysis indicate that thus far, the human factor X gene maps to 24 Kbp of the human genome. Comparison of the factor X gene with other vitamin K-dependent blood coagulation factor genes reveals homologous exon organization. Within the blood coagulation serine proteases factor X, factor IX, factor VII, and protein C form a closely related gene family.
Medicine, Faculty of
Biochemistry and Molecular Biology, Department of
Graduate

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32

Ramström, Sofia. "The role of platelets in whole blood coagulation /." Linköping : Univ, 2003. http://www.bibl.liu.se/liupubl/disp/disp2003/med776s.pdf.

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Hobby, Deanna Jeanne. "A COMPARISON OF ACTIVATED PARTIAL THROMBOPLASTIN TIME OBTAINED BY TWO TECHNIQUES IN PATIENTS FOLLOWING PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY." Thesis, The University of Arizona, 1987. http://hdl.handle.net/10150/291339.

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A descriptive study was conducted to test the null hypothesis: There will be no statistically significant difference between serum activated partial thromboplastin time (aPTT) obtained by two methods; venipuncture and large bore femoral arterial catheter. The convenience sample consisted of seventeen adults who had undergone percutaneous transluminal coronary angioplasty (PTCA) for the treatment of coronary artery disease. After the PTCA procedure, patients returned to an intensive care unit with a femoral intra-arterial catheter in place. Seventeen pairs of serum samples were obtained; one by venipuncture and one through the femoral intra-arterial catheter. Prior to obtaining the sample from the femoral intra-arterial catheter, 6.0 milliliters (3 times the deadspace of the catheter) of blood was withdrawn and discarded. aPTT samples were analyzed. T-tests were used to compare the results. Findings revealed that there was no statistically significant difference in the aPTT value when drawn from venipuncture versus the femoral intra-arterial catheter.

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Gershom, Edwin S. "Herpesvirus mediated activation of coagulation and fibrinolytic proteins." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/38099.

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Vascular disease, a leading cause of death worldwide, is associated with multiple risk factors that include age, diet, lifestyle and genetics. Herpesviruses, highly prevalent in the general population, have also been linked to vascular disease. To investigate the molecular basis of this relationship, the interactions between virus surface proteins and host hemostatic plasma proteins, comprising both clot forming (coagulation) and clot dissolving (fibrinolytic) proteases, which can both contribute to vascular disease, were studied. Previously, our laboratory demonstrated that purified herpes simplex virus type-1 (HSV1) and -2 (HSV2) and cytomegalovirus (CMV) contain cell-derived tissue factor (TF) and anionic phospholipids (aPL). Independent of cells, TF and aPL with factor (F) VIIa (FVIIa) initiate the extrinsic pathway of coagulation, activate FX to FXa, and lead to thrombin generation. This thesis identified additional herpesvirus-mediated coagulation pathway(s) and also demonstrated herpesvirus-mediated fibrinolysis. In addition to TF, FVIII amplified HSV1-initiated coagulation through the intrinsic pathway. Alternatively, independent of TF, HSV1 initiated coagulation through the contact pathway, via FXII activation. The ability to exploit the extrinsic, intrinsic and contact pathway of coagulation should make herpesvirus infection a strong prothrombotic risk yet the clinical correlation to vascular disease is relatively weak. To explain the in vitro versus clinical discrepancy, virus-mediated fibrinolysis was evaluated. Purified herpesviruses accelerated tissue plasminogen activator (tPA)-dependent plasminogen (Pg) activation to plasmin (Pn), the primary fibrinolytic protease responsible for fibrin clot dissolution. This Pn generation was independent of the physiological cofactor fibrin. Cell-derived annexin 2 (A2), previously identified on the surface of CMV, is a known accelerator of tPA-dependent Pn generation. Although A2 was identified among several Pg binding partners associated with each herpesvirus, it was dispensable for Pn generation. Herpesvirus-mediated plasminogen activation enhanced fibrinolysis independent of exogenous tPA. The enhanced fibrinolysis may attenuate the prothrombotic risk of herpesviruses, as an independent predictor of vascular disease. Plasmin enhanced cell susceptibility to infection, a virus-survival advantage also known for thrombin, FVIIa and FXa. Overall, for herpesviruses and other enveloped viruses, a mechanism is suggested where the envelope constituents initiate the activation of both pro-coagulation and pro-fibrinolytic proteins, modulating host cell susceptibility to infection and contributing to vascular disease.

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35

Soons, Johannes Wilhelmus Pieter Hubertus. "Studies on the inhibition of blood coagulation factor XIa." Maastricht : Maastricht : Rijksuniversiteit Limburg ; University Library, Maastricht University [Host], 1987. http://arno.unimaas.nl/show.cgi?fid=5391.

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Nguyen, Vina, and Vina Nguyen. "Microfluidic Paper Analytic Device for Assessment of Blood Coagulation." Thesis, The University of Arizona, 2017. http://hdl.handle.net/10150/624139.

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Monitoring blood coagulation while a patient is on cardiopulmonary bypass (CPB) is critical in preventing clots from arising in the bypass machine and consequently being sent into the patient’s bloodstream. Current methods used to monitor blood coagulation such as Activated Clotting Time (ACT) yield results that do not correlate coagulation time to heparin or protamine dosage and will typically take at least 400 s to yield a result that is safe to initiate bypass. Microfluidic paper-based analytical devices (μPAD) are advanced sensors based on a wide range of recently developed techniques for complex analytical methods. In this research, a point-of-care (POC) sensor was developed based on techniques adapted from lateral flow and µPAD. The effects of varied dosages of heparin and protamine were observed using this POC µPAD and an accompanying Raspberry pi-based monitoring device. Paper microfluidic channels were printed on nitrocellulose paper with a wax pattern. Human whole blood was added to an absorbent fiber glass sample pad preloaded with known amount of heparin or protamine. By having this absorbent pad on the inlet of the channel, the blood sample is able to travel through the channel via capillary flow. Significantly different (p < 0.05) rates of flow between blood samples with different doses of heparin and protamine show that the device can monitor the extent of coagulation and patient-specific responses to each drug. Thus a low-cost device was built that monitors the extent of blood coagulation and allows for individualized dosing of heparin and protamine in as little at 20 s and no more than 180 s.

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37

He, Shu. "Hypercoagulation in preeclampsia : implications for maternal health and foetal growth /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3647-1/.

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Eriksson-Berg, Margita. "Hemostasis in middle-aged women with coronary heart disease /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-978-1/.

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39

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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40

Ruttmann, Thomas Gotthard. "The effect of in vitro haemodilution on coagulation." Master's thesis, University of Cape Town, 1996. http://hdl.handle.net/11427/26986.

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41

Oliveira, Daniella Gorete Lourenço de [UNESP]. "Purificação e caracterização de proteínas de venenos de serpentes que interferem na cascata de coagulação sanguínea." Universidade Estadual Paulista (UNESP), 2006. http://hdl.handle.net/11449/87536.

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Made available in DSpace on 2014-06-11T19:22:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-12-08Bitstream added on 2014-06-13T20:10:06Z : No. of bitstreams: 1 oliveira_dgl_me_sjrp.pdf: 2024541 bytes, checksum: 9e617f882421a4dd2f2cc715da6fb79f (MD5)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Toxins isolated from vemos have been used as molecular tools to understand many physiological processes. The enzymes isolated from the venoms of Crotalus and Bothrops species interfere with the control and balance of the hemostatic system (PEREZ et al., 1996) and thus, the determination of their structures is potentially very important. These enzymes are serine proteinases that are similar to tyrpsin in their specificity but are generally referred to as thrombin-like enzymes due to their ability to cleave fibrinogen. The principal aim of this project was to isolate and characterize snake venom poteins that inetefere with the control and regulation of the hemostatic system in quantities and purity required for structural studies. Gel filtration, ion-exchange and HPLC chromatographic techniques were used to isolate convulxin, crotoxin, giroxin and crotamine, the principle components from the venoms of Crotalus durissus collineatus and Crotalus durissus terrificus and the serine and metalo proteinases from the venom of Bothrops jararaca. The purity of the samples was evaluated by SDS-PAGE and the specific activity of the samples was determined. Crystallization experiments were then carried out.

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42

Goldenberg, Neil A. "Development of the clot formation and lysis (CloFAL) global assay and its application to the investigation of bleeding disorders in children and adults /." Connect to abstract via ProQuest. Full text is not available online, 2008. http://proquest.umi.com/pqdweb?did=1545571881&sid=1&Fmt=2&clientId=18952&RQT=309&VName=PQD.

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Thesis (Ph.D. in Clinical Science) -- University of Colorado Denver, 2008.
Typescript. Includes bibliographical references (leaves 136-146). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;

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43

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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44

Jones, D. W. "Factor XII and antiphospholipid antibodies." Thesis, University of Kent, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311229.

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45

Sargeant, Paul. "Calcium signalling in human platelets : stored-regulated calcium entry." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318268.

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46

Thomas, Stephen. "Antithrombotic agents under flow conditions." Thesis, Open University, 2003. http://oro.open.ac.uk/54153/.

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Haemostasis is the result of a fine balance of interactions between the endothelium, plasma proteins and blood cells under a wide range of flow rates. To mimic these conditions in vitro, a parallel plate flow chamber with human umbilical vein endothelial cells (HUVEC) or extracellular matrix (ECM) has been developed. A method to investigate thrombin generation (TG) in platelet rich defibrinated plasma was validated and used to investigate inhibition by two distinct classes of antithrombotic agents: anti-platelet antibodies and anticoagulants, including unfractionated heparin (UFH), low molecular weight heparin (LMWH) and hirudin. Increasing flow rates increased TG, which was higher in the presence of ECM than in the presence of HUVEC. All anti thrombotic agents investigated were less effective in the presence of ECM. The monoclonal anti-platelet glycoprotein (GP) lIb/IlIa antibody, RFGP56, partially inhibited TG under static or arterial flow conditions and was less effective under venous flow conditions. The monoclonal anti-platelet GP Iba antibody, RFGP37, did not inhibit TG under flow or static conditions. A combination of the two antibodies showed no further activity than RFGP56 alone. UFH, which has equal anti-factor Xa and anti-thrombin activity, was able to inhibit TG under static and flow conditions. On an anti-Xa unit basis, comparatively more LMWH (with a 10: 1 ratio of anti-factor Xa to anti-thrombin activity) was required to inhibit TG under static and venous conditions, but under arterial conditions LMWH was as effective as UFH. Hirudin, a thrombin specific inhibitor, was totally effective under static conditions, but was only able to inhibit up to 40 % ofTG under flow. This study shows that some anti-platelet agents can inhibit coagulation and this may contribute to their antithrombotic efficacy under certain flow conditions. Although both the anti-factor Xa and anti-thrombin activities of anticoagulants are effective, anti-factor Xa activity may play a more important inhibitory role under flow conditions.

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Matata, Bashir Mnene. "Blood response to biomaterials : in vitro and clinical investigation of the contact phase of blood coagulation." Thesis, University of Strathclyde, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297340.

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48

Jesting, Amalie. "Evaluation of prolonged surface activated coagulation time." Thesis, Malmö universitet, Fakulteten för hälsa och samhälle (HS), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-27144.

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Background: Blood coagulation is an essential defense mechanism to prevent bleeding. Disorders in the coagulation system can be severe and blood tests measuring the blood’s ability to coagulate are important. Activated partial thromboplastin time (APTT) is a blood test that measures blood coagulation time. An abnormal prolonged APTT can both be associated with a bleeding tendency or a risk of thrombosis. Additional blood tests are needed to discover the cause of a prolonged APTT. One potential test is the APTT mixing study, which can separate samples with and without inhibitors. The aim of this project is to investigate how the cause of a prolonged APTT is evaluated today and to examine if it is possible to indicate the cause of a prolonged APTT using the APTT mixing study performed on routine samples. The goal is to be able to indicate the cause of a prolonged APTT immediately when is it ﬁrst discovered. This will save time and help guide the physicians in their work with the patient. Methods: Retrospective data is used to examine how the cause of a prolonged APTT is evaluated today. Samples with known cause of prolonged APTT are used to establish a cut-oﬀ value for the APTT mixing study to indicate the cause of a prolonged APTT. The cut-oﬀ values are then tested using routine APTT samples. Pre-analytical variables relevant to APTT are also investigated. Results: Today, specialized departments request most special coagulation blood tests. The APTT mixing study can separate samples with and without inhibitors with 90% speciﬁcity and sensitivity using index of circulating anticoagulants cut-oﬀ value of 16.0. In regard to pre-analytical variables, the centrifugation force aﬀects the plasma platelet count but not APTT and sample storage has an aﬀect on APTT. Conclusion: The APTT mixing study can be implemented as an additional test to indicate the cause of a prolonged APTT on routine samples.

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Oliveira, Daniella Gorete Lourenço de. "Purificação e caracterização de proteínas de venenos de serpentes que interferem na cascata de coagulação sanguínea /." São José do Rio Preto : [s.n.], 2006. http://hdl.handle.net/11449/87536.

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Orientador: Raghuvir Krishnaswamy Arni
Banca: Adélia Cristina Oliveira Cintra
Banca: Patrick Jack Spencer
Abstract: Toxins isolated from vemos have been used as molecular tools to understand many physiological processes. The enzymes isolated from the venoms of Crotalus and Bothrops species interfere with the control and balance of the hemostatic system (PEREZ et al., 1996) and thus, the determination of their structures is potentially very important. These enzymes are serine proteinases that are similar to tyrpsin in their specificity but are generally referred to as thrombin-like enzymes due to their ability to cleave fibrinogen. The principal aim of this project was to isolate and characterize snake venom poteins that inetefere with the control and regulation of the hemostatic system in quantities and purity required for structural studies. Gel filtration, ion-exchange and HPLC chromatographic techniques were used to isolate convulxin, crotoxin, giroxin and crotamine, the principle components from the venoms of Crotalus durissus collineatus and Crotalus durissus terrificus and the serine and metalo proteinases from the venom of Bothrops jararaca. The purity of the samples was evaluated by SDS-PAGE and the specific activity of the samples was determined. Crystallization experiments were then carried out.
Mestre

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50

Ariëns, Robert Anton Sybrand. "The tissue factor pathway of blood coagulation in health and disease." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 1997. http://arno.unimaas.nl/show.cgi?fid=5931.

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Dissertations / Theses on the topic 'Proteins in blood coagulation'

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