Dissertations / Theses: 'Hemostasis'

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Keebaugh, Audrey Elizabeth. "Evaluation of hemostasis in hyperthyroid cats." Thesis, Virginia Tech, 2020. http://hdl.handle.net/10919/99376.

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Background: Hyperthyroid cats are predisposed to thrombus formation. The mechanism for thrombogenesis is currently unknown, but could be associated with altered hemostasis as seen in hyperthyroid humans. Objective: The purpose of this study was to evaluate markers of hemostasis in hyperthyroid cats compared to healthy cats, and in hyperthyroid cats before and after treatments with radioactive iodine (RIT). Methods: Twenty-five cats with hyperthyroidism and 13 healthy euthyroid cats > 8 years of age were studied. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, antithrombin (AT), D-dimers, thrombin-antithrombin complexes (TAT), von Willebrand Factor antigen (vWF:Ag), and activity of factors VIII and IX were measured. An echocardiogram was performed in all cats and healthy cats with abnormal echocardiograms were excluded. Measurements of hemostasis were evaluated again in 7 cats > 6 months after RIT and deemed to have restored euthyroid status. Results: There is a significant likelihood of being in hypercoagulable state based on hyperthyroid state (P = 0.019) and serum T4 level is significantly associated with predicating hypercoagulability (P = 0.043). Hyperthyroidism is associated with significantly higher median fibrinogen concentration (P < 0.0001), higher median AT activity (P < 0.0001), and higher median vWF:Ag level (P = 0.01) with all values decreasing significantly post-RIT. Fibrinogen and AT had a strong positive correlation with serum T4 value (r = 0.79; 95% CI 0.63 - 0.89 and r = 0.70; 95% CI 0.50 - 0.84, respectively). Presence of an abnormal echocardiogram in hyperthyroid cats was associated with a significantly higher median fibrinogen concentration (P = 0.03). Echocardiographic status did not have a significant impact on the remaining hemostatic markers in hyperthyroid cats. Conclusions: These results provide evidence of altered hemostasis and hypercoagulability in hyperthyroid cats that do not appear to be solely attributed to cardiac abnormalities. These differences of altered hemostasis resolved after radioiodine therapy, but further studies are warranted to determine if hypercoagulable state resolves. Master of Science In feline hyperthyroidism, there is a predisposition for thrombus formation. An alteration of hemostasis has been documented in hyperthyroid humans, but despite reports of thrombus formation in hyperthyroid cats, the underlying mechanism is currently unknown. Hyperthyroidism can lead to cardiac abnormalities that could possibly contribute thrombus formation, although thrombus formation has occurred in hyperthyroid cats without detected abnormalities. The goal of this study was to evaluate markers of hemostasis in hyperthyroid cats presenting for radioiodine therapy to evaluate for presence of hypercoagulability. Twenty-five hyperthyroid cats were evaluated with hemostasis panels and echocardiograms. The results were compared to a group of 13 healthy cats. Markers of hemostasis and echocardiograms in 7 hyperthyroid cats were also compared to results 6 months or greater post-radioiodine therapy. There was evidence of altered hemostasis and hypercoagulability in hyperthyroid cats. The alterations noted resolved after radioiodine therapy and do not appear to be solely attributed to cardiac abnormalities seen in hyperthyroid cats.

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Hormiga, Hernando Gonzalez [UNESP]. "Aplicação de diferentes pinças hemostáticas em veias de equinos: estudo morfológico." Universidade Estadual Paulista (UNESP), 2016. http://hdl.handle.net/11449/144581.

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Submitted by HERNANDO EMILIO GONZÁLEZ HORMIGA null (nanoarts@hotmail.com) on 2016-11-02T17:59:46Z No. of bitstreams: 1 Tese.pdf: 3610727 bytes, checksum: ae874ed160c53f81a6efc6c833a53bdc (MD5) Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-11-10T12:30:07Z (GMT) No. of bitstreams: 1 hormiga_heg_me_bit.pdf: 3610727 bytes, checksum: ae874ed160c53f81a6efc6c833a53bdc (MD5) Made available in DSpace on 2016-11-10T12:30:07Z (GMT). No. of bitstreams: 1 hormiga_heg_me_bit.pdf: 3610727 bytes, checksum: ae874ed160c53f81a6efc6c833a53bdc (MD5) Previous issue date: 2016-10-27 Foi realizada a avaliação morfológica e morfométrica da veia cefálica submetida à pinçamento de cinco equinos hígidos. Foram testadas as pinças hemostáticas: Diffenbach bulldog, De Bakey bulldog, Rochester reta e De Bakey com cremalheira. Após 15 minutos da aplicação das referidas pinças, foi realizada a flebectomia parcial e coletadas as amostras referentes a cada segmento do vaso pinçado e do segmento controle sem pinçamento. Das peças procedeu-se as preparações histológicas dos segmentos da veia nas colorações de Hematoxilina-Eosina e Tricrômio de Masson, os cortes histológicos foram avaliados por microscopia óptica. Foi realizada análise morfológica das veias, de forma qualitativa, utilizando para isto uma escala de avaliação de lesões vasculares após pinçamento; a avaliação morfométrica, quantificando em micrometros o achatamento produzido pelas pinças nas diferentes camadas vasculares. Em ambos os estudos, morfológico e morfométrico, as pinças com serrilhamento transversal e fechamento tipo cremalheira causaram as maiores alterações, observou se marcada vacuolização das células musculares e desarranjo na túnica media com perda marcada das células endoteliais da túnica intima do vaso estudado. Morphometric and morphologic evaluation of the cephalic vein of five healthy horses submitted to clamping was done. Hemostatic clamps tested were Dieffenbach bulldog, De Bakey bulldog, Rochester straight and De Bakey with ratchets. 15 minutes after mentioned clamps were applied partial phlebotomy was performed and histologic sections of the veins were prepared and stained with Hematoxylin-Eosin and Masson Trichrome, after the stained preparations were evaluated by light microscopy. A qualitative morphological analysis of the veins was performed using a rating scale of vascular lesions after clamping; the morphometric evaluation consisted in quantifying in micrometers the flattening produced by the hemostatic clamps in the different vascular beds. In both studies, morphologic and morphometric, hemostats with transverse serration and ratcheted mechanism caused major changes, pronounced vacuolization of the muscle cells, derangement of the medium tunic and marked loss of endothelial cells of the intima tunic was observed in the vessel studied.

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Gonçalves, Daniele Silvano. "Avaliação das alterações hemorrágicas e tromboembólicas em cães com doença renal crônica." Botucatu, 2016. http://hdl.handle.net/11449/134372.

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Orientador: Regina Kiomi Takahira Resumo: A doença renal crônica (DRC) acomete principalmente cães idosos e tem como característica principal a perda irreversível da função renal. A DRC em cães promove alterações metabólicas graves, caracterizadas frequentemente pela azotemia, hipoalbuminemia e anemia não regenerativa. Tanto a azotemia quanto a uremia predispõem a alterações hemostáticas que podem levar a quadros hemorrágicos. Além das disfunções plaquetárias, deficiência de anticoagulantes naturais e redução da fibrinólise são fatores que predispõem ao tromboembolismo. Este trabalho tem como objetivo avaliar as possíveis tendências hemorrágicas ou trombóticas em cães com DRC. Foram selecionados 20 cães saudáveis (grupo controle) com exames dentro da normalidade e 17 cães com DRC em estágios III ou IV classificados segundo a IRIS e a relação proteína/creatirina urinária maior que um (grupo DRC). As amostras de sangue para a realização da tromboelastometria (TEM), agregação plaquetária, tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPA) e concentração de fibrinogênio foram colhidas em momento único para ambos os grupos após os critérios de inclusão serem confirmados. A análise estatística foi realizada de acordo com a distribuição das variáveis, ao nível de 5% de significância. No presente estudo foi possível observar um estado de hipercoagulabilidade sanguínea nos cães com DRC. Na TEM com o ativador de via extrínseca, observou-se encurtamento no tempo de coagulação e do tempo de formação do coá... (Resumo completo, clicar acesso eletrônico abaixo) Abstract: Chronic kidney disease (CKD) affects mostly older dogs and its main characteristic is the irreversible loss of kidney function. CKD in dogs promotes serious metabolic alterations, often characterized by azotemia, hypoalbuminemia and non-regenerative anemia. Azotemia and uremia predispose the hemostatic abnormalities that can lead to hemorrhagic cases. In addition to platelet dysfunction, deficiency of natural anticoagulants and reduced fibrinolysis are factors that predispose to thromboembolism. This work aims to evaluate the possible bleeding or thrombotic tendencies in dogs with CKD. 20 healthy dogs were selected (control group) with tests within normal limits and 17 dogs with CKD in stages III or IV classified according to IRIS and urine protein to creatinine ratio greater than one (CKD group). Blood samples for the realization of thromboelastometry (TEM), platelet aggregation, prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen concentration were collected at one time for both groups after the inclusion criteria had been confirmed. Statistical analysis performed according to the distribution of the variable at the 5% level of significance. In the present study, we observed a state of hypercoagulable blood in dogs with CKD. In TEM with the extrinsic pathway activator, there was shortening of the clotting time and clot formation time, increasing the alpha angle and the maximum clot firmness, and reducing the maximum lysis in dogs with CKD comp... (Complete abstract click electronic access below) Mestre

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Joesph, Wiencek R. "Regulating Hemostasis: The Factor Va Cofactor Effect." Cleveland State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=csu1431514489.

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Lindfelt, Jan O. W. "Hepatic nerves in hemostasis and glucose metabolism :." Lund : Dept. of Surgery, Lund University, 1993. http://catalog.hathitrust.org/api/volumes/oclc/39654187.html.

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Peterle, Daniele. "Molecular Mechanism in the Alteration of Hemostasis." Doctoral thesis, Università degli studi di Padova, 2018. http://hdl.handle.net/11577/3426350.

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Hemostasis is a finely tuned physiological process that, through the concerted action of several blood cells and proteins, maintains the integrity of the vascular system. This stepwise process begins after a vessel wall injury and includes: an initial vasospasm, a platelet plug formation (primary hemostasis), an assembly and activation of the coagulation factors that results in fibrin deposition at the site of injury (secondary hemostasis), and a final dissolution of the fibrin clot that restores the blood vessel patency (fibrinolysis) (Chapter 1). Alterations affecting one or more of these delicate processes lead to a large number of pathological manifestations, commonly referred to as cardiovascular diseases (CVD). Nowadays, CVD are the major cause of mortality and morbidity worldwide. Despite the social and economic burden of CVD, the currently available pharmaceutical repertoire is relatively limited to a few classes of molecules (heparins, platelet antiaggregants, vitamin-K antagonists, direct thrombin inhibitors) which, however, display important side effects and need to be employed with careful dose adjustments. These difficulties stem primarily from: i) the intrinsically complex nature of the procoagulant and anticoagulant biochemical mechanisms leading to physiological hemostasis, which renders external intervention very risky and unpredictable; ii) the inadequate knowledge of the biochemical mechanisms linking blood coagulation to other vital physio-pathological processes. The general aim of this Ph.D. project was to investigate some of the molecular mechanisms underlying hemostatic disorders. To address this relevant question, we proceeded by studying selected pathologies for which association with hemostatic complications has either been long-established (i.e., Antiphospholipid Syndrome (APS), infectious diseases) or has just been hypothesized (Parkinson’s disease (PD), Transthyretin-related Amyloidosis (ATTR)), focusing our attention on the physio-pathological proteins involved in the onset of these disorders. In a first stage, our attention was focused on the study of novel interactions between α-thrombin (αT), the key enzyme of the coagulation cascade, with other plasma proteins (i.e., β2-glycoprotein-I, α-synuclein). In a second stage, we investigated an alternative mechanism of activation of prothrombin, the precursor of αT, by a bacterial protease (subtilisin from B. subtilis). Finally, some selected proteases were tested against human transthyretin, whose proteolyzed form is a key factor in the onset of ATTR. In its traditional pathway, blood coagulation culminates with the FXa-mediated conversion of prothrombin zymogen into active αT, through the formation of the prothrombinase complex on the platelet surface. Mature αT is a 36.7 kDa serine protease with a chymotrypsin-like fold. αT plays a pivotal role in blood coagulation, being able to exert both procoagulant (platelets aggregation, fibrin generation) and anticoagulant (protein C activation) functions. The equilibrium between such different activities is regulated by the interaction of αT with other proteins through its active site and two positively charged regions, called exosites (exosite I and exosite II), which flank the catalytic cleft. In addition, αT is a multifunctional protease that, beyond blood coagulation, plays important roles also in other physiological processes such as inflammation, innate immune system, and nervous systems. In Chapter 2 we mapped the interaction between αT and β2-Glycoprotein I (β2GpI). β2GpI is a heavily glycosylated 45 kDa protein that resides in human plasma at a physiological concentration of 4 µM (0.25 mg/ml). Since the early 90's, β2GpI has been identified as the major autoantigen in the antiphospholipid syndrome (APS), a severe autoimmune disease clinically characterized by hemostatic alterations such as venous and arterial thrombosis, fetal loss and thrombocytopenia. Despite its involvement in the pathogenesis of APS, the physiological roles of β2GpI remain unclear and both pro- and anti-coagulant functions have been reported for this protein. In a recent work, we have shown that β2GpI selectively inhibits the procoagulant functions of human α-thrombin (i.e. prolongs fibrin clotting time, tc, and inhibits α-thrombin-induced platelets aggregation) without affecting the unique anticoagulant activity of the protease (i.e. the proteolytic generation of the anticoagulant protein C). Here, combining molecular modeling with biochemical/biophysical techniques, we provided a coherent structural model of αT-β2GpI complex. The model has allowed us to understand at the molecular level our previous in vitro results. In particular, our findings suggested that β2GpI may function as an anticoagulant protein, acting as a scavenger of αT for the binding to GpIbα receptor, thus impairing platelets aggregation while enabling normal cleavage of fibrinogen and protein C. Chapter 3 was dedicated to the role of bacterial proteases in inducing blood coagulation by direct proteolytic activation of prothrombin. This knowledge gap is particularly concerning, as bacterial infections are frequently complicated by severe coagulopathies, and, in about 35% of sepsis cases, by disseminated intravascular coagulopathies (DIC). Here, we show that addition of subtilisin (50 nM–2 µM), a serine protease secreted by the nonpathogenic bacterium Bacillus subtilis, to human plasma induces clotting by proteolytically converting prothrombin into active σPre2, a nicked Pre2 derivative with a single cleaved Ala470–Asn471 bond. Notably, we found that this non-canonical cleavage at Ala470–Asn471 is instrumental for the onset of catalytic activity in σPre2, which was however reduced of about 100-200 fold compared with natural αT. Of note, σPre2 could generate fibrin clots from fibrinogen, either in solution or in blood plasma, and could aggregate human platelets, either isolated or in whole blood. Our findings demonstrate that alternative cleavage of prothrombin by proteases, even by those secreted by non-virulent bacteria such as B. subtilis, can shift the delicate procoagulant-anticoagulant equilibrium toward thrombosis. The study object presented in Chapter 4 is the interplay between αT and α-synuclein (αSyn). αSyn is a small (14.6 kDa) presynaptic protein mainly synthesized in the brain and whose aggregation has been shown to trigger the onset of different neurodegenerative diseases, commonly referred to as synucleinopathies (i.e., Parkinson disease). As for β2GpI, the exact physiological role of αSyn is still elusive. Intriguingly, αSyn is also synthesized by platelets and was found to inhibit the Ca2+-dependent release of procoagulant α-granules after αT stimulation. Moreover, clinical evidences clearly indicate that patients affected by neurodegenerative disorders have lower risks of ischemic attack. The collateral effects of αSyn in the pathogenesis and its localization on platelet surfaces prompted us to investigate a possible role of it in the hemostatic system. Here, we studied the effects of αSyn on fibrin generation and platelet activation. Furthermore, we mapped the interaction sites on αSyn and αT. Briefly, our results indicate that the negatively charged C-terminal tail of αSyn binds to the electropositive exosite-2 of thrombin, thus impairing αT-mediated platelet activation in whole blood. At variance, αSyn does not alter the rate of fibrin generation, resulting only in a minor change in the ensuing fibrin structure. In Chapter 5 we attempted to correlate the onset of systemic transthyretin amyloidosis to an altered activation of blood coagulation. Human transthyretin (hTTR) is an abundant homo-tetrameric plasma protein (0.2 mg/ml) involved in the transport of thyroxine and retinol through the binding to retinol binding protein. Beyond its physiological roles, hTTR is known as an amyloidogenic protein whose aggregation is responsible for several amyloid diseases, including senile systemic amyloidosis (SSA), familial amyloid polyneuropathy (FAP), and familial amyloid cardiomyopathy (FAC). From a mechanistic point of view, the proteolytic cleavage of hTTR represents an important step in fibril formation. In particular, after cleavage around position 50, hTTR C-terminal fragments have been found to aggregate far more efficiently than the full-length hTTR. Nowadays, the protease(s) responsible for this cleavage is yet to be identified although it is predicted to be a serine protease with a trypsin-like fold. Since all coagulation factors are trypsin-like serine proteases, we decided to probe them for the proteolytic cleavage of hTTR. In addition, we also probed some selected bacterial proteases, as well as some digestive apparatus and immune system proteases. hTTR was resistant to all proteases tested except to subtilisin from B. subtilis, which was able to cleave hTTR at pH 7.4, generating in high yields the amyloidogenic fragment hTTR(59-127). Since the hTTR(59-127) fragment was identified in amyloid deposits, these new insights might have relevant implications in hTTR-based amyloidosis.

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Teixeira, Bruno Costa. "Efeito de diferentes intensidades de exercício aeróbio prévio, sobre a curva lipêmica, inflamação e hemostasia de sujeitos submetidos à refeição hiperlipídica." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/142537.

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Introdução: O consumo habitual de refeições ricas em gordura tem se mostrado indutor de doenças cardiovasculares (DCV), afetando o equilíbrio entre os sistemas de coagulação e fibrinólise e também induzindo o aumento de marcadores inflamatórios. Por outro lado, o exercício físico tem sido indicado como intervenção por atenuar o incremento da inflamação e equilibrar os sistemas hemostáticos em indivíduos que consomem uma refeição hiperlipídica (RH). Objetivo: Verificar o efeito subagudo de duas sessões com intensidades diferentes de exercício aeróbio na curva lipêmica, inflamação, hemostasia em sujeitos jovens saudáveis submetidos à refeição hiperlipídica. Metodologia: Onze sujeitos eutróficos do sexo masculino, fisicamente ativos, com idade média de 23 ± 3 anos participaram do estudo que foi composto por três protocolos com dois dias consecutivos cada. No dia 1 os sujeitos realizavam um dos três protocolos que era realizado de forma randomizada, os protocolos eram divididos em: exercício de baixa intensidade (BI), exercício de moderada intensidade (MI) e repouso (Con). No dia dois 12h após a realização do exercício prévio os sujeitos consumiam uma RH (15% proteínas, 35% carboidratos e 50% lipídeos). Foram realizadas coletas de sangue para analise de triglicerídeos (TG), Colesterol total (CT), lipoproteínas de alta densidade (HDL), lipoproteínas de baixa densidade (HDL) e Glicose, no basal (BS) e a cada hora de 1 à 5h após a RH. As coletas sanguíneas para análise de Ativador de plasminogênio (tPA), Inibidor do ativador de plasminogênio do tipo 1 (PAI-1), Fator de necrose tumoral alfa (TNFα), Interleucina 6 (IL-6) e Interleucina 10 (IL-10) foram realizadas no momento basal, 1h, 3h e 5h após a RH. Resultados: Os protocolos BI e MI apresentaram menor área abaixo da curva (AUC) de TG em relação ao Con (P<0,05). Houve diferença significativa no PAI-1 em relação ao BI quando comparado ao MI e Con e de tPA do protocolo BI em relação ao Con no momento 1h pós refeição (P<0,05). No FVII, os protocolos MI e BI foram significativamente menores que o Con no momento 1h pós RH (p<0,05). Houve diferença significativa em TNFα entre os protocolos MI e Con no momento 1h pós RH (P<0,05) e foram encontradas diferenças em IL-10 nos protocolos MI e Con nos momentos 1h e entre os protocolos MI e BI nos momentos 1h, 3h e 5h pós RH (P<0,05). Houve diferença em IL-6 em todos os momentos de todos os protocolos em relação ao momento basal (BS). Conclusão: A RH aumenta o estado inflamatório e desregula o equilíbrio entre coagulação e fibrinólise, o protocolo BI e MI atenuam a curva de TG em relação ao Con, o protocolo MI melhorou o estado inflamatório diminuindo TNFα e incrementado IL-10 e o protocolo BI melhorou a relação entre coagulação e fibrinólise atenuando a diminuição de tPA e diminuindo o incremento de PAI-1 e ambos os protocolos MI e BI não incrementaram FVII 1h após RH. Background: Regular consumption of high-fat meals has been considered to play a role in the development of cardiovascular diseases. The increase of postprandial lipemia after a high-fat meal consumption can imbalance the relationship between coagulation and fibrinolysis and, by consequence, enhance an inflammatory response. Conversely, exercise has been considered an important intervention, once it may attenuate inflammatory responses and counterbalance hemostatic systems during the postprandial period. Purpose: Verify the subacute effect of two exercise bouts performed at different intensities on postprandial lipemia, inflammation and hemostasis after the consumption of a high-fat meal. Methods: Eleven healthy and physically active male subjects with average age of 23 ± 3 years completed 2-day trials in three conditions: Control, low-intensity exercise (LI) and moderate-intensity exercise (MI). Subjects performed an exercise bout (LI or MI) or no exercise (Control) on the evening of day 1. On the morning of day 2, a high-fat meal was provided (15 % of protein, 35 % of carbohydrates and 50 % of lipids). Blood was sampled at fasting (0 h) and every hour from 1 to 5 h for triglycerides (TG), total cholesterol, HDL, LDL and glucose. For plasminogen activator inhibitor-1 (PAI-1), plasminogen activator (tPA), tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6) and interleukin-10 (IL- 10), blood was sampled at 0, 1, 3 and 5 h. Results: TG area under the curve (AUC) was lower in LI and MI than Control (P<0.05). For PAI-1, there was a difference from LI to MI and Control at 1 h (P<0.05). For tPA, there was a difference from LI to Control at 1 h (P<0.05). For FVII the protocols MI and BI there was difference from Con in at 1h. For TNFα, there was a difference from MI to Control at 1 h (P<0.05). IL-10 concentration was different from MI to Control at 1 h and from MI to LI at 1, 3 and 5 h (P<0.05). Fasting IL-6 concentrations were different between all conditions (P<0.05). Conclusion: The consumption of a high-fat meal increases the inflammatory process and deregulates the balance between coagulation and fibrinolysis. Exercise, independent of the intensity, can reduce TG AUC compared to Control. MI can reduce TNFα and increases IL-10, while LI regulates coagulation and fibrinolysis balance, which can be explained by the increase in tPA and increase in PAI-1.

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Boknäs, Niklas. "Studies on interfaces between primary and secondary hemostasis." Doctoral thesis, Linköpings universitet, Avdelningen för mikrobiologi och molekylär medicin, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-132413.

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Our conceptual understanding of hemostasis is still heavily influenced by outdated experimental models wherein the hemostatic activity of platelets and coagulation factors are understood and studied in isolation. Although perhaps convenient for researchers and clinicians, this reductionist view is negated by an ever increasing body of evidence pointing towards an intimate relationship between the two phases of hemostasis, marked by strong interdependence. In this thesis, I have focused on factual and proposed interfaces between primary and secondary hemostasis, and on how these interfaces can be studied. In my first project, we zoomed in on the mechanisms behind the well-known phenomenon of thrombin-induced platelet activation, an important event linking secondary to primary hemostasis. In our study, we examined how thrombin makes use of certain domains for high-affinity binding to substrates, called exosite I and II, to activate platelets via PAR4. We show that thrombin-induced platelet activation via PAR4 is critically dependent on exosite II, and that blockage of exosite II with different substances virtually eliminates PAR4 activation. Apart from providing new insights into the mechanisms by which thrombin activates PAR4, these results expand our knowledge of the antithrombotic actions of various endogenous proteins such as members of the serpin superfamily, which inhibit interactions with exosite II. Additionally, we show that inhibition of exosite II could be a feasible pharmacological strategy for achieving selective blockade of PAR4. In my second project, we examined the controversial issue of whether platelets can initiate the coagulation cascade by means of contact activation, a hypothesis which, if true, could provide a direct link between primary and secondary hemostasis. In contrast to previous results, our findings falsify this hypothesis, and show that some of the erroneous conclusions drawn from earlier studies can be explained by inappropriate experimental models unsuitable for the study of plateletcoagulation interfaces. My third project comprised an assessment of the methodological difficulties encountered when trying to measure the ability of platelets to initiate secondary hemostasis by the release of microparticles expressing tissue factor. Our study shows that the functional assays available for this purpose are highly susceptible to error caused by artificial contact activation. These results could help to improve the methodology of future research and thus pave the way for new insights into the roles of tissue factor-bearing microparticles in the pathophysiology of various thrombotic disorders. From a personal perspective, my PhD project has been a fascinating scientific odyssey into the largely unexplored interfaces between primary and secondary hemostasis. Looking forward, my ambition is to continue our work exploring platelet-coagulation interactions and to translate these insights into clinically meaningful information, which may someday improve the treatment of patients with bleeding and/or thrombosis.

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Kurdi, Mohamad. "Study of the clearance of proteins of hemostasis." Paris 7, 2011. http://www.theses.fr/2012PA077071.

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Le but de ce projet de thèse a été d'étudier la clairance de glycoprotéines jouant un rôle clé dans l'hémostase, le facteur X (FX) et le couple facteur Willebrand (FW)/facteur VIII (FVIII) qui circule dans le plasma sous forme de complexe non covalent. Dans la première partie de nos travaux, nous avons étudié l'implication des N-glycosylations du FX sur sa clairance. Il avait été préalablement établi par l'équipe que ces N-glycans influençaient la cinétique d'élimination du FX. Nous avons désormais établi qu'ils influencent également la biodistribution et les interactions cellulaires de la protéine. Ainsi, comparé au FX, un variant de FX N-déglycosylé interagit avec des types cellulaires différents au niveau du foie qui est l'organe principal de biodistribution de cette protéine. Le FX N-déglycosylé se lie et est dégradé par les hépatocytes. Quant au FX, il se lie aux cellules de Kupffer. Cette liaison du FX aux cellules de Kupffer semble d'ailleurs faire partie d'un mécanisme original protégeant le FX d'une clairance accélérée. Le FW et le FVIII sont des glycoprotéines dont les glycans sont fortement sialylés. Dans la deuxième partie de cette thèse, le rôle du récepteur Sialic acid-binding Ig-like lectin 5 (Siglec-5) dans la clairance du complexe FVIII/FW a été étudié. Siglec-5 est un récepteur présent à la surface des macrophages, type cellulaire dominant dans la clairance du complexe FVIII/FW. Nous avons montré que le FVIII et le FW peuvent se lier au Siglec-5. De plus, une surexpression de Siglec-5 in vivo est associée à une diminution des taux endogènes de FW et de FVIII. Ces résultats suggèrent que Siglec-5 joue un rôle dans le catabolisme du complexe FVIII/FW The main objective of this thesis was to study the clearance mechanisms of glycoproteins playing a key role in the hemostatic process, factor X (FX) and the factor VIII (FVIII)/von Willebrand factor (VWF) couple which circulates in plasma in a tight non-covalent complex. In the first part of our work, we have studied the involvement of FX N-glycosylations on its clearance. It had been previously established by the team that these N-glycans were important for the long half-life of FX. We have now extended these data by showing that N-glycosylations also influence organ biodistribution and cellular interactions of the protein. Indeed, as compared to FX, a N-deglycosylated FX variant interacts with different cell types in the liver which is the main target organ for FX biodistribution. N-deglycosylated FX binds to and is degraded by hepatocytes. Conversely, FX binds to Kupffer cells. The binding of FX to Kupffer cells appears to be part of an original mechanism protecting FX from an accelerated clearance. Both VWF and FVIII are glycoproteins whose glycans are capped with sialic acids. In the second part of this thesis, we have studied the role of a receptor, Sialic acid-binding Ig-like lectin 5 (Siglec-5), in the clearance of the FVIII/VWF complex. Siglec-5 is expressed on the surface of macrophages, a cell type that is dominant in the clearance of this complex. Our results showed that FVIII and FW are ligands for Siglec-5. Furthermore, overexpression of Siglec-5 in vivo is associated with decreased endogenous levels of the two glycoproteins. These results suggest that Siglec-5 can play a role in the catabolism of the FVIII/FW complex

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Shoffstall, Andrew J. "The Use of Synthetic Platelets to Augment Hemostasis." Case Western Reserve University School of Graduate Studies / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1363775111.

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Joshi, Smita. "CONTROLLING PLATELET SECRETION TO MODULATE HEMOSTASIS AND THROMBOSIS." UKnowledge, 2018. https://uknowledge.uky.edu/biochem_etds/37.

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Upon vascular injury, activated blood platelets fuse their granules to the plasma membrane and release cargo to regulate the vascular microenvironment, a dynamic process central to platelet function in many critical processes including hemostasis, thrombosis, immunity, wound healing, angiogenesis etc. This granule- plasma membrane fusion is mediated by a family of membrane proteins- Soluble N-ethyl maleimide Attachment Receptor Proteins(SNAREs). SNAREs that reside on vesicle (v-SNAREs) /Vesicle-Associated Membrane Proteins(VAMPs) interact with target/t-SNAREs forming a trans-bilayer complex that facilitates granule fusion. Though many components of exocytic machinery are identified, it is still not clear how it could be manipulated to prevent occlusive thrombosis without triggering bleeding. My work addresses this question by showing how the rates and extents of granule secretion could be regulated by various v-SNAREs. We also show that the granule cargo decondensation is an intermediate to secretion that also contributes to rates of cargo release. Platelets contain four major VAMP isoforms (-2, -3, -7, and -8), however, VAMP-8 and -7 play a primary role while VAMP-2 and -3 are ancillary in secretion. To exploit this heterogeneity in VAMP usage, platelet-specific V-2/3-/- and V-2/3/8-/- mouse models were generated and characterized to understand how secretion influences hemostasis. We found that each VAMP isoform differentially contributes by altering the rates and extents of cargo release. The loss of VAMP-2 and -3 had a minimal impact while the loss of VAMP-2, -3 and -8 significantly reduced the granule secretion. Platelet activation and aggregation were not affected though the spreading was reduced in V-2/3/8-/- platelets indicating the importance of secretion in spreading. Though coagulation pathways were unaltered, PS exposure was reduced in both V-2/3-/- and V-2/3/8-/- platelets suggesting diminished procoagulant activity. In vivo experiments showed that V-2/3/8-/- animals bled profusely upon tail transaction and failed to form occlusive thrombus upon arterial injury while V-2/3-/- animals did not display any hemostatic deficiency. These data suggest that about 40-50% reduction in secretion provides protection against thrombosis without compromising hemostasis and beyond 50% secretion deficiency, the animals fail to form functional thrombi and exhibit severe bleeding. Additionally, detailed structural analysis of activated platelets suggests that the post-stimulation cargo dissolution depends on an agonist concentration and stimulation duration. This process is VAMP-dependent and represents intermediate steps leading to a full exodus of cargo. Moreover, we also show that VAMP-8 is important for compound fusion events and regulates fusion pore size. This is a first comprehensive report that shows how manipulation of the exocytic machinery have an impact on secretion and ultimately on hemostasis. These animals will be instrumental in future investigations of platelet secretion in many other vascular processes.

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Assunção, Pedrita Carvalho Ferreira. "Tromboelastometria (ROTEM) em gatos da raça Maine Coon portadores e não portadores da mutação (A31P) no gene MYBPC3 para miocardiopatia hipertrófica." Botucatu, 2019. http://hdl.handle.net/11449/180649.

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Orientador: Regina Kiomi Takahira Resumo: A miocardiopatia hipertrófica é a doença cardíaca mais observada em gatos da raça Maine Coon e está diretamente relacionada à presença de uma mutação (A31P) que ocorre no gene da proteína C miosina ligante (MYBPC3). A doença pode provocar em determinados pacientes quadros secundários graves como o tromboembolismo arterial (TEA). O objetivo do presente trabalho foi avaliar gatos da raça Maine Coon não portadores da mutação A31P no gene MYBPC3 (G1) e portadores da mutação A31P no gene MYBPC3 (G2), por meio do perfil tromboelastométrico. Foram selecionados no estudo 15 gatos pertencentes ao grupo G1 e 15 gatos G2, previamente avaliados para A31P-MYBPC3, tendo como critério de inclusão a presença ou não da mutação e higidez clínica e laboratorial para hemograma e provas de bioquímicas séricas. A coleta das amostras ocorreu em momento único após avaliação ecocardiográfica. A análise estatística foi realizada por meio de análise descritiva dos dados seguida da comparação dos grupos ao nível de 5 % de significância. No presente estudo o perfil pela tromboelastometria (TEM) não identificou diferenças quando comparados os grupos G1 e G2, portanto os animais não demonstraram variações de coagulabilidade. A concentração sérica de albumina foi significativamente menor no G2, mas se manteve dentro dos intervalos de referência para a espécie. No ecocardiograma foi observada alteração no volume diastólico final no G2, indicando a presença de possível disfunção diastólica. O G2 também aprese... (Resumo completo, clicar acesso eletrônico abaixo) Abstract: Hypertrophic cardiomyopathy is the most observed heart disease in Maine Coon cats and is directly related to the presence of a mutation (A31P) occurring in the myosin binding protein C (MYBPC3) gene. The disease can cause serious side effects such as arterial thromboembolism (ATE) in certain patients. The objective of the present study was to evaluate the thromboelastometric profile in cats Maine Coon breed without mutation A31P on MYBPC3 gene (G1) and mutation carrier (G2). Thirty cats previously evaluated for A31P-MYBPC3 were divided into G1 and G2 groups (n=15). The inclusion criteria were the presence or absence of mutation and clinical data, blood counts and serum biochemistry within reference intervals. The samples were taken at a single moment after an echocardiographic evaluation. Statistical analysis was performed through descriptive data analysis followed by comparison of groups at the 5% level of significance. In the present study, the profile by thromboelastometry (TEM) did not identify differences when comparing groups G1 and G2, and the animals showed no coagulability variations. Serum albumin concentration was significantly lower in the mutation carrier group (G2), but it remained within the reference intervals for the species. On the echocardiogram, a change in final diastolic volume was observed in the carrier group, indicating that the carrier animals should be evaluated to previous identification of possible diastolic dysfunction. The carrier group also pre... (Complete abstract click electronic access below) Doutor

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Hormiga, Hernando Gonzalez. "Aplicação de diferentes pinças hemostáticas em veias de equinos estudo morfológico /." Botucatu, 2016. http://hdl.handle.net/11449/144581.

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Orientador: Carlos Alberto Hussni Banca: Marcos Jun Watanabe Banca: Cláudia Helena Pellizzon Resumo: Foi realizada a avaliação morfológica e morfométrica da veia cefálica submetida à pinçamento de cinco equinos hígidos. Foram testadas as pinças hemostáticas: Diffenbach bulldog, De Bakey bulldog, Rochester reta e De Bakey com cremalheira. Após 15 minutos da aplicação das referidas pinças, foi realizada a flebectomia parcial e coletadas as amostras referentes a cada segmento do vaso pinçado e do segmento controle sem pinçamento. Das peças procedeu-se as preparações histológicas dos segmentos da veia nas colorações de Hematoxilina-Eosina e Tricrômio de Masson, os cortes histológicos foram avaliados por microscopia óptica. Foi realizada análise morfológica das veias, de forma qualitativa, utilizando para isto uma escala de avaliação de lesões vasculares após pinçamento; a avaliação morfométrica, quantificando em micrometros o achatamento produzido pelas pinças nas diferentes camadas vasculares. Em ambos os estudos, morfológico e morfométrico, as pinças com serrilhamento transversal e fechamento tipo cremalheira causaram as maiores alterações, observou se marcada vacuolização das células musculares e desarranjo na túnica media com perda marcada das células endoteliais da túnica intima do vaso estudado. Abstract: Morphometric and morphologic evaluation of the cephalic vein of five healthy horses submitted to clamping was done. Hemostatic clamps tested were Dieffenbach bulldog, De Bakey bulldog, Rochester straight and De Bakey with ratchets. 15 minutes after mentioned clamps were applied partial phlebotomy was performed and histologic sections of the veins were prepared and stained with Hematoxylin-Eosin and Masson Trichrome, after the stained preparations were evaluated by light microscopy. A qualitative morphological analysis of the veins was performed using a rating scale of vascular lesions after clamping; the morphometric evaluation consisted in quantifying in micrometers the flattening produced by the hemostatic clamps in the different vascular beds. In both studies, morphologic and morphometric, hemostats with transverse serration and ratcheted mechanism caused major changes, pronounced vacuolization of the muscle cells, derangement of the medium tunic and marked loss of endothelial cells of the intima tunic was observed in the vessel studied. Mestre

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Hwang, Joo Ha. "Ultrasound-mediated vascular bioeffects : applications for hemostasis and sclerotherapy /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/7992.

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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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Maji, Debnath. "A Microfluidic Dielectric Sensor for Comprehensive Assessment of Hemostasis." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1579798937224898.

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PAVANI, Giulia. "The Endothelial Protein C Receptor enhances FVIIa mediated hemostasis." Doctoral thesis, Università degli studi di Ferrara, 2014. http://hdl.handle.net/11392/2388933.

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Recombinant activated human Factor VII (rFVIIa) is an established hemostatic agent in hemophilia but its mechanism of action remains unclear. Although tissue factor (TF) is its natural receptor, rFVIIa also interacts with the endothelial protein C receptor (EPCR) through its g-carboxyglutamic acid (Gla) domain with unknown hemostatic consequences in vivo. Here, we study whether EPCR facilitates rFVIIa hemostasis in hemophilia using a mouse model system. Murine activated FVII (mFVIIa) is functionally homologous to rFVIIa, but binds poorly to murine EPCR (mEPCR). We modified mFVIIa to gain mEPCR binding using 3 amino acid changes in its Gla-domain. The resulting molecule mFVIIa-FMR specifically bound mEPCR in vitro and in vivo and was identical to mFVIIa with respect to TF affinity and procoagulant functions. Using two macrovascular injury models in hemophilic mice, administered mFVIIa-FMR exhibited superior hemostatic properties compared to mFVIIa. These effects were specific to the mFVIIa- FMR and mEPCR interaction since antibody blocking of mEPCR abolished them. Since mFVIIa-FMR models both the TF-dependent as well as EPCR binding properties of rFVIIa, our data unmask a novel contribution of EPCR on the action of rFVIIa administration in hemophilia. This may prompt the rational design of improved and safer rFVIIa therapeutics.

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Сабадаш, В. Є., Є. Є. Сабадаш, Т. В. Сисойкіна, Т. О. Дядічева, А. В. Сігова, Л. П. Випріцька та Л. С. Долженко. "Стан тромбоцитарного гемостазу у хворих на хозл з хронічним легеневим серцем в динаміці лікування антиагрегантам". Thesis, Видавництво СумДУ, 2009. http://essuir.sumdu.edu.ua/handle/123456789/11106.

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Hoore, Masoud [Verfasser], Gerhard [Gutachter] Gompper, and Krug [Gutachter] Joachim. "Modeling Primary Hemostasis / Masoud Hoore ; Gutachter: Gerhard Gompper, Krug Joachim." Köln : Universitäts- und Stadtbibliothek Köln, 2018. http://d-nb.info/1161223282/34.

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Batista, Saulo Hilton Botelho. "Evaluation of the use of different local hemostatics procedures to manage post extraction bleeding in patients under anticoagulation treatment." Universidade Federal do CearÃ, 2010. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=6328.

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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior The therapeutic use of Varfarin, the most common oral anticoagulant it is indicated in many cases, including the atrial fibrillation, cardiac valvular prostheses and venous trombolic disease. Many discussions still exist related to the suspension or not before tooth extraction. People who are for itâs suspension agree that it may increase the risk of hemorrhage, however the ones who prefer to maintain itâs use refer the high risk of tromboembolism. Due to the controversy related to the cronic use of oral anticoagulant before tooth extraction and what to use to control bleeding after extraction, we decided to perform a one center randomized clinical trial study to compare the effectiveness of the hemostasis using soaked gauze with tranexamic acid at 4,8% and plain gauze and the use of collagen sponge (HemosponÂ), using it inside the tooth socket after extraction. The sample was made of 84 surgical procedures performed in 38 patients who were under anticoagulant treatment and who needed at least one tooth extraction. The trial was divided in three groups regarding the method used to reach hemostasis after tooth extraction. In group I we used compression with soaked gauze with tranexamic acid at 4,8%; in group II we used collagen sponge (HemosponÂ) inside the socket while in group III we compressed the socket with dry gauze for 8 minutes. There were two cases of post surgical bleeding, being one from group I and one from group II. The data collected was evaluated thru SPSS 1.5 (Statistic Package of Social Science) program. All the statistical analysis performed were considered significantly when p was less than 5%. We used the Qui square X2 Test, Fisher Exact Test e Analysis of Variance (ANOVA) to verify the variables of the data. There was no statistically significant difference between the groups, related to bleeding (p>0,05). The compression with dry gauze and suture, compression with soaked gauze with trenaxamic acid at 4.8% and suture and the use of collagen sponge (HemosponÂ) in the tooth socket hold with suture showed similar efficacy to the control of post extraction bleeding in patients who are under anticoagulant treatment. A terapÃutica com varfarina, o anticoagulante oral mais utilizado, estÃ indicada em mÃltiplas situaÃÃes, incluindo a fibrilaÃÃo atrial, prÃteses valvulares cardÃacas e o tromboembolismo venoso. DiscussÃes ainda existem sobre a indicaÃÃo ou nÃo da sua interrupÃÃo prÃvia a realizaÃÃo de exodontias. Aqueles que defendem a parada de sua administraÃÃo baseiam tal decisÃo no risco aumentado de hemorragias, enquanto os que acreditam na manutenÃÃo da terapia ressaltam o risco de tromboembolismo. Em virtude das controvÃrsias acerca da realizaÃÃo de exodontias em pacientes que fazem uso crÃnico de anticoagulantes orais, alÃm da dÃvida de que mÃtodo empregar no controle do sangramento pÃs-exodontia, decidimos realizar um estudo do tipo ensaio clÃnico, unicÃntrico, randomizado com o objetivo de comparar a efetividade hemostÃtica local da compressÃo com gaze embebida ou nÃo em Ãcido tranexÃmico Ã 4,8% com o emprego da esponja de colÃgeno (HEMOSPONÂ) no interior do alvÃolo pÃs-exodontia. A amostra foi constituÃda por 84 procedimentos cirÃrgicos realizados em 38 pacientes sob terapia anticoagulante que necessitavam de pelo menos uma extraÃÃo dentÃria. A amostra foi dividida em trÃs grupos a depender do mÃtodo hemostÃtico local empregado para o controle do sangramento apÃs a extraÃÃo dentÃria. No grupo I utilizou-se a compressÃo com gaze embebida em Ãcido tranexÃmico a 4,8%; no grupo II introduziu-se no interior do alvÃolo uma esponja de colÃgeno (HemosponÂ); enquanto no grupo III, a compressÃo com gaze seca por 8 minutos foi o mÃtodo empregado. Em dois casos foi observado sangramento pÃs-operatÃrio sendo um paciente do grupo I e outro do grupo II. Os dados coletados foram consolidados e avaliados por meio do programa SPSS 15.0 (Statistic Package of Social Science). Todas as anÃlises estatÃsticas efetuadas foram consideradas significativas quando valor de p foi menor que 5%. Utilizou-se os testes Qui-Quadrado (XÂ), Teste Exato de Fisher e AnÃlise de VariÃncia (ANOVA) para verificar as diferenÃas entre as variÃveis. NÃo houve diferenÃa estatisticamente significante entre os grupos com relaÃÃo Ã ocorrÃncia de hemorragias (p-valor>0,05). A compressÃo com gaze seca associado Ã sutura, a compressÃo com gaze embebida com Ãcido tranexÃmico a 4,8% associada a sutura e o emprego da esponja de fibrina (HemosponÂ) intra-alveolar associado a sutura mostraram eficÃcia semelhante no controle do sangramento pÃs-exodontia em pacientes sob terapia anticoagulante.

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Espinosa, Sánchez Sebastián Antonio. "Evaluación de medidas hemostáticas locales postexodoncia bajo terapia anticoagulante oral mantenida en pacientes con INR bajo 4.0." Tesis, Universidad de Chile, 2004. http://www.repositorio.uchile.cl/handle/2250/110709.

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El manejo quirúrgico de pacientes bajo tratamiento anticoagulante oral ha estado por mucho tiempo determinado por la suspensión del fármaco 2 días antes del acto quirúrgico. La intención de este trabajo fue la de dejar en el pasado dicha metodología, manteniendo la terapia anticoagulante, realizando un examen de laboratorio previo para obtener el nivel de anticoagulación en que se encuentra el paciente y una vez realizada la exodoncia (no complicada), otorgar hemostasia con medios locales mecánicos. Según los resultados obtenidos, aparentemente sería un procedimiento seguro, tomando en cuenta que el único riesgo que se toma es el de un sangramiento post-operatorio, el cual puede ser controlado. Lo anterior es además corroborado por la literatura existente y permite al operador no enfrentar un posible evento Tromboembólico que pudiese ocurrir al suspender el tratamiento anticoagulante oral.

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Labuda, Cecille Pemberton. "Enhanced high intensity focused ultrasound heat deposition for more efficient hemostasis /." Full text available from ProQuest UM Digital Dissertations, 2008. http://0-proquest.umi.com.umiss.lib.olemiss.edu/pqdweb?index=0&did=1905744431&SrchMode=1&sid=8&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1279568381&clientId=22256.

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Thesis (Ph.D.)--University of Mississippi, 2008. Typescript. Vita. "May 2008." Major professor: Charles C. Church Includes bibliographical references (leaves 95-102). Also available online via ProQuest to authorized users.

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Druga, David A. "Feasibility of combat hemostasis methods in civilian prehospital emergency medical care." Thesis, Boston University, 2012. https://hdl.handle.net/2144/12353.

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Thesis (M.A.)--Boston University Uncontrolled hemorrhage is the leading cause of preventable traumatic death in both military and civilian populations. Hemorrhage often causes coagulopathy, which intensifies hemorrhage and complicates its treatment. The armed conflicts in Afghanistan and Iraq have allowed the military to test new hemostatic products and procedures in an effort to better control hemorrhage and reduce its associated morbidity and mortality rates. These methods were analyzed for efficacy and suitability in the civilian prehospital setting. Several invasive and non-invasive interventions were found to be beneficial. Despite centuries of controversy surrounding their use, emergency tourniquets can be safe, lifesaving tools for controlling severe extremity hemorrhage when adequate tourniquet designs are properly used. Hemostatic dressings are very useful as hemorrhage control adjuncts, and two products (Combat Gauze and Celox) are recommended for prehospital use based on their efficacy, mechanisms of action, ease of use, low cost, shelf-life, and other properties. Several pharmacological interventions were evaluated for prehospital use in addressing the anticoagulant and hyperfibrinolytic nature of trauma-associated coagulopathy. Recombinant activated Factor VII, commonly used in hemophiliac-related bleeding, does not improve outcomes in trauma patients. Tranexamic acid, which is commonly used to reduce bleeding in elective surgeries, has been demonstrated to significantly lower mortality in trauma patients with severe hemorrhage, especially when administered within three hours of injury. Recommendations were also made based on the results of military-developed damage control resuscitation protocols: restoration of perfusion is the best way to correct coagulopathy and prehospital fluid administration should be limited to restore perfusion and maintain systolic blood pressures of 80 to 90 mmHg. Hypothermia and hyperthermia are correlated with higher mortality in trauma patients, so temperature management was identified as a top priority in prehospital trauma care. Finally, the properties of stored blood were investigated in the setting of massive transfusion so that paramedics conducting interfacility transfers of these patients could be made aware of common complications to anticipate adverse events.

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Riescher-Tuczkiewicz, Alix. "Study of complex hemostasis in patients with cirrhosis : pathophysiology and management." Electronic Thesis or Diss., Université Paris Cité, 2024. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=7690&f=75939.

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La cirrhose est une maladie chronique du foie associée à des perturbations complexes de l'hémostase. Les patients atteints de cirrhose peuvent présenter des saignements, notamment après des gestes invasifs, qui sont associés à une morbi-mortalité élevée. Une meilleure compréhension de l'hémostase complexe des patients atteints de cirrhose et une meilleure prédiction des saignements post-procéduraux sont donc nécessaires pour améliorer la prise en charge de ces patients. L'objectif de mon travail était : (a) d'étudier deux acteurs de l'hémostase, la protéase nexine 1 (PN-1) et les vésicules extracellulaires (VE), dont le rôle dans l'équilibre hémostatique des patients atteints de cirrhose est inconnu ; (b) affiner la prédiction des hémorragies post-procédures invasives. Premièrement, j'ai mesuré par ELISA la concentration plasmatique de PN1 dans une cohorte prospective de patients atteints de cirrhose, tous stades confondus, chez qui les données cliniques, biologiques, hémodynamiques et radiologiques étaient disponibles ainsi que la survie à un an (« cohorte suivi»), et dans une cohorte prospective de patients atteints de cirrhose tous stades confondus qui ont eu un une biopsie hépatique (« cohorte PBH »). Dans la « cohorte suivi », la concentration de PN-1 était plus élevée dans le plasma des patients atteints de cirrhose comparée aux témoins sains et augmentait avec la gravité de la cirrhose. Les patients dont la concentration de PN-1 était supérieure au seuil défini par l'indice de Youden pour diagnostiquer le décès à un an avaient une incidence cumulée de décès à 1 an supérieure aux patients dont la concentration de PN1 était inférieure à ce seuil. Dans la « cohorte PBH », la concentration de PN-1 n'était pas associée à la survenue de saignements post-PBH. Une thromboélastométrie rotationnelle a été réalisée dans du plasma riche en plaquettes de patients atteints de cirrhose décompensée stable Child Pugh B/C, en présence ou non d'un anticorps bloquant la PN-1. Les résultats montraient que l'inhibition de la PN-1 induisaient une fibrinolyse plus précoce. Deuxièmement, j'ai regardé l'impact des VE sur la coagulation en réalisant des tests de génération de thrombine sur du plasma avec VE et sans VE (retirées par ultracentrifugation), provenant de patients atteints de cirrhose (tous stades de sévérité). J'ai constaté que le retrait des VE du plasma de patients atteints de cirrhose avait peu d'impact sur la génération de thrombine alors que l'impact était fort avec le plasma de témoins sains, suggérant que leur rôle était moindre dans la coagulation dans la cirrhose. Troisièmement, afin d'améliorer la prédiction des saignements post-procéduraux, j'ai (i) étudié l'intérêt d'un bilan d'hémostase exhaustif chez 302 patients atteints de cirrhose et j'ai constaté que celui-ci n'améliorait pas la prédiction des saignements ; (ii) interrogé 52 experts internationaux sur le risque de saignement associé aux procédures invasives. Les résultats ont permis d'établir un consensus pour 52 procédures invasives, 17 étant classées à haut risque de saignement et 35 à bas risque et également de définir des seuils de tests d'hémostase (plaquettes, INR, TCA, fibrinogène) permettant de réaliser une procédure invasive en toute sécurité. En conclusion, mes résultats montrent que, par rapport aux individus sains, l'hémostase des malades atteints de cirrhose est caractérisée par (a) une augmentation de la concentration circulante de PN-1 ; (b) un rôle de PN-1 dans la fibrinolyse puisqu'elle inhibe une fibrinolyse excessive ; (c) une perte du rôle des VEs dans la génération de thrombine. D'un point de vue pratique, ni les tests d'hémostase globaux ni la concentration circulante de PN-1 ne permettent de prédire la survenue de saignement post-PBH. Le consensus d'expert que j'ai obtenu permet de classer les procédures invasives pour affiner les futures études et guider la prise de décision clinique Cirrhosis is a chronic liver disease associated with complex disturbances of hemostasis. Patients with cirrhosis may experience bleeding, particularly after invasive procedures, which is associated with high morbidity and mortality. A better understanding of the complex hemostasis of patients with cirrhosis and better prediction of post-procedural bleeding are therefore needed to improve the management of these patients. The aim of my work was: (a) to study two players in hemostasis, the protease nexin 1 (PN-1) and extracellular vesicles (EVs), whose role in the hemostatic balance of patients with cirrhosis is unknown; (b) to refine the prediction of invasive post-procedural bleeding. Firstly, I measured plasma PN1 concentration by ELISA in a prospective cohort of patients with cirrhosis of all stages for whom clinical, biological, hemodynamic and radiological data were available, as well as one-year survival ("outcome cohort"), and in a prospective cohort of patients with cirrhosis of all stages who underwent liver biopsy ("LB cohort").In the "outcome cohort", the concentration of PN-1 was higher in the plasma of patients with cirrhosis compared with healthy controls, and increased with the severity of cirrhosis. Patients whose PN-1 concentration was above the threshold defined by the Youden index for diagnosing death at 1 year had a higher cumulative incidence of death at 1 year than patients whose PN1 concentration was below this threshold. In the "LB cohort", PN-1 concentration was not associated with the occurrence of post-LB bleeding. Rotational thromboelastometry was performed in platelet-rich plasma from patients with stable decompensated Child Pugh B/C cirrhosis, in the presence or absence of a PN-1-blocking antibody. The results showed that PN-1 inhibition induced earlier fibrinolysis. Secondly, I looked at the impact of EVs on coagulation by performing thrombin generation assays on plasma with EVs and without EVs (removed by ultracentrifugation), from patients with cirrhosis (all stages of severity). I found that removal of EVs from the plasma of cirrhosis patients had little impact on thrombin generation, whereas the impact was strong with plasma from healthy controls, suggesting that their role was less in coagulation in cirrhosis. Thirdly, in order to improve the prediction of post-procedural bleeding, I (i) studied the value of a comprehensive hemostasis work-up in 302 patients with cirrhosis and found that it did not improve bleeding prediction; (ii) surveyed 52 international experts on the bleeding risk associated with invasive procedures. The results enabled us to establish a consensus for 52 invasive procedures, 17 being classified as high risk of bleeding and 35 as low risk, and also to define thresholds for haemostasis tests (platelets, INR, aPTT, fibrinogen) enabling an invasive procedure to be carried out safely. In conclusion, my results show that, compared with healthy individuals, the hemostasis of patients with cirrhosis is characterized by (a) an increase in the circulating concentration of PN-1; (b) a role for PN-1 in fibrinolysis, since it inhibits excessive fibrinolysis; (c) a loss of the role of VEs in thrombin generation. From a practical point of view, neither global hemostasis tests nor circulating PN-1 concentration are predictive of post-LB bleeding. The expert consensus I have obtained allows us to classify invasive procedures to refine future studies and guide clinical decision-making

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Volpato, Julieta. "Efeitos da contenção física e química sobre as variáveis hematológicas e hemostáticas em gatos." Universidade do Estado de Santa Catarina, 2013. http://tede.udesc.br/handle/handle/896.

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Made available in DSpace on 2016-12-08T16:24:16Z (GMT). No. of bitstreams: 1 PGCA13MA119.pdf: 243424 bytes, checksum: 0b630548fe7f6b8f2081e1a779e8edd2 (MD5) Previous issue date: 2013-02-27 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior The blood sampling should not be influenced by factors that interfere in the results, but this is not always possible, especially in cats. The use of sedation protocols can assist in obtaining samples, but it is not known whether there are changes in haematological values and hemostasis. The aim of this study was to evaluate the parameters of the CBC, primary and secondary hemostasis of domestic cats under physical restraint and under different protocols of sedation. 50 cats were used from private owners, aged between one and seven years and with 3.32 Kg weight. The animals were randomly divided into two groups according to the association of drugs used: DB Group (25) dexmedetomidine (5 μg/kg) and butorphanol (0.3 mg/kg); DBC Group (25) dexmedetomidine (5 μg/kg), butorphanol (0.3 mg/kg) and ketamine (3 mg/kg), and all applications made by intramuscular injection. Blood samples were collected by jugular vein puncture in two moments, animals under physical restraint, and after applying one of the protocols of sedation. Scales were used to assess acute stress (zero to three) and evaluation of sedation (one to four). The parameters evaluated in two moments were the red cell count, hemoglobin, hematocrit, dosage globular volume (MCV), mean corpuscular hemoglobin concentration (CHGM), measurement of total plasma protein, platelet count, total and differential leukocyte count, clotting time, prothrombin time (PT) and activated partial thromboplastin time (Aptt), Thrombin time (TT). The bleeding time of the oral mucosa (TSMO) was carried out only after the use of sedation. The latent period was also measured. The results were evaluated by Sigma Plot computer program for Windows (2009), by applying the test of analysis of variance (ANOVA), and the observed differences were analyzed by Tukey test (p < 0.05). The values found for erythrocytes, hemoglobin, hematocrit, MCV, CHGM, platelets and leukocytes showed no statistical difference between the physical restraint and after the use of the sedation protocol or between sedation protocols. The coagulation time values showed no difference between moments and groups. The oral mucosal bleeding time showed no difference between the groups. Already the TP, APTT and TT values were different between groups, without difference between times. The stress evaluation showed that there was a predominance of animals with no stress or discreet stress during physical restraint. Sedation evaluation showed that the protocol used in DBC was more effective in relation to the DB group. As there were no clinically relevant changes in the values obtained under physical restraint and after the use of protocols, it is suggested that the use of these protocols of sedation does not interfere in the values of primary and secondary hemostasis and blood in healthy cats A colheita de amostras de sangue não deve ter influência de fatores que interfiram nos resultados, porém essa situação nem sempre é possível, sobretudo nos felídeos. O uso de protocolos de sedação pode auxiliar na obtenção de amostras, porém não se sabe se há alteração nos valores hematológicos e de hemostasia. O objetivo deste trabalho foi avaliar os parâmetros do hemograma, hemostasia primária e secundária de felinos domésticos sob contenção física e sob diferentes protocolos de sedação. Foram utilizados 50 gatos provenientes de proprietários particulares, com idade entre um e sete anos e com peso de 3,32 Kg. Os animais foram divididos aleatoriamente em dois grupos de acordo com a associação de drogas utilizadas: Grupo DB (25 animais) dexmedetomidina (5μg/kg) e butorfanol (0,3 mg/kg); Grupo DBC (25 animais) dexmedetomidina (5μg/kg), butorfanol (0,3 mg/kg) e cetamina (3mg/kg), sendo todas as aplicações realizadas pela via intramuscular. As amostras de sangue foram colhidas por punção da veia jugular em dois momentos, animais sob contenção física, e após a aplicação de um dos protocolos de sedação. Foram utilizadas escalas para avaliação do estresse agudo (zero a três) e para avaliação da sedação (um a quatro). Os parâmetros avaliados nos dois momentos foram contagem de eritrócitos, dosagem de hemoglobina, hematócrito, volume globular médio (VGM), concentração de hemoglobina globular média (CHGM), mensuração da proteína plasmática total, contagem de plaquetas, contagem total e diferencial de leucócitos, além do tempo de coagulação, tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPa) e tempo de trombina (TT). O tempo de sangramento da mucosa oral (TSMO) foi realizado somente após o uso de sedação. O período de latência também foi mensurado. Os resultados foram avaliados por programa computacional Sigma Plot for Windows (2009), aplicando-se o teste de análise de variância (ANOVA), sendo que as diferenças observadas foram analisadas pelo teste de Tukey (p<0,05). Os valores encontrados para eritrócitos, hemoglobina, hematócrito, VGM, CHGM, plaquetas e leucócitos, não apresentaram diferença estatística entre o momento contenção física e após o uso do protocolo de sedação, ou entre os protocolos de sedação. Os valores de tempo de coagulação não demonstraram diferença entre momentos e grupos. O tempo de sangramento da mucosa oral não apresentou diferença entre os grupos. Já o TP, TTPa e TT se mostraram diferentes entre grupos, sem diferenças entre momentos. A avaliação do estresse demonstrou que houve predomínio de animais com ausência de estresse ou estresse discreto durante a contenção física. A avaliação da sedação demonstrou que o protocolo utilizado no grupo DBC foi mais efetivo em relação ao grupo DB. Como não foram observadas alterações relevantes clinicamente nos valores obtidos sob contenção física e após a utilização dos protocolos, sugere-se que a utilização desses protocolos de sedação não interfere nos valores de hemograma e hemostasia primária e secundária em gatos saudáveis

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Dalmolin, Magnus Larruscaim. "Avaliação da hemostasia em cães: fator de Von Willebrand e tempo de protrombina e tromboplastina parcial ativada." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/115192.

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A doença de von Willebrand (DvW) é um defeito qualitativo/quantitativo do fator de von Willebrand (FvW), uma glicoproteína que desempenha um papel essencial na adesão e agregação plaquetária. Cães acometidos por esta diátese hemorrágica hereditária podem ser assintomáticos, ou apresentar sinais clínicos de um problema hemostático primário, especialmente hemorragias em superfícies mucosas. O diagnóstico da DvW baseia-se na quantificação do FvW plasmático, este sendo atualmente realizado por ELISA – antígeno FvW (Ag:FvW). O presente trabalho desenvolveu um ensaio para quantificação do Ag:FvW em amostras caninas e aplicou o teste em uma população de cães. Também determinou intervalos de referência para o ensaio e para tempos de coagulação. O ensaio apresentou R² médio de 0,9810, com coeficientes de variação intra-teste de 1,83 a 4,54% e entre-teste de 9,02 a 17,75%. Valores de referência para Ag:FvW, Tempo de Protrombina e Tempo de Tromboplastina Parcial Ativada obtidos foram de 24,87 a 224,5%, 6,0 a 9,3 segundos e 15,2 a 24,5 segundos, respectivamente. Completando, foi feita uma revisão da literatura sobre a doença em cães. Em conclusão, a determinação do Ag:FvW é um teste essencial para pacientes com histórico de diátese hemorrágica sem coagulopatia e/ou trombocitopenia e pode ser conclusivo para o diagnóstico de DvW. Obter valores de referência para a população local e padronizar os reagentes e instrumentos utilizados são extremamente importantes para um diagnóstico acurado dos distúrbios de hemostasia. Finalmente, um caso clínico de um cão com DvW também foi descrito. The von Willebrand disease (vWD) is a von Willebrand factor (vWF) quantitative/qualitative defect. This glycoprotein plays a crucial role on platelet adhesion and aggregation. Dogs affected by the hemorrhagic diathesis may be asymptomatics, or show clinical signs of a primary hemostatic disturbance, such as bleeding from mucosal surfaces. The diagnosis is based on vWF quantification by ELISA techniques – vWF antigen (vWF:Ag). The current study developed an assay for vWF:Ag quantification on canine samples, and the test was conducted on a dog population. Also, reference intervals were determined for this assay and for clotting times. The assay achieved a mean R² of 0.9810, with coefficient of variation for intra-assay of 1.83 to 4.54% and for inter-assay of 9.02 to 17.75%. The vWF:Ag assay, Prothrombin Time and activated Partial Thromboplastin Time reference intervals were 24.87 to 224.5%, 6.0 to 9.3 seconds and 15.2 to 24.5 seconds, respectively. In addition, a literature review about the disease in dogs was done. In conclusion, vWF:Ag determination is an essential assay for patients with hemorrhagic diathesis history without coagulopathy and/or thrombocytopenia, and might be conclusive for the disease diagnosis. Reference values for local population and standard protocols are extremely important for an accurate diagnosis of disorders of hemostasis. Finally, a case report of a dog with vWD was also described.

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Oliveira, Jéssica Rodrigues de. "Perfis hemostático e hematológico de cadelas acometidas por carcinoma mamário /." Jaboticabal, 2016. http://hdl.handle.net/11449/141990.

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Orientador: Márcia Ferreira da Rosa Sobreira Coorientador: Annelise Carla Camplesi Banca: Fábio Nelson Gava Banca: Sabryna Gouveia Calazans Resumo: Tumores mamários são frequentes em cadelas e apresenta comportamento biológico semelhante aos que ocorrem nas mulheres, tornando a cadela um excelente modelo de estudo comparativo. Os distúrbios hemostáticos são achados comuns em pacientes humanos com câncer, e os mecanismos que conduzem a ativação da coagulação no câncer envolvem o fator tissular, o fator procoagulante do câncer e as citocinas inflamatórias. E já está bem estabelecido que os componentes da hemostasia, como as plaquetas, proteínas da coagulação e da fibrinólise apresentam um papel importante no crescimento e na progressão do tumor. Assim, o objetivo deste estudo foi realizar a caracterização clínica, hematológica e histopatológica de cadelas acometidas por carcinoma mamário, bem como avaliar a integridade do sistema hemostático, através da mensuração do fibrinogênio plasmático, da contagem total de plaquetas, dos tempos de tromboplastina parcial ativada e de protrombina. Para tanto, foram utilizadas 62 cadelas. Sendo 32 acometidas por carcinoma mamário e 30 cadelas clinicamente e laboratorialmente saudáveis como grupo controle. Foram formados quatro subgrupos de acordo com o tipo e o grau histopatológico, estadiamento clínico e tamanho do tumor. Todas as cadelas acometidas por lesões mamárias foram submetidas ao exame físico das glândulas mamárias, exames de hemograma, testes de coagulação e ao exame de histopatológico. E os proprietários submetidos à anamnese por meio de questionário. A apresentação clínica ... (Resumo completo, clicar acesso eletrônico abaixo) Abstract: Mammary tumors are frequently found in female dogs. These tumors have shown a biological behavior similar to breast cancer in woman. This makes female dogs an excellent comparative study model. Coagulation disorders are common in human patients with cancer. Hemostasis is activated by inflammatory cytokines, tissue and procoagulant factors. It is well established that coagulation components as platelets and coagulation and fibrinolytic proteins have an important function in the growth an progression of tumors. Thus, the aim of this paper was to characterize clinical, hematological and histopathology female dogs with mammary carcinoma and evaluate the integrity of the hemostatic system by measuring the plasma fibrinogen, the total platelet count, and the activated partial thromboplastin and prothrombin time in female dogs. Sixty-two female dogs were used in this study. Thirty-two had mammary carcinoma and thirty were laboratorial and clinically healthy to be used as the control group. Four groups were formed according to histological type and grade, clinical stage and tumor size. The 32 female dogs with carcinoma were submitted to physical mammary gland, blood count, histopathological examinations and coagulation tests and their owners were submitted to a questionnaire. The clinical characteristics of the diseased dogs were older age, pure breed, not spayed with multiple stage one nodules. Grade I and II mixed carcinomas were the most frequent. In this study, significant diffe... (Complete abstract click electronic access below) Mestre

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Albert, Johanna. "Effects of nitric oxide on hemostasis with special attention to platelet function /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3783-4/.

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Sundström, Johanna. "Nanoparticle size-dependent activation of the hemostasis and the innate immune system." Thesis, Uppsala universitet, Institutionen för immunologi, genetik och patologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-298888.

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Nanoparticles are small particles with a size range of 10-1000 nm. They exist all around us, in make-up, dust and even food. They can enter our bloodstream through different pathways such as inhalation and cause thrombosis and multiple organ failure. They can be modified to act as drug deliverers and can treat even hard to reach places because of their small size. Studies have shown that the activation of the coagulation system and complement system is dependent on the size of the nanoparticle. This study’s main focus was to determine if there was a difference in the degree of activation on hemostasis and innate immunity by using four different nanoparticle sizes. The Chandler loop model makes it possible for blood to incubate with the nanoparticles and still be circulating in 37oC similar to the situation in the body. ELISA was thereafter performed on the plasma to determine the concentration of thrombin- antithrombin complex (TAT), C3a and Terminal Complement Complex (TCC). The most activating particles size on the complements system was 260 nm and for the coagulation system it was the 75 nm. FXII assay was performed and the results collaborated with the findings from the ELISA that the smallest particle sizes are most activating on the coagulation system. Taken together, smaller nanoparticle sizes are activating the coagulation system while the bigger nanoparticle sizes are more activating on the complement system. To confirm these results additional research should be performed to statistically confirm the importance of these findings.

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Souza, Evandro de Oliveira. "Avaliação funcional das plaquetas em pacientes com cirrose e sua relação com o risco de sangramento após ligadura elástica de varizes esofagianas." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5168/tde-16112017-081301/.

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Introdução: O sangramento por queda de escara é uma complicação potencialmente letal da ligadura elástica (LE) de varizes de esôfago. Os fatores relacionados a esse evento são pouco explorados na literatura, porém a coagulopatia, principalmente a plaquetopenia, do paciente com cirrose poderia estar implicada. O número e a função plaquetária têm particular relevância na manutenção da hemostasia, uma vez que a geração de trombina depende fortemente desses parâmetros. Entretanto, dados demonstram a preservação da função plaquetária como consequência de mecanismos compensatórios representados, principalmente, pelo aumento dos níveis do fator de von Willebrand (FVW) e diminuição de ADAMTS13. Deste modo, os pontos de corte para contagem plaquetária utilizados na prática clínica não refletiriam o risco de sangramento após procedimentos. Objetivos: O objetivo desse estudo foi descrever a função plaquetária em pacientes com cirrose e a sua influência no sangramento após LE de varizes de esôfago. Pacientes e Métodos: 1) Casuística. Foram incluídos pacientes com diagnóstico de cirrose, de diferentes etiologias, encaminhados para realização de LE como profilaxia primária ou secundária de sangramento por varizes de esôfago. Os critérios de inclusão foram: a) idade acima de 18 anos; b) pacientes com cirrose e varizes de esôfago com indicação de ligadura elástica eletiva e c) concordância em participar do estudo. Os critérios de exclusão foram: a) doenças pulmonares e cardíacas graves; b) carcinoma hepatocelular; c) insuficiência renal com uremia ou dialítica; d) uso de qualquer droga que interfere na coagulação. 2) Métodos. Imediatamente antes da realização da endoscopia digestiva com LE, foi coletada amostra de sangue de cada paciente para a realização dos seguintes testes: contagem de plaquetas, testes relacionados à função plaquetária (adesão e agregação medida pela superfície coberta (SC) com valor de referência: > 7,5% e tamanho do agregado (AS) com valor de referência: > 25um² pela tecnologia Impact- R®), antigeno de FVW (referência: 40-157%), atividade de FVW (referência: 38- 176%), proteinase ADAMTS13 (referência: 40-130%), P-selectina por citometria (34,9±2,32%) e P-selectina solúvel (92-212ng/mL). Os pacientes foram estratificados de acordo com número de plaquetas. O grau de comprometimento da função hepática foi avaliado pelos estadiamentos de Child-Pugh e MELD. O desfecho primário do estudo foi a ocorrência do sangramento atribuído à queda da escara da LE. Resultados: Foram incluídos 111 pacientes, divididos em três grupos: A) plaquetas < 50x10³/mm³ (n = 38; 34,2%); B) plaquetas entre 50x10³/mm³ e 100x10³/mm³ (n = 47; 42,4%) e C) plaquetas > 100x10³/mm³ (n = 26; 23,4%). Os três grupos não diferiram significativamente em relação aos seguintes parâmetros: gênero, etiologia e grau de disfunção hepática. Na comparação entre os grupos, os parâmetros hemoglobina e bilirrubina foram significantemente maior no grupo B (p=0,04 e p=0,009, respectivamente). Nos testes relacionados à função plaquetária, encontramos no Impact-R®, SC de 7 ± 4% e AS de 52 ± 24?m2. Na avaliação do FVW o valor encontrado foi de 369 ± 157% para o antígeno e 336 ± 149% para atividade. ADAMTS13 apresentou resultado 73 ± 24%. Na comparação entre os grupos: o parâmetro Impact-R® SC foi no grupo A: 4,9 ± 3%, no grupo B: 7,7 ± 4,6% e 9,1 ± 3,6 no grupo C (p < 0,005). O AS foi de 49,9 ± 22,4% no grupo A, no grupo B foi 55,1 ± 26,6% e 51,3 ± 20 no grupo C (p=0,599). Os outros parâmetros específicos relacionados à função plaquetária não foram significantes: o antígeno do FVW com p=0,926, a atividade do FVW com p=0,870 e ADAMTS13 com p=0,080. O resultado da P-selectina por citometria de fluxo foi de 37,8 ± 23% e P-selectina solúvel foi 182,3 ± 86 ng/mL. A maioria dos pacientes (58,5%) realizaram LE como profilaxia primária. A presença de sinais vermelhos ocorreu em 74% e a gastropatia hipertensiva foi vista em 95% dos pacientes. Houve sangramento após LE em seis (5,4%) pacientes, sendo duas ocorrências no grupo A, uma no grupo B e três no grupo C (p=0,316). O valor médio do MELD foi 13 ± 3,6, sendo 12,6 ± 3,3 no grupo sem sangramento e 16 ± 5,9 no grupo sem sangramento (p=0,025). Quando comparados os pacientes sem e com sangramento não encontramos diferença estatisticamente significante em nenhum parâmetro de função plaquetária. Conclusões: Os resultados dos testes de adesão e agregação plaquetária: SC e AS; FVW e ADAMTS13 demonstraram compensação funcional a despeito da plaquetopenia e não se correlacionaram com o risco de sangramento após LE de varizes de esôfago. O MELD foi significantemente maior nos pacientes que sangraram Introduction: Bleeding caused by ulceration after band ligation of esophageal varices is a potentially fatal complication. Contributing factors to this event are little explored in the literature, although coagulopathy, principally thrombocytopenia, in patients with cirrhosis could be implicated. The number and function of platelets has particular relevance to the maintenance of hemostasis, since thrombin generation depends heavily on these parameters. However, data show that the preservation of platelet function is a consequence of compensatory mechanisms represented principally by an increase in von Willebrand factor (VWF) levels and a reduction in ADAMTS13. Because of this, the cutoff points for platelet count used in routine clinical practice do not reflect the risk of bleeding following invasive procedures. Objective: The aim of this study was to describe platelet function in patients with cirrhosis and its influence on the bleeding following band ligation of esophageal varices. Methodology: 1) Inclusion. Patients with cirrhosis of different etiologies, referred for band ligation as primary or secondary prophylaxis of bleeding from esophageal varices were included. Inclusion criteria were: a) age > 18 years; b) patients with cirrhosis and esophageal varices elegible for elective band ligation; c) agreement to participate in the study. The exclusion criteria were: severe pulmonary or cardiovascular disease; b) hepatocellular carcinoma; c) renal dysfunction with uremia or requiring dialysis; d) use of any medication that could interfere with coagulation. 2) Methods. Immediately prior to digestive endoscopy with band ligation, a blood sample was taken from each patient to carry out the following coagulation tests: platelet count, platelet function test (adhesion and aggregation measured as surface coverage (SC) with normal range: > 7.5% and aggregate size (AS) with normal range: > 25um² by Impact-R® technology), antigen of VWF (normal range: 40- 157%), activity of VWF (normal range: 38-176%), protease ADAMTS13 (normal range: 40-130%), P-Selectin by cytometry (34.9±2.32%) and soluble P-Selectin (92- 212ng/mL). The degree of hepatic function was staged according to Child-Pugh and MELD. The principal clinical event assessed by the study was the occurrence of post-banding bleeding. Results: 111 patients were included in the study, divided into three groups: A) platelet count < 50x10³/mm³ (n=38; 34.2%); B) platelet count between 50x10³/mm³ and 100x10³/mm³ (n=47; 42.4%); and C) platelet count > 100x10³/mm³ (n=26; 23.4%). The three groups did not differ significantly in relation to the following parameters: gender, cirrhosis etiology and degree of hepatic dysfunction. The comparison among groups showed that the parameters hemoglobin and bilirubin were significantly higher in group B (p=0.04 and p=0.009, respectively). With regards to platelet function, in Impact-R® the mean SC was 7 ± 4%; in group A was 4.9 ± 3%, in group B was 7.7 ± 4.6% and 9,1 ± 3,6 in group C (p < 0.005). The AS was 52 ± 24?m2; in group A was 49.9 ± 22.4%, in group B was 55.1 ± 26.6% and 51.3 ± 20 in group C (p=0.599). The mean VWF value was 369 ± 157% for antigen and 336 ± 149% for activity. ADAMTS13 activity values were 73 ± 24%. The comparison among groups showed that the other specific parameters for platelet function were not significant: VWF antigen with p=0.926, VWF activity with p=0.870 and ADAMTS13 with p=0.080. The result of P-Selectin by flow cytometry was 37.8 ± 23% and soluble P-Selectin was 182.3 ± 86ng/mL. The majority of patients (58.5%) underwent band ligation as primary prophylaxis. Red signs appeared in 74%, and hypertensive gastropathy was seen in 95% of patients. There was bleeding following band ligation in 6 (5.4%) of patients, with 2 occurring in group A, 1 in group B, and 3 in group C (p=0.316). The mean MELD score was 13 ± 3.6, with 12.6 ± 3.3 in the group without bleeding, and 16 ± 5.9 in the group with bleeding (p=0.025). When patients with bleeding were compared with those without, there was no statistically significant difference in any parameter for platelet function. Conclusions: The results of the platelet function test SC and AS; VWF and ADAMTS13 tests showed functional compensation for thrombocytopenia, and did not correlate with the risk of bleeding following band ligation of esophageal varices. The MELD score was significantly higher in patients who suffered bleeding

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Souza, Maria Claudia de Campos Mello Inglez de. "Desenvolvimento e avaliação de método substitutivo para a prática da hemostasia em cadáveres quimicamente preservados." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/10/10137/tde-07062013-102925/.

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O aprendizado e o ensino da cirurgia veterinária envolvem o desenvolvimento de habilidades que podem ser obtidas em laboratórios, por meio de vários modelos já disponíveis, incluindo o treinamento em cadáveres. Nestes, quando comparados aos procedimentos em animais vivos, duas limitações são notadas e frequentemente mencionadas, e referem-se às alterações de consistência dos tecidos e à ausência de sangramento durante o treinamento cirúrgico. Este trabalho foi focado na superação destas questões, por meio da realização da simulação de circulação sanguínea em cadáveres adequadamente preservados, permitindo aos usuários do sistema a possibilidade de treinamento cirúrgico em um modelo mais próximo do animal vivo, viabilizando também o aprendizado e a prática da hemostasia. Depois de desenvolvido o sistema, o mesmo foi utilizado por estudantes de Medicina Veterinária com distintos níveis de experiência, que avaliaram todo o método por meio de questionário, ressaltando também os pontos positivos e negativos observados. Concluiu-se que é possível realizar a simulação de sangramento em cadáveres quimicamente preservados, e que tal sistema foi bem aceito por quem o utilizou, sendo mais uma alternativa para melhor preparar estudantes para as experiências em animais vivos que necessitem de intervenções cirúrgicas. Veterinary surgery demands skills acquisition and refinement that can be obtained in laboratories using several available models, including training on cadavers. Those, when compared to live animal procedures, two limitations are noted and often mentioned, and are due to tissue consistency alterations and absence of bleeding during surgical training. This work was focused on overcoming these issues, by performing blood flow simulation in properly chemically preserved cadavers, giving users of this system the possibility of surgical training in a model closer to live animal, also enabling learning and practice of hemostasis. After developed the system, it was used by veterinary students with distinct experience levels, evaluating the whole method through a questionnaire, emphasizing positive and negative aspects. It was concluded that bleeding simulation in chemically preserved cadavers is possible, and that such a system was well accepted by those who used it, being an alternative to better prepare students for experiments on live animals that require surgical interventions.

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Vieira, Carolina Okamoto. "Mecanismo hemostático da serpente Crotalus durissus terrificus (Ophidia: Viperidae, Crotalinae)." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/41/41135/tde-26012015-141001/.

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A hemostasia previne a perda de sangue após uma lesão vascular e garante a fluidez sanguínea. Para isso há a participação de células carreadoras de fator tissular e também de plaquetas, além de fatores plasmáticos, cofatores, fosfolipídios e íons cálcio que resultam na liberação dos fibrinopeptídios do fibrinogênio e polimerização dos monômeros de fibrina, transformando-os em fibrina estável. Os polifosfatos também participam da ativação da via intrínseca da cascata de coagulação ativando o fator XII e a pré-calicreína plasmática. Os répteis possuem peculiaridades quanto ao mecanismo de coagulação, apresentando níveis altos de anticoagulantes circulantes e ausência ou deficiência de alguns fatores de coagulação. Pouco se sabe sobre a participação real dos trombócitos e polifosfatos no mecanismo hemostático de serpentes. Assim, o objetivo deste estudo foi investigar o mecanismo hemostático da serpente de C.d. terrificus, avaliando também o papel dos trombócitos e dos polifosfatos. Os testes de coagulação apresentaram tempos prolongados, mas o nível de fibrinogênio (227, 47 ± 20,38 g/dL) foi semelhante ao humano. Foi constatada a presença de FXII, que foi ativado pelos polifosfatos, reduzindo o tempo de coagulação em Rotem. Os trombócitos de C.d. terrificus (13,37 ± 1,22 x 109/L) são células nucleadas elipsoidais, que apresentam superfície lisa quando não estão ativados. Esses trombócitos agregaram com colágeno 5,84 ± 0,85 Ω) e cálcio ionóforo (24 ± 3,3 %). Porém, não ativaram com ADP, como previamente mostrado em outros répteis. A adesão trombocitária observada (1,25 ± 0,37 %) foi mais baixa do que em seres humanos (11%), lembrando que a adaptação do método usado não foi totalmente adequada às serpentes. Embora se saiba pouco sobre a importância das variações das características morfológicas das fibras de fibrina, que em C.d. terrificus diferem das de ratos, humanos e outras espécies descritas de mamíferos, o tipo dessa rede de fibrina pode estar influenciando no processo final da hemostasia, juntamente com a participação dos trombócitos. A eficácia do mecanismo hemostático em serpentes C.d. terrificus parece estar relacionada principalmente à ativação da coagulação pelo fator tissular. Assim, a fase de iniciação é tão eficiente quanto em mamíferos, diferindo mais na fase de propagação do coágulo, ou seja, na via intrínseca. A baixa concentração de alguns fatores de coagulação e níveis elevados de inibidores naturais, tais como a antitrombina, interfere nesse sistema mais lento e possivelmente diminui os riscos trombóticos Hemostasis prevents blood loss after vascular injury and provides the blood flow. Platelets and tissue factor bearing cell, plasma factors, cofactors, phospholipids and calcium ions participate in this process that results in the release of fibrinogen fibrinopeptides and polymerization of fibrin monomers, converting to stable fibrin. Polyphosphates also participate in the activation of the intrinsic pathway of the coagulation cascade by activating factor XII and plasma prekallikrein. The peculiarities of blood coagulation of reptiles are high levels of circulating anticoagulants and absence or low level of some coagulation factors. The role of thrombocytes and polyphosphates in the hemostatic mechanism of snakes is not well known. The objective of this study was to investigate the hemostatic mechanism of C.d. terrificus snake evaluating the role of thrombocytes and polyphosphates. Coagulation tests showed prolonged times, but the level of fibrinogen (227.47 ± 20.38 g/dL) was similar to human. It was also observed the presence of FXII activated by polyphosphates reducing the clotting time in Rotem. Thrombocytes of C.d. terrificus (13.37 ± 1.22 x 109/L) are ellipsoidal nucleated cells, which exhibit smooth surface when not activated. These thrombocytes were activated by collagen (5.84 ± 0.85 Ω) and calcium ionophore (24 ± 3.3%). However, they did not aggregate with ADP as previously shown in other reptiles. The thrombocytes adhesiveness observed (1.25 ± 0.37%) was lower than in humans (11%), probably, in part because the adaptation of the method used was not fully adequate to snakes. Although little is known about the importance of morphological characteristics of C.d. terrificus fibrin fibers, which differ from rat, human and other mammalian species described, possibly this type of fibrin network may influence the final stages of hemostasis, with thrombocytes participation. The efficacy of the hemostatic mechanism in C.d. terrificus snakes seems to be mainly related to the activation of coagulation by tissue factor. Thus, the initiation phase is as efficient as in mammals, differing in the propagation phase of coagulation or intrinsic pathway. The low concentration of some coagulation factors and high levels of natural inhibitors such as antithrombin may be interfering with that system, and also preventing thrombotic diseases

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Aguiar, Juliana. "Eletrocoagulação bipolar e monopolar na ovariosalpingohisterectomia videocirurgica híbrida utilizando dois portais em felinos hígidos." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2011. http://hdl.handle.net/10183/32624.

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Neste trabalho foi realizado um estudo comparativo entre duas técnicas de oclusão do Complexo Artério Venoso Ovariano (CAVO), por meio da eletrocoagulação monopolar e bipolar, na ovariosalpingohisterectomia (OSH) de felinos hígidos, realizada a partir da técnica com dois portais na linha média ventral. A OSH é um dos procedimentos laparoscópicos mais realizados na casuística da Medicina Veterinária. Diferentes técnicas tem sido realizadas para a execução deste procedimento, dentre as variações incluem-se o número e a disposição dos trocartes, sendo recente a execução da técnica com dois portais. Os objetivos da pesquisa foram descrever a técnica da OSH em felinos com dois portais, bem como comparar a eficácia da eletrocoagulação monopolar e bipolar na obliteração do CAVO. Foram utilizadas 16 gatas adultas, distribuídas aleatoriamente em dois grupos de oito animais. Os procedimentos videocirúrgicos foram realizados por meio da inserção dos portais na linha média ventral nas regiões umbilical e pré-púbica, com os felinos posicionados em decúbito dorsal. Além da verificação da viabilidade da técnica com o uso de apenas dois portais lineares, foram avaliados e comparados o tempo cirúrgico, a eficácia dos dois métodos de eletrocoagulação, a temperatura corpórea pós-operatória, o débito urinário, a formação de enfisema subcutâneo e volume de CO2. Não houve diferença estatística significativa entre o uso da eletrocoagulação mono e bipolar, utilizados na técnica referida acima, embora clinicamente dois animais tenham apresentado lesões cutâneas após o uso da eletrocoagulação monopolar. Conclui-se que os dois métodos de eletrocoagulação utilizados para oclusão dos vasos ovarianos, através da técnica vídeo laparoscópica com dois portais em felinos, são viáveis, rápidos e efetivos em gatas, porém, a energia bipolar mostrou-se um método mais seguro do que a energia monopolar, devido a complicações por queimaduras cutâneas no período pósoperatório. In this paper, a comparative study was made between two techniques of occlusion of the ovarian arterial-venous complex (OVAC) through monopolar and bipolar electrocoagulation in ovariosalpingohysterectomy (OSH) of healthy cats, carried out from the technique with two linear portals in the ventral midline. The OSH is one of the most commonly performed laparoscopic procedures in casuistry of Veterinary Medicine. Different techniques have been carried out to implement this procedure, among the variations of this technique include the number and arrangement of the trocars, considering recent the implementation of the technique with the use of two portals. The research aims were to describe the technique of ovariohysterectomy in cats with two portals, and the comparison of the effectiveness of monopolar and bipolar electrocoagulation in obliterating of OVAC. Sixteen adult cats were used, divided randomly into two groups of eight animals. The laparoscopic procedures were performed through the insertion of the portals in the ventral midline of abdomen in the umbilical and prepubic regions, with cats under dorsal recumbence position. Besides the verification of the viability of the laparoscopic hybrid technique, using only two linear portals, the surgical time, the effectiveness of the two methods of electrocoagulation, the postoperative body temperature, urine output, the formation of subcutaneous emphysema and CO2 volume were evaluated and compared. There was no statistical significant difference between the use of mono and bipolar electrocoagulation, used in the technique mentioned above, although two animals showed clinical skin lesions after the use of monopolar electrocoagulation. We conclude that the two electrocoagulation methods used for occlusion of the ovarian vessels, through video-laparoscopic with two portals technique in cats, are viable, fast and effective in female cats, however, the bipolar energy proved to be a safer method than the monopolar energy, due to complications from skin burns in the postoperative period.

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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.

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Obinwa, Pia. "Stabilitet och hållbarhet av reagens efter nedfrysning och frystorkning för användning vid analys av trombocytfunktion med flödescytometri." Thesis, Linköpings universitet, Institutionen för medicin och hälsa, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-130030.

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Introduction: Hemostasis is a complex system in the body that maintains blood flow and prevents bleeding. Patients with platelet disorders are at the risk of mucocutaneous bleedings and at Clinical chemistry in Linköping platelet function is measured with flow cytometry. The platelet response to various agonists is measured with fluorescently labeled platelet antibodies. The aim of this study was to evaluate the stability of the frozen reagents used for platelet function testing. Further the durability of platelet antibodies after freezing and freeze-drying was tested. Method: Platelet antibodies were prepared for freezing/freeze-drying in buffer and were analyzed at three different occasions using blood from 2 to 3 individuals with flow cytometry. Agonists and blood were added on the day of analysis. The reagent stability test was evaluated statistically using one-way ANOVA with Bonferronis post-hoc test. Results: The slight drop in percent positive platelets and median fluorescence intensity (MFI) seen over time in the reagent stability test was not statistically significant (p>0,05). All platelet antibodies could be used after freezing/freeze-drying. The results are showing a declining trend, especially for MFI values. Conclusion: The frozen reagents used for platelet function testing is stabile up to 36 months. The results from the freeze-drying/freezing indicate that all platelet antibodies keep some activity but that some are more sensitive than others. Some antibodies could not be evaluated due to concentration of agonist in the sample being too low to induce activation. Due to individual variations further studies with more participants and more agonists in their optimal concentrations are needed. Bakgrund: Hemostas är ett komplext system i kroppen som upprätthåller blodflödet och förhindrar blödning. Mukokutana blödningar kan uppstå hos patienter som har problem i den primära hemostasen vilket kan bero på trombocydefekter. På Klinisk kemi i Linköping mäts trombocytfunktion med flödescytometri. Trombocyterna aktiveras med olika agonister och svaret på stimuli mäts genom detektion av fluoroforkonjugerade antikroppar. Syftet med denna studie var att utvärdera långtidsstabiliteten av de frysta reagens som används för trombocytfunktionsutredningen, att testa om nya trombocytantikroppar klarar att frysas och att utvärdera reagensens hållbarhet för frystorkning. Metod: Antikroppar frystorkades/frystes i buffert och analyserades vid tre tillfällen med blod från 2 till 3 personer med flödescytometri. Agonist och blod tillsattes på analysdagen. Långtidsstabilitetstestet utvärderades statistiskt med one-way ANOVA med Bonferronis post-hoc test. Resultat: En svag nedgång över tid i procent positiva trombocyter och MFI i långtidsstabilitetstestet var inte statistiskt signifikant (p>0,05). Alla antikroppar gav signal efter frysning och frystorkning. Främst för MFI syns en nedåtgående trend över tid. Slutsats: Reagenset för trombocytfunktionsutredningen är stabilt upp till 36 månader. Resultat från frystorkningen tyder på att alla antikroppar klarar att frystorkas/frysas men vissa är känsligare än andra. Vissa antikroppar kunde inte utvärderas p.g.a. för låg agonistkoncentration för att inducera aktivering. Ytterligare försök måste göras med fler individer och fler agonister i optimal koncentration p.g.a. individuella skillnader i svar för agonister. Frystorkningsprocessen kan optimeras.

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Pripp, Ulla. "The effect of sex hormones on hemostasis and cardiovascular riskfactors in postmenopausal women /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-982-X/.

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Buzała, Mateusz. "Variability of secondary hemostasis in broiler chickens administered in ovo with selected prebiotics." Rozprawa doktorska, Uniwersytet Technologiczno-Przyrodniczy w Bydgoszczy, 2015. http://dlibra.utp.edu.pl/Content/842.

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Celem badań było określenie parametrów krzepnięcia krwi (stężenia całkowitego TF i TFPI oraz aPTT i stężenia fibrynogenu) u kurcząt brojlerów w zależności od ich wieku oraz ocena wpływu podania w wyniku iniekcji in ovo wybranych prebiotyków na zmienność mechanizmów układu hemostazy podczas odchowu kurcząt brojlerów

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Kauhanen, Petteri. "Vascular regulation of hemostasis and fibrinolysis : with special focus on vein graft disease." Helsinki : University of Helsinki, 2001. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/kauhanen/.

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Dore, Celina Maria Pinto Guerra. "Aspectos estruturais, farmacol?gicos e biol?gicos de fucanas da alga marrom sargassum vulgare." Universidade Federal do Rio Grande do Norte, 2012. http://repositorio.ufrn.br:8080/jspui/handle/123456789/12570.

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Made available in DSpace on 2014-12-17T14:03:35Z (GMT). No. of bitstreams: 1 CelinaMPGD_TESE.pdf: 1816885 bytes, checksum: 1e39ca48cae61af571d696fef8f71be4 (MD5) Previous issue date: 2012-10-15 Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico The present study examines the chemical composition and their effects on free radicals, inflammation, angiogenesis, coagulation, VEGF effects and cellular proliferation of a polysaccharides from alga Sargassum vulgare. The sulfated polysaccharide was extracted from brown seaweed by proteolysis with enzymes maxataze. The presence of proteins and sugars were observed in crude polysaccharides. Fractionation of this crude extract was made with growing concentration of acetone (0.3-1.5 v) and produced four groups of polysaccharides. Anionic polysaccharides from brown seaweed Sargassum vulgare, SV1and PSV1 were fractionated (SV1) and purified (PSV1), and displayed with high total sugars and sulfate content and very low level of protein. This fucan SV1 contains low levels of protein and high carbohydrate and sulfate content. This polysaccharides prolonged activated partial thromboplastin time (aPTT) at 50 μg (>240 s). SV1 was found to have no effect on prothrombin time (PT), corresponding to the extrinsic pathway of coagulation. SV1 exhibits high antithrombotic action in vivo, with a concentration ten times higher than heparin. Polysaccharides from S. vulgare promoted direct inhibition enzymatic activity of thrombin and stimulated enzymatic activity of FXa. SV1 showed optimal inhibitory activity of thrombin (50.2?0.28%) at a concentration of 25 μg/mL. Its antioxidant action on scavenging radicals by DPPH was (22%), indicating the polymer has no cytotoxic action (hemolytic) on ABO and Rh blood types in different erythrocyte groups and displays strong anti-inflammatory action on all concentrations tested in the carrageenan-induced paw edema model, demonstrated by reduced edema and cellular infiltration. Angiogenesis is a dynamic process of proliferation and differentiation. It requires endothelial proliferation, migration, and tube formation. In this context, endothelial cells are a preferred target for several studies and therapies. The antiangiogenic efficacy of polysaccharides was examined in vivo in the chick chorioallantoic membrane (CAM) model by using fertilized eggs. Decreases in the density of the capillaries were assessed and scored. The results showed that SV1 and PSV1 have an inhibitory effect on angiogenesis. These results were also confirmed by inhibition tubulogenesis in rabbit aorta endothelial cell (RAEC) in matrigel. These compounds were assessed in Apoptosis assay (Annexin V - FITC / PI) and cell viability by MTT assay of RAEC. These polysaccharides do not affect the viability and do not have apoptotic or necrotic action. RAEC cell when incubated with SV1 and PSV1showed inhibition of VEGF secretion, observed when compounds were incubated at 25, 50 and 100 μg/μL. The VEGF secretion with the RAEC cell line for 24 h, was more effective for PSV1 at 50 μg/μL(71.4%) than SV1 100 μg/μL (75.9%). SV1 and PSV1 had an antiproliferative action (47%) against tumor cell line HeLa. Our results indicate that these sulfated polysaccharides have antiangiogenic and antitumoral actions O presente estudo analisa a composi??o qu?mica e seus efeitos sobre os radicais livres, inflama??o, angiog?nese, coagula??o, VEGF e prolifera??o celular dos polissacar?deos de uma alga Sargassum vulgare. O polissac?rido sulfatado foi extra?do a partir de algas marrons por prote?lise com a enzima maxataze. A presen?a de prote?nas e a??cares foram observados no cru de polissacarideos. Fracionamento do o extrato bruto foi feito com concentra??es crescente de acetona (0,3-1,5 v), produzindo quatro grupos de polissacarideos. Estes compostos ani?nicos da alga S. vulgare, foram fracionados (SV1) e purificados (PSV1) exibindo com alta a??cares totais e sulfatecontent e n?vel muito baixo de prote?nas.A fucana SV1 cont?m baixos n?veis de prote?na e de hidratos de carbono e alto teor de sulfato. Este polissacar?deos prolongou o tempo de tromboplastina parcial activada (aPTT) a 50 ug (>240 s). n?o foi observado qualquer efeito de SV1 sobre o tempo de protrombina (PT), que corresponde a via extr?nseca da coagula??o. SV1 exibiu alta a??o antitromb?tica in vivo, com uma concentra??o 10 vezes maior do que a heparina. SV1 promoveu a actividade de inibi??o enzim?tica direta da trombina e estimulou a atividade enzim?tica do FXa. Mostrou tamb?m, atividade inibidora optima de trombina (50,2 ? 0,28%) a uma concentra??o de 25 ug / mL. A sua ac??o anti-oxidante de radicais scavenging por DPPH foi de (22%), indicando que o pol?mero n?o tem qualquer a??o citot?xica (hemol?tica) em tipos de sangue ABO e Rh, em diferentes grupos de eritr?citos e exibindo alta a??o anti-inflamat?ria em edema de pata de ratos Wistar em todas as concentra??es testadas induzida por carragenina. Tal processo foi demonstrado por edema e infiltra??o celular. A angiogenese ? um processo din?mico de prolifera??o e diferencia??o. Ele requer prolifera??o endotelial, migra??o, e a forma??o do tubo. Neste contexto, as c?lulas endoteliais s?o um alvo preferido para muitos estudos e terapias. A efic?cia antiangiogenico de polissacar?deos foi examinada in vivo na membrana corioalant?ica pinto (CAM) usando-se ovos fertilizados. Diminui??es na densidade dos capilares foram avaliados e pontuados. Os resultados mostraram que SV1 e PSV1 tem um efeito inibidor da angiogenese. Estes resultados foram tamb?m confirmados por tubulogenesis inibi??o na c?lula endotelial da aorta de coelho (RAEC) em matrigel. C?lulas RAEC quando foram incubadas com SV1and PSV1 demonstraram inibi??o da secre??o de VEGF, a 25, 50 e 100 ug/mL. A secre??o de VEGF com a linha de c?lulas RAEC durante 24 h, foi mais eficaz para PSV1 a 50 ug / mL (71,4%) do que SV1 100 ug / mL (75,9%). SV1 e PSV1 posuiram uma ac??o antiproliferativa (47%) contra as c?lulas tumorais tipo HeLa. Estes compostos foram avaliados tamb?m, no ensaio de apoptose (anexina V - FITC / PI) e a viabilidade celular pelo ensaio de MTT de RAEC. Estes polissacar?deos n?o afetaram a viabilidade e n?o tiveram a??o apopt?tica ou necr?tica. Nossos resultados indicam que estes polissacar?deos sulfatados t?m a??es antiangiog?nica e antitumoral e constituem um importante alvo biol?gico e farmacol?gico

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Rieger, Alexandre. "Variabilidade genética da hemostasia como fator de risco para as complicações micro e macrovasculares do diabetes mellitus tipo 2." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2009. http://hdl.handle.net/10183/28433.

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Introdução: O diabetes mellitus tipo 2 (DM2) representa cerca de 90% dos tipos de diabetes e vem atingindo de forma cada vez mais intensa a população adulta e atualmente também jovens e até crianças. Uma dieta hipercalórica, aliada ao sedentarismo tem sido junto com a predisposição genética os principais desencadeantes das complicações crônicas associadas com o DM2. Infelizmente, são essas complicações que levam ao grande aumento da morbidade e mortalidade que pode chegar até 80% nesta doença, sendo que as principais são as de natureza micro e macrovascular. Complicações microvasculares compreendem a retinopatia diabética (RD), a nefropatia diabética (ND) e a neuropatia periférica (NP), enquanto que as complicações macrovasculares compreendem a doença cardiovascular (DCV), a doença arterial periférica (DAP) e o acidente vascular cerebral (AVC). Pacientes com DM2 em sua fase inicial já podem apresentar um quadro protrombótico que só tende a piorar com a progressão da doença. Esse quadro protrombótico é resultante principalmente do processo inflamatório e da disfunção endotelial. Polimorfismos genéticos relacionados com as diferentes fases da hemostasia podem contribuir para o aumento ou diminuição no risco de formação de trombos arteriais e venosos que podem afetar a micro e macrovasculatura destes indivíduos. Objetivos: Investigar a influência de polimorfismos envolvidos com a hemostasia como fatores de risco para o desenvolvimento de complicações crônicas micro e macrovasculares em pacientes com DM2. Metodologia: Foi realizado um estudo de caso controle aninhado em uma coorte de pacientes DM2 não relacionados provenientes de um estudo multicêntrico no sul do Brasil. Os pacientes DM2 foram divididos em 2 grupos de estudo. Para o grupo com complicação macrovascular estudou-se 404 pacientes DM2. Casos para a complicação macrovascular foram definidos como tendo cardiopatia isquêmica (CI), acidente vascular cerebral isquêmico (AVCI) ou DAP enquanto que controles foram definidos como pacientes com pelo menos 5 anos de DM2 e sem a respectiva complicação. Para o estudo das complicações microvasculares 393 pacientes com DM2 foram estudados. Os casos foram definidos como tendo RD, ND ou neuropatia sensório distal (NSD). Controles para a complicação microvascular foram pacientes com pelo menos 10 anos de DM2 e sem a respectiva complicação. Os polimorfismos estudados foram testados em duplicata utilizando-se a PCR seguida de RFLP quando necessário. Foram investigados nove polimorfismos assim distribuídos: Na fase da coagulação foram estudados cinco polimorfismos (FGB rs1800790, F2 rs1799963, FV rs6025 F7 rs5742910 e F13A rs5985); dois (PLAT rs4646972 e PAI-1 rs1799768) na fase da fibrinólise e um (ITGB3 rs5918) na fase plaquetária. O polimorfismo da MTHFR rs1801133 envolvido com a hiperhomocisteínemia é considerado um fator de risco para DCV e por isso foi incluído. Para a análise estatística foi utilizado o teste do χ2 para a comparação das frequências genotípicas e alélicas. Os polimorfismos com diferença significativa foram testados na regressão de Poisson com variância robusta ajustado pelas variáveis de confusão. Para as complicações microvasculares também foi utilizado o teste do χ2 com análise de resíduo ajustado. Resultados: O polimorfismo do receptor plaquetário ITGB3 rs5918 apresentou associação com os desfechos AVCI e DAP. Para o desfecho AVCI o genótipo 176TC mostrou associação significativa [(PR = 2.04(1.11-3.73); P = 0.021], enquanto que para a DAP a associação foi com o genótipo 176CC [PR = 1.90(1.29-2.81); P = 0.001]. Em relação às complicações microvasculares o único polimorfismo que mostrou associação foi o PAI-1 rs1799768. Neste caso, o polimorfismo demonstrou ter uma associação inesperada para o alelo 4G como um fator de proteção quando comparamos pacientes com e sem ND [PR = 0.71(0.57-0.89); P = 0.003]. Porém, quando foi estratificado o grupo de pacientes com ND de acordo com a severidade, foi possível demonstrar usando a análise de resíduo ajustado do teste do χ2 que havia uma diminuição significativa na frequência do alelo 4G somente no estágio mais avançado da doença renal (P = 0.009; AR = -2.95) o que sugere o seu envolvimento com uma maior taxa de mortalidade na ND. Também foi possível mostrar que o alelo de risco 4G está significativamente associado com a cardiopatia isquêmica nos indivíduos com ND (P = 0.03; AR = 2.5). Conclusões: Os pacientes com DM2 portadores do alelo de risco 176C do polimorfismo ITGB3 rs5918 apresentam um risco significativamente aumentado de desenvolver AVCI e DAP, enquanto que os portadores do alelo de risco 4G do polimorfismo PAI-1 rs1799768 provavelmente apresentem maior risco de desenvolver ND. Além disso, os portadores do alelo 4G e que tem ND apresentaram um risco significativamente aumentado de desenvolverem CI. Introduction: Type 2 diabetes mellitus (T2DM) represents approximately 90% of the diabetes types, increasingly affecting the adult population and nowadays also occurring in young adults and children. Hypercaloric diets, sedentarism and genetic predisposition are the main triggering factors of chronic complications associated to T2DM. Unfortunately, these are the complications that lead to a considerable increase in morbidity and mortality, which may reach 80%, with the main complications being of micro- and macrovascular nature. The microvascular complications are diabetic retinopathy (DR), diabetic nephropathy (DN) and peripheral neuropathy (PN). The macrovascular complications include cardiovascular disease (CVD), peripheral arterial disease (PAD) and stroke. In the initial T2DM stage, patients may present a prothrombotic state that tends to worsen as the disease evolves. This prothrombotic state results mainly from the inflammatory process and from the endothelial dysfunction. Genetic polymorphisms related to the different stages of hemostasis may play a role in the increase or decrease of the risk of arterial and venous thrombus, which may affect the micro- and the macrovasculature of these individuals. Objectives: To investigate the influence of the polymorphisms related to hemostasis as risk factors for the development of micro- and macrovascular complications in T2DM patients. Methods: A nested case-control study was conducted with a cohort of unrelated T2DM patients from a multicenter study made in southern Brazil. T2DM patients were divided in two groups. The macrovascular complication group included 404 T2DM patients. Macrovascular complications were defined according to the presence of the following criteria: ischemic heart disease (IHD), ischemic stroke (IS) or PAD. The control group was formed by patients who had had T2DM for at least five years but without the respective complications. The microvascular complication group included 393 T2DM patients. Microvascular complications were defined based on the presence of the following criteria: DR, DN, or distal sensory neuropathy (DSN). The controls used in the investigation of the microvascular complications were patients who had T2DM for at least 10 years, without the respective complications. The polymorphisms investigated were analyzed by PCR with RFLP, when necessary. In total, nine polymorphisms were studied. Five polymorphisms (FGB rs1800790, F2 rs1799963, FV rs6025, F7 rs5742910 and F13A1 rs5985) were investigated for the coagulation stage, two (PLAT rs4646972 and PAI-1 rs1799768) for the fibrinolysis stage, and one (ITGB3 rs5918) for the platelet stage. The polymorphism MTHFR rs1801133, associated to hyperhomocysteinemia, which is considered a risk factor for IHD, was also investigated. The statistical analysis used the χ² test to compare genotypic and allelic frequencies. The polymorphisms presenting significant differences were tested using the Poisson regression with robust variance adjusted for the confounding variables. The χ² test with the analysis of adjusted residues was also used for microvascular complications. Results: The polymorphism of the platelet receptor ITGB3 rs5918 was associated with the outcomes IS and PAD. Considering IS, the genotype 176TC exhibited significant association [(PR = 2.04(1.11-3.73); P = 0.021], while considering PAD the association was with genotype 176CC [PR = 1.90(1.29-2.81); P = 0.001]. Regarding the microvascular complications, the only polymorphism that presented association was PAI-1 rs1799768. In this case, the polymorphism demonstrated an unexpected association with allele 4G as a protection factor when patients with and without DN [PR = 0.71(0.57-0.89); P = 0.003]. However, when the group of patients with DN was stratified in terms of severity, it was possible to demonstrate a significant decrease in 4G allele frequency only n the more advanced stage of the renal disease, using the adjusted residue of the χ2 test (P = 0.009; AR = -2.95), which suggests its involvement with a higher mortality rate in DN. It was also possible to show that the risk allele 4G is significantly associated with ischemic cardiopathy in individuals with DN (P = 0.03; AR = 2.5). Conclusions: The T2DM patients carriers of the risk allele 176C of the polymorphism ITGB3 rs5918 present a significantly increased risk of developing IS and PAD, while carriers of the risk allele 4G of the polymorphism PAI-1 rs1799768 probably present higher risk of developing DN. Apart from this, this group of subjects also presented a significant risk of developing IHD.

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Khandekar, Gauri. "Origin and Role of Factor Viia." Thesis, University of North Texas, 2013. https://digital.library.unt.edu/ark:/67531/metadc407814/.

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Factor VII, the initiator of the extrinsic coagulation cascade, circulates in human plasma mainly in its zymogen form, Factor VII and in small amounts in its activated form, Factor VIIa. However, the mechanism of initial generation of Factor VIIa is not known despite intensive research using currently available model systems. Earlier findings suggested serine proteases Factor VII activating protease, and hepsin play a role in activating Factor VII, however, it has remained controversial. In this work I estimated the levels of Factor VIIa and Factor VII for the first time in adult zebrafish plasma and also reevaluated the role of the above two serine proteases in activating Factor VII in vivo using zebrafish as a model system. Knockdown of factor VII activating protease did not reduce Factor VIIa levels while hepsin knockdown reduced Factor VIIa levels. After identifying role of hepsin in Factor VII activation in zebrafish, I wanted to identify novel serine proteases playing a role in Factor VII activation. However, a large scale knockdown of all serine proteases in zebrafish genome using available knockdown techniques is prohibitively expensive. Hence, I developed an inexpensive gene knockdown method which was validated with IIb gene knockdown, and knockdown all serine proteases in zebrafish genome. On performing the genetic screen I identified 2 novel genes, hepatocytes growth factor like and prostasin involved in Factor VII activation.

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Poliachik, Sandra Louise. "An investigaton of the mechanisms of high intensity focused ultrasound induced platelet activity /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/8011.

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Dudka, I. V. "Condition of hemostasis system in patients with chronic obstructive pulmonary disease and chronic pancreatitis." Thesis, БДМУ, 2021. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/18585.

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Baracat, Felipe Iankelevich. "Hemostasia endoscópica para o sangramento da úlcera péptica: revisão sistemática e meta-análises." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5168/tde-28072017-092110/.

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Contexto: A hemorragia digestiva alta (HDA) resulta em 200 a 300 mil internações por ano nos Estados Unidos, com uma mortalidade de 2,5% a 10%. A úlcera péptica representa a causa mais comum de HDA, correspondendo por um terço a metade de todos os casos. Apesar das melhorias na compreensão de sua etiologia, a incidência de sangramento da úlcera péptica, sua complicação mais comum, não se alterou nas últimas décadas. A terapia endoscópica para HDA pode reduzir drasticamente o risco de ressangramento ou sangramento contínuo, a necessidade de cirurgia de urgência, o número de unidades de concentrado de hemácias para transfusão, o tempo de internação hospitalar e a mortalidade. O tratamento endoscópico da úlcera hemorrágica já percorreu um longo caminho desde injeções de adrenalina e outras soluções, o uso da termocoagulação, até a aplicação de dispositivos mecânicos, como o clipe metálico e a ligadura elástica. Objetivo: Permanece por esclarecer qual é a modalidade endoscópica (ou combinação de modalidades) que apresenta os melhores resultados no tratamento da hemorragia digestiva decorrente da úlcera péptica. Portanto, o objetivo desta revisão sistemática é comparar as diferentes modalidades de tratamento endoscópico da HDA decorrente da úlcera péptica, utilizando ensaios clínicos randomizados. Fontes de dados: Os estudos foram identificados através de pesquisa em bases de dados eletrônicas e listas de referência de artigos. As bases de dados pesquisadas foram Medline, Embase, Cochrane, LILACS, Dare e CINAHL. Critérios de elegibilidade de estudo, participantes e intervenções: Os estudos selecionados foram os ensaios clínicos randomizados comparando as diferentes modalidades endoscópicas para o tratamento de pacientes com hemorragia digestiva alta causada por úlcera péptica. Os estudos incluídos avaliaram técnicas endoscópicas contemporâneas de hemostasia: terapia de injeção endoscópica (todas as soluções, simples ou múltiplas), termocoagulação (heater probe, coagulação com plasma de argônio, coagulação com micro-ondas, eletrocoagulação monopolar, bipolar e multipolar), aplicação de clipes metálicos e tratamento combinado. Os desfechos avaliados foram as taxas de hemostasia inicial, ressangramento, cirurgia de urgência e de mortalidade. Avaliação de vieses: Ao nível de cada estudo, os revisores determinaram a adequação da randomização e da alocação; cegamento de pacientes, profissionais de saúde, coletores de dados e avaliadores de resultados; bem como o relato e a extensão das perdas de seguimento. Também foi avaliado se as técnicas de hemostasia endoscópica foram devidamente descritas e, se os desfechos foram adequadamente definidos em cada estudo. A análise de sensibilidade foi realizada quando a heterogeneidade (I2) foi superior a 50% e uma nova meta-análise foi calculada excluindo o(s) estudo(s) discrepante(s). Uma análise adicional foi realizada em cada comparação, incluindo apenas os ensaios de qualidade metodológica mais elevada. Resultados principais: Um total de 28 ensaios clínicos randomizados (envolvendo 2988 pacientes) foram avaliados nesta revisão, eles foram divididos em sete grupos de comparação de acordo com as modalidades estudadas em cada estudo. A terapia de injeção endoscópica como modalidade única foi inferior à sua combinação com o clipe metálico e com a termocoagulação na avaliação de taxa de ressangramento (diferença dos riscos [DR] = -0,10, intervalo de confiança de 95% [IC95%] = -0,18 a -0,03 e [DR] = -0,08, [IC95%] = -0,14 a -0,02, respectivamente) e na necessidade de cirurgia de urgência ([DR] = -0,11, [IC95%] = -0,18 a -0,04 e [DR] = -0,06, [IC95%] = -0,12 para -0,00, respectivamente). A aplicação de clipes metálicos foi superior à terapia de injeção endoscópica na avaliação da taxa de ressangramento ([DR] = -0,13, [IC95%] = -0,19 para -0,08), e os resultados da comparação entre a aplicação de clipes metálicos como monoterapia e a sua combinação com a terapia de injeção endoscópica não apresentaram diferenças estatísticas. A comparação entre o clipe metálico e a termocoagulação encontrou uma considerável heterogeneidade entre as intervenções utilizadas em cada estudo e nos resultados encontrados das meta-análises. A comparação da termocoagulação com a terapia de injeção endoscópica não evidenciou qualquer diferença estatística entre as modalidades, e a combinação delas é superior à técnica de termocoagulação sozinha ao avaliar a taxa de ressangramento ([DR] = -0,11, [IC95%] = -0,21 para - 0,02). Conclusões: A terapia de injeção endoscópica não deve ser empregada isoladamente. A aplicação de clipes metálicos é superior à terapia de injeção endoscópica, e a associação da injeção endoscópica não melhora a eficácia hemostática do uso isolado do clipe metálico. Como modalidade única, uma técnica de termocoagulação tem uma eficácia hemostática semelhante à terapia de injeção endoscópica, e estas modalidades combinadas parecem ser superiores à técnica de termocoagulação sozinha. Portanto, recomendamos a aplicação de clipes metálicos ou o uso combinado de uma terapia de injeção endoscópica com um método de termocoagulação para o tratamento de pacientes com hemorragia digestiva alta por úlcera péptica Background: Upper Gastrointestinal bleeding (UGIB) results in 200,00 to 300,000 hospital admissions annually in the United States, with a mortality of 2,5% to 10%. Peptic ulcer disease represents the most common cause of UGIB, accounting for a third to a half of all episodes. Despite improvements in the understanding of its etiology, the incidence of bleeding from peptic ulcer disease, the most common complication, has not changed. Endoscopic therapy for active UGIB can dramatically reduce the risk of rebleeding or continued bleeding, the need for surgery, the number of units of packed erythrocytes required for transfusion, the length of hospital stay and mortality. Endoscopic treatment for ulcer bleeding has come a long way from injections of epinephrine and other solutions, the use of thermocoagulation, to the application of mechanical devices such as hemoclips and banding ligator. Objective: It remains unclear which is the endoscopic modality (or combination of modalities) that presents the best results in the treatment of peptic ulcer bleeding. Therefore, the objective of this systematic review is to compare the different modalities of endoscopic hemostatic therapy, using randomized clinical trials. Data sources: Studies were identified by searching electronic databases and scanning reference lists of articles. The searched databases were Medline, Embase, Cochrane, LILACS, DARE and CINAHL. Study eligibility criteria, participants and interventions: The studies selected were the randomized clinical trials comparing different endoscopic modalities for the treatment of patients presenting with acute upper gastrointestinal bleeding caused by peptic ulcer disease. The included trials assessed contemporary endoscopic hemostatic techniques: endoscopic injection therapy (all injectates, single or multiple), thermal coagulation (heater probe, argon plasma and microwave coagulation, monopolar, bipolar and multipolar electrocoagulations), hemoclip placement and combination treatment. The outcomes measured were the rates of initial hemostasis, rebleeding, emergency surgery and overall mortality. Risk of bias assessment: At the study level, the reviewers determined the adequacy of randomization and concealment of allocation; blinding of patients, of health care providers, of data collectors, and of outcome assessors; and the correct report and extent of loss to follow-up. It was also evaluated whether the endoscopic hemostatic techniques were properly described and if the outcomes were appropriately defined in each study. A sensitivity analysis was held when the heterogeneity (I2) was over 50% and a new meta-analysis was calculated excluding the outlier(s). An additional analysis was made at each comparison, including only the higher methodological quality trials. Main results: A total of 28 trials, involving 2988 patients were evaluated in this review, they were divided into seven comparison groups according to the modalities studied in each trial. Injection Therapy as single modality was inferior to its combination with Hemoclip and with Thermal Coagulation Therapy when evaluating rebleeding rate (risk difference [RD] = -0.10, 95% confidence interval [95%CI] = -0.18 to -0.03 and [RD] = -0.08, [95%CI] = -0.14 to -0.02, respectively) and need for emergency surgery ([RD] = -0.11, [95%CI] = -0.18 to -0.04 and [RD] = -0.06, [95%CI] = -0.12 to -0.00, respectively). Hemoclip was superior to Injection Therapy in the evaluation of rebleeding rate ([RD] = -0.13, [95%CI] = -0.19 to -0.08), and the results of the comparison between Hemoclip alone versus its combination with Injection Therapy did not present any statistical differences. The comparison between Hemoclip and Thermal Coagulation encountered a considerable heterogeneity between the trials in the interventions used and in the results found. The comparison of Thermal Coagulation versus Injection Therapy did not evidence any statistical difference between the modalities, and the combination of these is superior to the Thermal Coagulation alone when evaluating rebleeding rate ([RD] = -0.11, [95%CI] = -0.21 to -0.02. Conclusions: Injection therapy should not be used as single modality. The application of Hemoclip is superior to injection therapy, and the combined application of an injectate does not improve the hemostatic efficacy of the use of Hemoclip alone. As single modality, a thermal coagulation technique has a similar hemostatic efficacy as injection therapy, and these combined modalities appear to be superior to thermal coagulation technique alone. Therefore, we recommend the application of Hemoclips or the combined use of an Injection Therapy with a Thermal Coagulation method for the treatment of patients presenting with acute peptic ulcer bleeding

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Lino, Ciro Novaes Rosa. "Caracterização da atividade biológica da serpina salivar AET-7393 de Aedes aegypti." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-18032014-181542/.

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Para conseguirem se alimentar com sucesso, os mosquitos hematófagos possuem componentes em sua saliva capazes de regular a hemostasia e modular a imunidade dos hospedeiros. Entretanto, a avaliação das atividades biológicas dessas moléculas no hospedeiro ainda carece de estudos mais aprofundados. No presente projeto, propomos caracterizar as atividades biológicas do produto do transcrito AET-7393, uma serpina presente nas glândulas salivares de fêmeas do mosquito Aedes aegypti. Nossos dados mostram que a serpina AET-7393 recombinante provoca um aumento no sangramento quando inoculada em camundongos, mas aparentemente esse efeito não está ligado à interferência com a cascata de coagulação. Mostramos ainda que a AET-7393 é capaz de inibir a proteinase 3 e aumentar a produção de IL-1b. Por fim, observamos a ausência de capacidade moduladora sobre a ativação de macrófagos ou sobre a inflamação, e que presença de anticorpos específicos contra a serpina no hospedeiro não interfere no ciclo de vida do mosquito. In order to successfully feed, hematophagous mosquitoes possess salivary components capable of regulating hemostasis and modulate the host immunity. However, the evaluation of the biological activities of the salivary molecules in the host still needs further investigation. In this study, we intend to characterize the biological activities of the AET-7393, a serpin that is present in the saliva of the females Aedes aegypti mosquitoes. Our data show that the recombinant AET-7393 serpin increases bleeding when inoculated in mice, but apparently this effect is not due to its interference on the coagulation cascade. In addition, AET-7393 is able to inhibit proteinase 3 and enhance the production of IL-1b. Finally, we observed the absence of modulatory effect on macrophage activation or inflammation, and that the presence of host anti-AET-7393 antibodies does not interfere in the life cycle of the mosquitoes.

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Jones, Tina. "Interventional cardiology: a portfolio of research pertaining to femoral sheath removal practices and patient education." Title page, table of contents and portfolio structure and overview only, 2003. http://web4.library.adelaide.edu.au/theses/09DNS/09dnsj798.pdf.

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"March 2003" Includes bibliographical references (leaves 61-68). Appendices: Publications arising from the research portfolio. 1. Conducting a systematic review -- 2. The effectiveness of mechanical compression devices in attaining hemostasis after removal of a femoral sheath following femoral artery cannulation for cardiac interventional procedures : a systematic review -- 3. Effectiveness of mechanical compression devices in attaining hemostasis after femoral sheath removal Contains three separate research projects, presented as separate reports, but all related to one area of interest - interventional cardiology. Seeks to identify effective femoral sheath removal practices after interventional cardiac procedures and determine patient's perceptions of the education prior to and after interventional procedures.

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Raghu, Harini. "Mechanisms Coupling Hemostatic Factors to Inflammatory Arthritis." University of Cincinnati / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406900762.

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Leme, Junior Paulo de Tarso de Oliveira. "MÚSCULO AUTÓGENO NA HEMOSTASIA TEMPORÁRIA DO PLEXO VENOSO VERTEBRAL VENTRAL DE COELHOS SUBMETIDOS Á HEMILAMINECTOMIA TORACOLOMBAR." Universidade Federal de Santa Maria, 2012. http://repositorio.ufsm.br/handle/1/10145.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico The objective of this experiment was to document the postoperative evolution of New Zealand rabbits that underwent a hemi laminectomy surgery (T13-L1) and received a graft of autogenous muscle as an hemostatic agent into the spinal canal. These animals were followed for a period of 14 and 28 days with daily neurological assessments and, at the end of their follow-up period, were euthanized in order to remove the graft site to be examined microscopically. The animals were divided into 6 groups such as the control group A and B, C and D treated with 25% decrease of the medullary canal and, E and F treated with 50% decrease of the medullary canal. All groups were evaluated neurologically every day until euthanasia. Groups A, C and E were euthanized at 14 days after the surgery and groups B, D and F at 28 days. The segments T11-L3 vertebral column of all the rabbits were collected and sent for histopathological examination. In order to evaluate the neurological postoperative effect, the animals were classified daily by the Tarlov scale and the results were compared by nonparametric Kruskal-Wallis test for each time (days). There was no statistical difference among the groups. Histopathological examination showed the presence of muscle grafted in the spinal canal and the spinal cord compression caused by the graft. A hemorragia é uma preocupação importante em pacientes submetidos a intervenção cirúrgica descompressiva da medula espinhal ou de estabilização na coluna vertebral. O objetivo desse experimento foi documentar a evolução pós-operatória de coelhos Nova Zelândia que sofreram hemilaminectomia (T13-L1) e receberam um segmento de músculo autógeno como agente hemostático dentro do canal vertebral. Os animais foram separados em seis grupos sendo os grupos A e B controle, C e D tratados com diminuição de 25% do canal medular e E e F tratados com diminuição de 50% do canal medular. Todos os coelhos tiveram avaliação neurológica diária até a eutanásia. Aqueles dos grupos A, C e E sofreram eutanásia aos 14 dias de pós-operatório e os demais (B, D e E) aos 28 dias. Os segmentos T11-L3 da coluna vertebral contendo a medula espinhal de todos os coelhos foram coletados e enviados para exame histopatológico. Para avaliação neurológica no pós-operatório, os animais foram classificados diariamente pela escala de Tarlov e os resultados foram comparados entre eles pelo teste não paramétrico de Kruskal-Wallis para cada tempo (dia). Não houve diferença estatística da avaliação neurológica entre os grupos estudados. O exame histopatológico demonstrou a presença do músculo transplantado no canal vertebral e a compressão da medula espinhal provocada pelo enxerto.

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Morrow, Gael Beverley. "Platelets harbour pro- and anti-fibrinolytic proteins on their activated membrane surface that regulate fibrinolysis of thrombi formed under flow." Thesis, University of Aberdeen, 2018. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=237022.

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Platelets play an essential role in haemostasis by adhering to the damaged vessel wall and forming a platelet plug to arrest bleeding. Although platelets are traditionally thought of as pro-coagulant, they possess the ability to harbour functional proteins that are key to fibrinolysis, the breakdown of the blood clot, on their surface. They are therefore substantially well equipped to regulate local fibrinolysis. This thesis aims to further define the role of platelets in fibrinolysis, in particular platelet-derived plasminogen activator inhibitor 1 (PAI-1) and plasminogen. PAI-1 is the principal physiological inhibitor of tissue-type plasminogen activator (tPA), and plasminogen is the zymogen for plasmin. In Chapter 3, we show that platelet-derived PAI-1 is released from platelet α-granules by an αIIbβ3 and fibrin dependent mechanism. We found that a significant portion of α-granular PAI1 is retained on the surface of highly activated PS-positive platelets, and activity analysis revealed the majority of PAI-1 on the platelet surface was in its active form. The functional role of platelet PAI-1 was investigated by analysis of tPA-mediated lysis of Chandler model thrombi. Our data revealed a striking dependence for platelet PAI-1 in stabilising platelet-rich thrombi against degradation. Chapter 4 characterises the expression of a novel transmembrane receptor, Plg-RKT, on the surface of human and mouse platelets. This revealed that plasminogen and Plg-RKT augment one another's binding to the platelet surface. Furthermore, analysis of plasminogen binding to the platelet surface revealed two distinct binding sites: 1) via Plg-RKT and 2) via a fibrin and αIIbβ3 dependent mechanism. Finally, Chapter 5 of this thesis discusses the optimisation of a system that monitors thrombus formation and fibrinolysis under flow. Use of this model will help to further elucidate the complex role that platelets play in controlling the balance between coagulation and fibrinolysis.

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Carter, Tiffany. "Hemostatic efficiency of amphiphilic peptide solution in Wistar Rat model." Thesis, Kansas State University, 2014. http://hdl.handle.net/2097/35239.

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Master of Science Department of Grain Science and Industry X. Susan Sun One of the leading causes of death following traumatic injury is exsanguination. The body addresses bleeding through the process of hemostasis which includes the formation of a fibrin mesh structure that holds a blood clot together. During traumatic injury, hemostasis may be unable to stop excess bleeding. Fibrin based hemostatic agents have been developed, however, these studies often use fibrin obtained from biological sources, which poses risk of infection. A novel amphiphilic peptide (h9e) has been studied to form three dimensional nanofibers networks. In this research, we studied the ability to form a synthetically produced, fibrin-mimic, hemostatic material from the h9e peptide sequence. The objective of this study was to determine the blood gelation strength of the h9e peptide necessary to arrest bleeding in the Wistar Rat model. Commercial mouse blood was used for blood gelation in vitro studies. Dynamic rheometer was used to determine the gelation kinetics at varied h9e peptide concentrations ranging from 1-5% wt. By directly mixing the h9e peptide with blood, we observed that the blood gelation strength right after mixing increased as the h9e peptide weight % concentration increased, from 67 to 1086 Pascals in the peptide concentration from 1 to 5%, respectively. After 24 hours, final gelation strength of all concentrations with commercial mouse blood was lower than the instantaneous strength but consistent throughout testing. Similar testing was conducted using commercial Wistar Rat blood with weight % concentrations of 1, 3, and 5% of h9e peptide. The gelation strength was 500, 1665, and 1914 Pascals, respectively. We also determined the gelation strength of Wistar Rat blood components, such as red blood cells, serum, and plasma with 1% h9e peptide. We observed the gelation response induced with individual blood components; however, the strength is weaker than whole blood. In vivo, we applied the cut-tail method by dipping the cut-tail of Wistar Rats into the h9e peptide solutions for 10 seconds and then took it out for blood lost collection. We observed that h9e peptide solution at 1, 3, and 5% weight concentrations can all generate hemostatic function. The h9e peptide solution at 5% weight concentration (1914 Pa) was able to outperform a commercial hemostatic material (Moore Medical CELOX* Hemostatic Granules), significantly reducing both bleeding time and blood lost: h9e peptide at 5% had a bleeding time of 94 sec and 0.75 mL blood lost, while the Celox hemostatic granules had a bleeding time of 225 sec and 1.5 mL blood lost. Transmission Electron Microscopy and Spinning Disk Confocal Microscope imaging indicated a blood component reinforced, web-like, h9e nanofiber structure similar to the structure formed by fibrin in a blood clot. This study showed that h9e peptide has the potential to be used to induce hemostasis.

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Dissertations / Theses on the topic 'Hemostasis'

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