Academic literature on the topic 'Fibrin Blood coagulation'
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Journal articles on the topic "Fibrin Blood coagulation"
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Mutch, Nicola J. "Regulation of Coagulation by Polyphosphate." Blood 134, Supplement_1 (November 13, 2019): SCI—18—SCI—18. http://dx.doi.org/10.1182/blood-2019-121062.
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Polyphosphate (polyP) is a biomolecule comprised of repeating units of inorganic phosphate residues linked by energy-rich phosphoanhydride bonds. PolyP is highly conserved throughout evolution and plays a vital role in the survival of prokaryotes and single-cell eukaryotes1 by functioning in processes such as motility, virulence and stress. Its role in mammalian systems was less well defined, however, identification of polyP in the dense granules of human platelets2 prompted analysis of the function of polyP in hemostasis. Stimulation of platelets by conventional agonists such as ADP, thrombin and collagen induces release of polyP, and promotes coagulation by acting at several points in the cascade3. These include 1) providing a surface for activation of the contact pathway protein factor XII, 2) augmenting conversion of factor V to factor Va which participates in the prothrombinase complex and 3) accelerating thrombin-mediated activation of factor XI4. The net outcome is a reduction in the lag time to thrombin formation thereby driving clot formation. The effect of polyP on thrombin generation has down-stream repercussions in terms of clot breakdown, as it augments the early activation of thrombin activatable fibrinolysis inhibitor (TAFI). There has been a degree of uncertainty and debate over whether polyP is capable of reaching adequate concentrations within the plasma milieu to elicit these profound effects on haemostasis. However, the observations that polyP can bind directly to fibrin5, allowing it to be incorporated into the forming clot, localise the biomolecule to its site of action. In addition, binding alters the structure of the fibrin clot altering its susceptibility to degradation by fibrinolytic enzymes6. These observations led to the hypothesis that polyP operates as a timed switch, being released from platelets upon activation thereby allowing rapid repair of an injury while simultaneously preventing clot breakdown until sufficient wound healing has occurred3. The ability of polyP to promote FXII-dependent coagulation has been reported in several studies but has been contested, as shorter soluble polymers, such as those found in platelets, are relatively inefficient in this process. Recent work from our group7 and others8 documents the retention of polyP on the surface of degranulated platelets. This pool of polyP is of longer chain length than the soluble secreted form and is complexed to divalent metal ions8 thereby augmenting its ability to stimulate factor XII activation. These studies highlight the potential that polyP may exert its biological cofactor activity when anchored to a surface such as platelets, fibrin and potentially other blood cells. Many questions remain as to how this polymer regulates its plethora of functions and whether the binding surface impacts on the target reaction and the half-life of the polymer. However, taken together these in vitro and in vivo studies have delineated a role for polyP in hemostasis and highlight the requirement for more efficient tools to quantify this interesting biomolecule in subsets of patients. References Kornberg A. Inorganic polyphosphate: a molecule of many functions. Prog Mol Subcell Biol. 1999;23:1-18. Ruiz FA, Lea CR, Oldfield E, Docampo R. Human platelet dense granules contain polyphosphate and are similar to acidocalcisomes of bacteria and unicellular eukaryotes. J Biol Chem. 2004;279(43):44250-44257. Smith SA, Mutch NJ, Baskar D, Rohloff P, Docampo R, Morrissey JH. Polyphosphate modulates blood coagulation and fibrinolysis. Proc Natl Acad Sci U S A. 2006;103(4):903-908. Choi SH, Smith SA, Morrissey JH. Polyphosphate is a cofactor for the activation of factor XI by thrombin. Blood. 2011;118(26):6963-6970. Whyte CS, Chernysh IN, Domingues MM, Connell S, Weisel JW, Ariens RA, Mutch NJ. Polyphosphate delays fibrin polymerisation and alters the mechanical properties of the fibrin network. Thromb Haemost. 2016;116(5):897-903. Mutch NJ, Engel R, Uitte de Willige S, Philippou H, Ariens RA. Polyphosphate modifies the fibrin network and down-regulates fibrinolysis by attenuating binding of tPA and plasminogen to fibrin. Blood. 2010;115(19):3980-3988. Mitchell JL, Lionikiene AS, Georgiev G, Klemmer A, Brain C, Kim PY, Mutch NJ. Polyphosphate colocalizes with factor XII on platelet-bound fibrin and augments its plasminogen activator activity. Blood. 2016;128(24):2834-2845. Verhoef JJ, Barendrecht AD, Nickel KF, Dijkxhoorn K, Kenne E, Labberton L, McCarty OJ, Schiffelers R, Heijnen HF, Hendrickx AP, Schellekens H, Fens MH, de Maat S, Renne T, Maas C. Polyphosphate nanoparticles on the platelet surface trigger contact system activation. Blood. 2017;129(12):1707-1717. Disclosures No relevant conflicts of interest to declare.
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Groeneveld, Dafna, David Pereyra, Zwanida Veldhuis, Jelle Adelmeijer, Petra Ottens, Anna K. Kopec, Patrick Starlinger, Ton Lisman, and James P. Luyendyk. "Intrahepatic fibrin(ogen) deposition drives liver regeneration after partial hepatectomy in mice and humans." Blood 133, no. 11 (March 14, 2019): 1245–56. http://dx.doi.org/10.1182/blood-2018-08-869057.
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AbstractPlatelets play a pivotal role in stimulating liver regeneration after partial hepatectomy in rodents and humans. Liver regeneration in rodents is delayed when platelets are inhibited. However, the exact mechanisms whereby platelets accumulate and promote liver regeneration remain uncertain. Thrombin-dependent intrahepatic fibrin(ogen) deposition was recently reported after partial hepatectomy (PHx) in mice, but the role of fibrin(ogen) deposits in liver regeneration has not been investigated. We tested the hypothesis that fibrin(ogen) contributes to liver regeneration by promoting intrahepatic platelet accumulation and identified the trigger of rapid intrahepatic coagulation after PHx. PHx in wild-type mice triggered rapid intrahepatic coagulation, evidenced by intrahepatic fibrin(ogen) deposition. Intrahepatic fibrin(ogen) deposition was abolished in mice with liver-specific tissue factor deficiency, pinpointing the trigger of coagulation after PHx. Direct thrombin activation of platelets through protease-activated receptor-4 did not contribute to hepatocyte proliferation after PHx, indicating that thrombin contributes to liver regeneration primarily by driving intrahepatic fibrin(ogen) deposition. Fibrinogen depletion with ancrod reduced both intrahepatic platelet accumulation and hepatocyte proliferation after PHx, indicating that fibrin(ogen) contributes to liver regeneration after PHx by promoting intrahepatic platelet accumulation. Consistent with the protective function of fibrin(ogen) in mice, low postoperative plasma fibrinogen levels were associated with liver dysfunction and mortality in patients undergoing liver resection. Moreover, increased intrahepatic fibrin(ogen) deposition was evident in livers of patients after liver resection but was remarkably absent in patients displaying hepatic dysfunction postresection. The results suggest a novel mechanism whereby coagulation-dependent intrahepatic fibrin(ogen) deposition drives platelet accumulation and liver regeneration after PHx.
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Okwusidi, J. I., and F. A. Ofosu. "Bioregulatory roles for fibrin(ogen) on blood coagulation." Medical Hypotheses 39, no. 2 (October 1992): 152–55. http://dx.doi.org/10.1016/0306-9877(92)90177-e.
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Moiseyev, Gilead, Sefi Givli, and Pinhas Z. Bar-Yoseph. "Fibrin polymerization in blood coagulation—A statistical model." Journal of Biomechanics 46, no. 1 (January 2013): 26–30. http://dx.doi.org/10.1016/j.jbiomech.2012.09.019.
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Johnson, Lawrence L., Kiera N. Berggren, Frank M. Szaba, Wangxue Chen, and Stephen T. Smiley. "Fibrin-mediated Protection Against Infection-stimulated Immunopathology." Journal of Experimental Medicine 197, no. 6 (March 10, 2003): 801–6. http://dx.doi.org/10.1084/jem.20021493.
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Fibrin, a product of the blood coagulation cascade, accompanies many type 1 immune responses, including delayed-type hypersensitivity, autoimmunity, and graft rejection. In those settings, fibrin is thought to exacerbate inflammation and disease. Here, we evaluate roles for coagulation during infection with Toxoplasma gondii, a pathogen whose control requires robust type 1 immunity. We establish that fibrin prevents infection-stimulated blood loss, thereby performing a protective function that is essential for survival. Remarkably, fibrin does not simply protect against vascular damage caused directly by the infectious agent, but rather, protects against hemorrhage evoked by interferon-γ, a critical mediator of type 1 immunity. This finding, to our knowledge, is the first to document a beneficial role for coagulation during type 1 immunity, and suggests that fibrin deposition protects host tissue from collateral damage caused by the immune system as it combats infection.
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Vdovin, V. M., A. P. Momot, D. A. Orekhov, I. I. Shakhmatov, N. A. Lycheva, and D. A. Momot. "Assessment of the effect of exogenous fibrin monomer on post-traumatic bleeding in hypofibrinogenemia caused by administration of snake venom Agkistrodon rhodostoma." Kazan medical journal 101, no. 5 (October 27, 2020): 704–12. http://dx.doi.org/10.17816/kmj2020-704.
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Aim. To assess the effect of fibrin monomer on the rate of blood loss after controlled liver injury in hypofibrinogenemia induced by systemic administration of Malayan pit viper venom (Agkistrodon rhodostoma).
Methods. A placebo-controlled study of the hemostatic effect of fibrin monomer administered intravenously at 0.25 mg/kg, and coagulation parameters in the controlled liver injury with profound hypofibrinogenemia caused by administration of Malayan pit viper venom was conducted in 34 male Chinchilla rabbits. The distribution of the studied parameters was investigated by the ShapiroWilk test. Statistical differences between groups were tested by Students t-test, MannWhitney U test, or Wilcoxon test, as appropriate. Differences in mortality rate were examined using Fisher's exact test.
Results. A model of experimental toxogenic disseminated intravascular coagulation was reproduced, manifested by high mortality of animals (50.0%), severe blood loss (increased blood loss by 1.78 times), hemolysis, a decreased platelet count (by 19.6% of median) and platelet dysfunction, fibrinogen consumption (protein content less than 0.9 g/l), hypocoagulation as well as intensive D-dimer production (increased concentration by 25.0 times of median). A high level of the fibrin derivative demonstrated activation of fibrin formation and fibrinolysis in the bloodstream of the animals. Systemic prophylactic administration of exogenous fibrin monomer after receiving snake venom did not lead to a decrease in post-traumatic bleeding, whereas earlier, during reproduction of disseminated intravascular coagulation caused by streptokinase infusion, such a hemostatic effect of fibrin monomer was shown.
Conclusion. The absence of fibrin monomer effect (at a dose of 0.25 mg/kg) on the severity of blood loss in toxogenic disseminated intravascular coagulation may be associated with more profound disseminated intravascular coagulation and a sharp 25-fold increase in D-dimer levels that can act as a fibrin monomer polymerization inhibitor.
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Walsh, Peter N., and Syed S. Ahmad. "Proteases in blood clotting." Essays in Biochemistry 38 (October 1, 2002): 95–111. http://dx.doi.org/10.1042/bse0380095.
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The serine proteases, cofactors and cell-receptor molecules that comprise the haemostatic mechanism are highly conserved modular proteins that have evolved to participate in biochemical reactions in blood coagulation, anticoagulation and fibrinolysis. Blood coagulation is initiated by exposure of tissue factor, which forms a complex with factor VIIa and factor X, which results in the generation of small quantities of thrombin and is rapidly shutdown by the tissue factor pathway inhibitor. The generation of these small quantities of thrombin then activates factor XI, resulting in a sequence of events that lead to the activation of factor IX, factor X and prothrombin. Sufficient thrombin is generated to effect normal haemostasis by converting fibrinogen into fibrin. The anticoagulant pathways that regulate blood coagulation include the protein C anticoagulant mechanism, the serine protease inhibitors in plasma, and the Kunitz-like inhibitors, tissue factor pathway inhibitor and protease nexin 2. Finally, the fibrinolytic mechanism that comprises the activation of plasminogen into plasmin prevents excessive fibrin accumulation by promoting local dissolution of thrombi and promoting wound healing by reestablishment of blood flow.
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Fickenscher, Karl, Angela Aab, and Werner Stüber. "A Photometric Assay for Blood Coagulation Factor XIII." Thrombosis and Haemostasis 65, no. 05 (1991): 535–40. http://dx.doi.org/10.1055/s-0038-1648185.
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SummaryAn assay for a direct photometric determination of F XIII in untreated and undiluted plasma was developed. In a one-step procedure F XIII is activated by thrombin and Ca2+ and crosslinks glycine-ethylester to a specific glutamine containing peptide substrate. The released ammonia is incorporated into α-keto-glutarate by glutamate dehydrogenase, and the NADH consumption of this reaction is measured photometrically at 340 nm. NADH-consumption is directly proportional to the F XIII activity. Fibrin polymerization and the corresponding turbidity is avoided by the use of a fibrin aggregation inhibitor.The procedure is rapid and simple and enables to measure within the range of 0 to 150% F XIII. It can be performed with automated analyzers as well as with common photometric equipment.The normal range of F XIII activity in 167 healthy donors was determined to be 70 to 140%.
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Rijken, Dingeman C., and Shirley Uitte de Willige. "Inhibition of Fibrinolysis by Coagulation Factor XIII." BioMed Research International 2017 (2017): 1–6. http://dx.doi.org/10.1155/2017/1209676.
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The inhibitory effect of coagulation factor XIII (FXIII) on fibrinolysis has been studied for at least 50 years. Our insight into the underlying mechanisms has improved considerably, aided in particular by the discovery that activated FXIII cross-linksα2-antiplasmin (α2AP) to fibrin. In this review, the most important effects of different cross-linking reactions on fibrinolysis are summarized. A distinction is made between fibrin-fibrin cross-links studied in purified systems and fibrin-α2AP cross-links studied in plasma or whole blood systems. While the formation ofγchain dimers in fibrin does not affect clot lysis, the formation ofαchain polymers has a weak inhibitory effect. Only strong cross-linking of fibrin, associated with high molecular weightαchain polymers and/orγchain multimers, results in a moderate inhibition fibrinolysis. The formation of fibrin-α2AP cross-links has only a weak effect on clot lysis, but this effect becomes strong when clot retraction occurs. Under these conditions, FXIII preventsα2AP being expelled from the clot and makes the clot relatively resistant to degradation by plasmin.
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Chudzinski-Tavassi, Ana Marisa, Eva Maria Kelen, Ana Paula de Paula Rosa, Stephane Loyau, Claudio Sampaio, Cassian Bon, and Eduardo Anglés-Cano. "Fibrino(geno)lytic Properties of Purified Hementerin, a Metalloproteinase from the Leech Haementeria depressa." Thrombosis and Haemostasis 80, no. 07 (1998): 155–60. http://dx.doi.org/10.1055/s-0037-1615155.
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SummaryThe fibrino(geno)lytic protein designated hementerin contained in crude extracts of the salivary complex of Haementeria depressa leeches was purified to apparent homogeneity by gel filtration, ion exchange chromatography and preparative SDS-PAGE. It is a single-chain 80 kDa, PhMeSO2F-resistant, calcium-dependent, metalloproteinase, which specifically degrades fibrin(ogen) through a plasminogen-independent pathway. The amino terminal sequence of 8 residues shows 80% similarity with hementin, another fibrino(geno)lytic protein purified from Haementeria ghilianii leeches. However, their activities differ somewhat in terms of kinetics and with regard to the structure of the fibrin(ogen) fragments they may produce. Cleavage by hementerin of fibrinogen Aα, γ and Bβ chains, in that order, produces 270 kDa to 67 kDa fragments which differ from those produced by plasmin. Hementerin was also able to degrade cross-linked fibrin although at a lower rate as compared to fibrinogen. In conclusion, hementerin is a plasminogen-independent fibrino(geno)lytic metalloproteinase that degrades fibrinogen faster than fibrin, prevents blood coagulation and destroys fibrin clots in vitro.
Dissertations / Theses on the topic "Fibrin Blood coagulation"
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Badiei, Nafisheh. "Microstructural and rheological studies of fibrin-thrombin gels." Thesis, Swansea University, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.678597.
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Curtis, Daniel Jonathan. "Rheological and microstructural studies of biopolymer systems." Thesis, Swansea University, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.678405.
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Swanepoel, A. C. (Albe Carina). "Ultrstructural and flow cytometric analysis of platelets and fibrin networks during the menstrual cycle and pregnancy." Thesis, University of Pretoria, 2013. http://hdl.handle.net/2263/32969.
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INTRODUCTION: The menstrual cycle and pregnancy are processes unique to women. Both these processes involve various hormones as well as the coagulation system. Throughout normal pregnancy, platelet activation and increase in blood coagulation factors contributes to the hypercoagulable state observed on a physiological level. METHODS: Fibrin networks and platelets were analysed by electron microscopy and flow cytometry to determine any differences found in different phases of pregnancy compared to healthy control individuals. The fibrin networks from different phases of the menstrual cycle as well as different phases of pregnancy were investigated. RESULTS: It was found that ultrastructural changes in fibrin fiber morphology result from estrogen changes during the menstrual cycle. During pregnancy the minor thin fibers were prominent and thick matted layers of coagulant formation were evident. A large quantity of protein globular clusters similar to those seen in the menstrual cycle was present. Changes observed in platelet ultrastructure during pregnancy showed pregnancy-specific modifications. Platelets were activated and internal organelles showed variation from control participants. Flow cytometric analysis of platelets verified pregnancy-specific modifications. Close interactions between platelets and erythrocytes were evident. CONCLUSION: The female body is equipped to handle alterations in the coagulation system as can be extrapolated from the pregnancy-specific modifications. This study is the first to show alterations in fibrin network and platelet ultrastructure during and after pregnancy when compared to non-pregnant controls. The physiological changes during normal pregnancy can be used as a standard for comparison to abnormal or ailing pregnancy.Thesis (PhD)--University of Pretoria, 2013.
gm2013
Physiology
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Plag, Camille. "Exploration ultrasonore haute-fréquence de la coagulation sanguine : cinétique des transformations microstructurelles lors de la fibrinoformation et de la contraction plaquettaire." Thesis, Tours, 2012. http://www.theses.fr/2012TOUR3306.
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Actuellement, l'étude exploratoire de la fonction hémostatique en routine se fonde essentiellement sur les tests du bilan standard d'hémostase, c'est à dire la détermination du temps caractéristique de formation d'un gel de fibrine dans des conditions standardisées. Cependant, la dernière décennie a vu la naissance de nouveaux tests se focalisant sur les transformations mécaniques du sang lors de sa coagulation. Portés par les récentes avancées dans la connaissance des phénomènes biochimiques et biophysiques menant à ces transformations mécaniques, ces tests, basés sur une étude dynamique des propriétés viscoélastiques de la coagulation du sang total, sont aujourd'hui de plus en plus adoptés par les hématologues et sont au centre d'un nombre grandissant d'études cliniques. C'est dans ce contexte que, s'appuyant sur les récents développements des techniques ultrasonores haute-fréquence, un dispositif de monitoring ultrasonore haute-fréquence de la coagulation sanguine sur sang total a été développé au sein de notre équipe. Grâce à une analyse simultanée de plusieurs paramètres acoustiques, ce dispositif à montré ses capacités à suivre les transformations mécaniques du sang coagulant. Le travail de cette thèse a consisté à poursuivre le développement de ce dispositif en s'attachant notamment à discriminer le rôle respectif des différents phénomènes ayant lieu lors de la coagulation sur les cinétiques acoustiques mesurées. En analysant les effets de traitements anticoagulant et anti-agrégant plaquettaires sur notre monitoring ultrasonore dans le cadre d'une étude clinique pilote, un premier potentiel diagnostic du dispositif a été établi. Les résultats de cette étude ont ensuite mené à la mise en place de mesures spécifiques centrées sur deux phénomènes : la formation de la fibrine et la contraction plaquettaire. Une visualisation originale de la formation du réseau de fibrine a pu être mise en place et a mené à la détermination d'un nouveau paramètre capable de déterminer à la fois le temps de gélification et le temps de rétraction. La gélification du milieu s'est avéré être primordiale dans l'évolution de l'atténuation dans le milieu, tout comme la rétraction du caillot est essentiellement responsable de l'augmentation de la vitesseToday, routine blood coagulation tests rely principally on the measurement of the time for a blood sample to gel under standardized conditions. However, in the last decade, new tests focused on monitoring mechanical changes during blood coagulation have been developped. Thanks to a new understanding of the biochemical and biophysical phenomena leading to those mechanical changes, these tests, dynamically studying the viscoelastic properties of coagulating whole blood, tend to be more and more adopted by haematologists and are the focus of a tremendous amount of clinical studies. Within this context and due to the recent development of high-frequency ultrasound techniques, a high-frequency ultrasound apparatus allowing the monitoring of whole blood coagulaion has been developped by our team. Simultaneously analysing the kinetics of four acoustical parameters, it has shown its potential in monitoring the mechanical changes appearing in whole blood coagulation. In this PhD thesis, new developments of this technique have been carried out and allowed to discriminate the respective role of the different phenomena appearing during coagulation on our acoustical parameters. Analysing the effect of anticoagulant and antiplatelet therapy within a pilot clincal study, the diagnostic potential of our test has been established. Following the results of this study, specific measurements have been set up and have shown the importance of two phenomena : fibrin formation and platelet contraction. A new way to visualize the fibrin network formation has been devised and has led to the computation of a new parameter capable of defining gel time and retraction time. Gelation of the medium was shown to be linked to the changes in attenuation in the medium and retraction of the clot was found to be critical in the rise of longitudinal velocity
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Antovic, Aleksandra. "Determinations of the overall haemostasis potential and fibrin gel permeability : method development and application in research and in clinical materials /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-932-3/.
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Ellery, Paul E. R. "Expression and modulation of tissue factor and tissue factor pathway inhibitor in an endothelial cell based model." Curtin University of Technology, School of Biomedical Sciences, 2008. http://espace.library.curtin.edu.au:80/R/?func=dbin-jump-full&object_id=18719.
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Haemostasis is a complex physiological process involving cellular and plasma protein components that interact to keep the blood fluid under normal conditions and prevent blood loss after vessel injury by promoting clot formation. Primary haemostasis encompasses the activation and aggregation of platelets and is supported by secondary haemostasis, in which the coagulation factors of the plasma interact in a complex series of reactions. Secondary haemostasis is initiated by the exposure of tissue factor (TF) to the blood after vessel injury. TF forms a complex with activated factor VII (FVIIa), which in turn activates factor X (FXa) and ultimately results in fibrin formation. The TF-FVIIa complex and FXa are tightly regulated by tissue factor pathway inhibitor (TFPI), a trivalent Kunitz-type protease inhibitor. The endothelium, consisting of endothelial cells (ECs), constitutes the inner lining of all blood vessels. As such, it is in constant contact with the blood and plays a major role in haemostasis by synthesising and storing both pro- and anti- coagulant substances, including TF and TFPI. Release of TFPI from ECs is increased after exposure to both unfractionated and low molecular weight heparins, though the mechanisms are not clearly defined. TFPI circulates in plasma, predominantly bound to lipoproteins, though the effect of the three major lipoproteins [low density (LDL), very low density (VLDL) and high density (HDL)] on the release of TFPI from ECs is not well established. Furthermore, previous studies have not systematically investigated the effect of these lipoproteins on both TF and TFPI. The initial aim of this project was to establish assays for the measurement of TF activity and TFPI antigen to supplement the TFPI activity assay that is well established in our laboratory.These assays were then used to determine the effects of heparin and the major lipoproteins on the expression of TF and the release of TFPI on/from ECs. Human umbilical vein endothelial cells (HUVECs) were used as the EC model because their collection and isolation is well established and they have biochemical and physiological properties representative of in vivo conditions. A TF activity assay, based on a previously published method, was successfully modified and validated for the measurement of cell surface TF (standard curve R2 = 0.997). Despite exhaustive attempts, adaptation of this assay for plasma TF was unsuccessful, raising doubts regarding the plasma fractionation procedure of the originally published assay [Fukuda, C., Iijima, K. and Nakamura, K. (1989). "Measuring tissue factor (factor III) activity in plasma." Clinical Chemistry 35(9): 1897â€1900]. A novel insect cell expression system was used to produce well defined recombinant TFPI standards for use in TFPI activity and antigen assays. For the first time, truncated TFPI variants, containing the first Kunitz domain only, the first and second Kunitz domains only, and the first through third Kunitz domains minus the carboxyl terminus, were successfully produced in insect cells, though the full length molecule was not. Possible reasons for this include codon bias, protein instability and/or the signal peptide used. An ELISA to measure TFPI antigen was designed using a monoclonal antiâ€TFPI antibody directed against the Nâ€terminus for protein capture and a polyclonal anti†TFPI antibody for detection. The assay was successfully optimised (standard curve R2 = 0.978, intraâ€assay CV = 4.8%), however it produced inaccurate results (normal range = 498.7 ± 156.3 ng/mL), probably due to the antibody combination used.
TF and TFPI activity assays were used to determine the effect of both unfractionated and low molecular weight heparins (UFH and LMWH, respectively) on the release of TFPI and the expression of TF from/on ECs. A significant increase in the secretion of functional TFPI from ECs due to heparin (0 U/ml vs 1 and 10 U/mL) was demonstrated only in the presence of serum (UFH: 9.0 mU/mL vs 18.3 and 18.4 mU/mL, p < 0.0001; LMWH: 8.8 mU/mL vs 13.3 and 21.4 mU/mL, p < 0.05), suggesting, for the first time, that a component of serum is required for the heparinâ€dependent release of TFPI. The effect of LDL, VLDL and HDL on the release of TFPI and the expression of TF from/on ECs was also investigated. All three lipoprotein fractions increased the secretion of functional TFPI after one hour incubation (LDL: 12.5 μg/mL, p < 0.01; 25 μg/mL, p < 0.05; VLDL: 50 μg/mL, p < 0.01; HDL: 50 μg/mL, p < 0.05). This is the first data to demonstrate a HDLâ€dependent increase in released TFPI. After 24 hours, both LDL and VLDL decreased levels of secreted functional TFPI (LDL: 25 μg/mL, p < 0.01; 50 μg/mL, p < 0.01; VLDL: 12.5 μg/mL, p < 0.01), probably due to the oxidation and subsequent association of both lipoprotein species with TFPI. Surprisingly, both LDL and VLDL decreased cell surface TF, though this effect was not dose dependent. These results suggest that the major lipoproteins have a short term anticoagulant effect which is reversed in the longer term due to lipid oxidation. In summary, this thesis describes the successful adaptation of a chromogenic assay for the measurement of cell surface TF activity and the production of truncated TFPI variants.
Both will be used for the measurement of TF and TFPI, their association with thrombus formation and propagation, and investigations into potential therapeutic applications of TFPI. The results presented in this thesis extend the current knowledge on the expression and release of TF and TFPI on/from ECs by heparin, highlighting the importance of serum in the heparin dependent release of TFPI in vitro. Furthermore, it describes for the first time the effects of the major lipoprotein fractions on TFPI release and TF expression. The data support novel mechanisms by which LDL and VLDL are procoagulant, and HDL anticoagulant. This study provides a foundation for future research of the TF pathway in cellular models, which is critical in increasing the understanding of the pathogenesis and treatment of thrombotic disease. vitro. Furthermore, it describes for the first time the effects of the major lipoprotein fractions on TFPI release and TF expression. The data support novel mechanisms by which LDL and VLDL are procoagulant, and HDL anticoagulant. This study provides a foundation for future research of the TF pathway in cellular models, which is critical in increasing the understanding of the pathogenesis and treatment of thrombotic disease.
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Barrett, Brandon J. "Molecular and rheological characterization of hyaluronic acid : determination of its role in thrombin-catalyzed fibrin clotting and viscosupplementation of joints." Thesis, 2002. http://hdl.handle.net/1957/31641.
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Three samples of the biopolymer hyaluronic acid (HA) were characterized in the
following manner: the molecular weights were obtained via multi-angle laser light
scattering; the intrinsic viscosities were calculated through dilute solution
viscometry, and the rheology of HA solutions was determined with constant rate
rotational viscometry and dynamical mechanical testing.
In addition, the highly debated role of hyaluronic acid in wound healing was
examined by studying the effect that HA has upon thrombin-catalyzed fibrin
clotting. Fibrin, in phosphate-buffered saline, was clotted both alone and after
being incubated with HA. It was determined that the presence of hyaluronic acid
resulted in a slower clotting process; in effect, HA acts as an anti-coagulant. Based
upon the experimental evidence, it is proposed that this anti-coagulant phenomenon
arises through a combination of two mechanisms: 1) specific binding between HA
and fibrin, which acts to retard fibrin clotting through steric hindrance, and 2) the
formation of an HA network which slows fibrin clotting by hindering free diffusion
of fibrin and thrombin.
Finally, creation of a synthetic replacement for synovial fluid was attempted using
xanthan gum and locust bean gum in phosphate-buffered saline. The phenomenon
of gum synergism was utilized in an effort to exert some degree of fine-tuning over
the final rheological properties of the solution. This also would provide the side
benefit of reducing the weight of gum required per unit volume. By mixing the
solutions at different temperatures, it was possible to exploit the tendency of
xanthan gum to uncoil at higher temperatures and therefore bind more strongly to
locust bean gum. However, it was determined that no combination of gum
concentrations and processing conditions resulted in a gum solution that adequately
mimicked the rheology of a hyaluronan solution.Graduation date: 2003
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Velha, Laís Domingues. "The evolution of autologous platelet concentrates : a narrative review." Master's thesis, 2020. http://hdl.handle.net/10400.14/31084.
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Purpose of the study: The goal of the study was to perform a general overview of the evolution of the autologous platelet concentrates (APC) and present the understanding of the different protocols and their benefits in clinical application and for patients in Dentistry. Development: With the advancement of science as well as laboratory tests in the context of platelet concentrates, it was possible to create protocols for autologous concentrates without the need for blood manipulation with astringent, called platelet-rich fibrin (PRF). With the development of the low-speed centrifugation concept, several protocols have been investigated and established, registering in its composition a greater number of cells of interest for tissue regeneration. Conclusion: The evolution of the APC and the different protocols arose with the need to improve these processes in the recruitment of cells of interest for better tissue regeneration.Objetivo do estudo: O objetivo do estudo foi realizar uma visão geral da evolução dos concentrados de plaquetas autólogas (APC) e apresentar o entendimento dos diferentes protocolos e seus benefícios na aplicação clínica e para pacientes em Medicina Dentária. Desenvolvimento: Com o avanço da ciência, bem como testes de laboratório no contexto de concentrados de plaquetas, foi possível criar protocolos para concentrados autólogos sem a necessidade de manipulação do sangue com adstringente, chamada fibrina rica em plaquetas (PRF). Com o desenvolvimento do conceito de centrifugação em baixa velocidade, vários protocolos foram investigados e estabelecidos, registrando em sua composição um maior número de células de interesse para a regeneração tecidual. Conclusão: A evolução da APC e os diferentes protocolos surgiram com a necessidade de melhorar esses processos no recrutamento de células de interesse para melhor regeneração tecidual.
Books on the topic "Fibrin Blood coagulation"
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Kuiper, Gerhardus J. A. J. M., and Hugo ten Cate. Coagulation monitoring. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0266.
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Haemostasis is a dynamic process to stop bleeding after vessel wall damage. Platelets form a platelet plug via activation, adherence, and aggregation processes. The coagulation proteins are activated one-by-one, cascading towards fibrin polymerization, a process controlled by thrombin generation. Fibrinolysis is the process responsible for fibrin mesh degradation, which is also controlled by thrombin. Besides procoagulant proteins, anticoagulant proteins maintain a balance in the haemostatic system. Measuring platelet count and function can be done as part of the monitoring of haemostasis, while coagulation times are measured to assess the coagulation proteins. Degradation products of fibrin and lysis times give information about fibrinolysis. Point-of-care monitoring provides simple, rapid bedside testing for platelets and for whole blood using viscoelasticity properties. In trauma-induced coagulopathy (TIC) platelet counts and coagulation times are still common practice to evaluate haemostasis, but point-of-care measurements are being used more and more. Medication interfering with haemostasis is frequently used in intensive care unit patients. Each (group of) drug(s) has its own monitoring tests either based on classical or novel techniques.
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Fibrinogen, Fibrin Stabilisation and Fibrinolysis, Clinical, Biochemical and Laboratory Aspects. VCH Publishing, 1988.
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Pruthi, Rajiv K. Coagulation (Hemostasis and Thrombosis). Oxford University Press, 2012. http://dx.doi.org/10.1093/med/9780199755691.003.0295.
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The coagulation system has 2 essential functions: to maintain hemostasis and to prevent and limit thrombosis. The procoagulant component of the hemostatic system prevents and controls hemorrhage. Vascular injury results in activation of hemostasis, which consists of vasospasm, platelet plug formation (platelet activation, adhesion, and aggregation), and fibrin clot formation (by activation of coagulation factors in the procoagulant system). The anticoagulant system prevents excessive formation of blood clots, and the fibrinolytic system breaks down and remodels blood clots. Quantitative abnormalities (deficiencies) and qualitative abnormalities of platelets and coagulation factors lead to bleeding disorders, whereas deficiencies of the anticoagulant system are risk factors for thrombosis. Common disorders of hemostasis and thrombosis are reviewed.
Book chapters on the topic "Fibrin Blood coagulation"
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Prydz, Hans. "Triggering of the extrinsic blood coagulation system." In Fibrin formation and Fibrinolysis, edited by D. A. Lane, 325–36. Berlin, Boston: De Gruyter, 1986. http://dx.doi.org/10.1515/9783110871951-036.
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Henschen, Agnes, and Jan Mcdonagh. "Chapter 7 Fibrinogen, fibrin and factor XIII." In Blood Coagulation, 171–241. Elsevier, 1986. http://dx.doi.org/10.1016/s0167-7306(08)60053-8.
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Thompson, Carrie A. "Malignant Hematologic Disorders." In Mayo Clinic Internal Medicine Board Review, 427–38. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190464868.003.0039.
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The 2 essential functions of the coagulation system (maintaining hemostasis and preventing and limiting thrombosis) are served by the procoagulant and anticoagulant components. Vascular injury results in activation of the phases of hemostasis, including vasospasm, platelet plug formation (platelet activation, adhesion, and aggregation), and fibrin clot formation (by activation of coagulation factors in the procoagulant system). The anticoagulant system controls excessive clot formation, while the fibrinolytic system breaks down and remodels blood clots.
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Warkentin, T. E. "Acquired coagulation disorders." In Oxford Textbook of Medicine, edited by Chris Hatton and Deborah Hay, 5546–62. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0547.
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Acquired disorders of coagulation may be the consequence of many underlying conditions, and although they may share abnormality of a coagulation test, for example, a prolonged prothrombin time, their clinical effects are diverse and often opposing. General clinical approach: diagnosis—most acquired disorders of coagulation can be identified by screening haemostasis tests, including (1) prothrombin time; (2) activated partial thromboplastin time; (3) thrombin clotting time; (4) fibrinogen degradation products, including (5) the cross-linked fibrin assay (D-dimer); and (6) complete blood count with examination of a blood film. Few bleeding disorders give normal results in all these tests, but disorders predisposed to thrombosis as a result of deficiency of natural anticoagulants (e.g. antithrombin, protein C, and protein S) or certain mutations (e.g. factor V Leiden) must be specifically sought. Treatment—patients with coagulopathies who are bleeding or who require surgery are usually treated with blood products such as platelets and frozen plasma. Other treatments used in particular circumstances include (1) vitamin K—required for the post-translational modification of factors II, VII, IX, and X as well as the anticoagulant factors, protein C, and protein S; (2) cryoprecipitate—used principally for the treatment of hypofibrinogenaemia; (3) concentrates of specific factors—used in isolated deficiencies (e.g. of factors VIII, IX, XI, VIIa, or fibrinogen); (4) antifibrinolytic agents (e.g. ε-aminocaproic acid and tranexamic acid); (5) desmopressin (1-deamino-8-d-arginine vasopressin)—increases factor VIII and von Willebrand factor.
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White, Gilbert C., Harold R. Roberts, and Nigel S. Key. "The biology of haemostasis and thrombosis." In Oxford Textbook of Medicine, edited by Chris Hatton and Deborah Hay, 5490–509. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0543.
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Haemostasis—a component of the wound defence mechanism—is a process by which vessel wall components and platelets act in concert with procoagulant and anticoagulant proteins to form a plug of cells and cross-linked fibrin. The plug is later remodelled and replaced by new tissue as part of wound healing. These processes are very complex and involve highly controlled pathways of interaction between cells, glycans, and membrane-bound and soluble proteins of coagulation and fibrinolysis, as well as their cognate inhibitors. Thrombosis—this is an abnormal state leading to formation of a clot that partially or completely obstructs the flow of blood within the blood vessel; dislodgement leads to thromboembolism. To understand the biology of haemostasis and thrombosis, it is necessary to know the roles of the vessel wall, the platelets, the coagulation and fibrinolytic systems, and their respective inhibitors. Fibrinolysis and coagulation are interrelated: fibrin clots are normally lysed by plasmin locally released from plasminogen by the action of tissue plasminogen activator, and this process can be enhanced by some procoagulant factors (e.g. activated factor XII, and protein C). This system, so delicately controlled and normally maintained in a dynamic equilibrium, is strongly influenced by components involved in inflammatory and other defence mechanisms in the host. An integrated understanding of these processes offers the potential for improved means to predict the adverse complications of many diseases and ultimately to prevent their occurrence.
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Li, Jie Jack. "Clopidogrel Bisulfate (Plavix)." In Top Drugs. Oxford University Press, 2015. http://dx.doi.org/10.1093/oso/9780199362585.003.0006.
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Three types of blood cells exist in the human body: red blood cells, white blood cells, and platelets. Red blood cells, 45% of the blood, transport oxygen from the lungs to other body parts. White cells, less than 1% of the blood, defend us against bacterial and viral invasions. Platelets, also less than 1% of the blood (55% of the remaining blood is plasma), are small cell fragments that are involved in helping the blood clot, a process known as blood coagulation. Coagulation takes place when the enzyme thrombin elicits platelets and fibrin, a blood protein. Without platelets, coagulation at the site of an injury does not occur and uncontrolled bleeding ensues. Individuals with no ability to clot have a genetic condition called hemophilia. These individuals must periodically administer a clotting factor to their blood to prevent constant bleeding. Conversely, thrombosis, the formation of blood clots inside blood vessels, can block coronary arteries and constrict vital oxygen supplies, resulting in a heart attack or stroke. Coronary thrombosis is a life-threatening blood clot in the artery. Deep-vein thrombosis (DVT) is commonly associated with long-distance air travel, when passengers are confined to cramped spaces for many hours. In contrast with thrombosis, in which the clot is stationary, embolus is when an object such as a clot migrates from one part of the body through blood circulation and causes blockage. A pulmonary embolism occurs when emboli travel to the lungs. Approximately 90% of heart attacks and 80% of strokes are caused by blood clots, which kill some 200,000 hospital patients in the US each year. Anticoagulants (blood thinners) are the drugs of choice to prevent and treat both thrombosis and embolism. To date, heparin, warfarin, and aspirin have all been widely used as blood thinners to prevent blood clots from forming. Heparin is one of the oldest medicines still in widespread clinical use. Heparin was extracted in 1916 by Jay McLean from dog’s liver in the laboratories of William Howell at the Johns Hopkins University.
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Storey, Robert F., and William A. Parker. "Thrombotic response." In ESC CardioMed, edited by Stefan James, 1227–30. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0308.
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Thrombosis is the central process responsible for acute coronary syndromes. Erosion or rupture of atherosclerotic plaque exposes the blood constituents to subendothelial matrix. The coagulation system is activated via contact activation (intrinsic pathway) and tissue factor release from plaque (extrinsic pathway) resulting in thrombin generation and fibrin clot formation. Platelets adhere to the subendothelial matrix and are activated by collagen and thrombin resulting in shape change, thromboxane release, degranulation, and aggregation. Activation of the platelet P2Y12 receptor and recruitment of other platelets amplifies the thrombotic response. Propagation of thrombus formation leads to coronary artery occlusion with resulting distal myocardial ischaemia or infarction, or both.
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Becker, Richard C., and Frederick A. Spencer. "Historical Perspectives in Hemostasis, Coagulation, and Fibrinolysis: A Foundation for Understanding Thrombotic Disorders and Developing Effective Treatment." In Fibrinolytic and Antithrombotic Therapy. Oxford University Press, 2006. http://dx.doi.org/10.1093/oso/9780195155648.003.0005.
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Hemostasis, the prompt cessation of bleeding at a site of vascular injury, is among the most fundamental physiologic and teleologically vital defense mechanisms in nature. Without a functionally intact hemostatic mechanism, death could ensue rapidly even after minor traumas associated with everyday life. In mammalian blood coagulation, regulated by a complex network of integrated biochemical events, five protease factors (f ) (fIIa [thrombin], fVIIa, fIXa, fXa, and protein C) interact with five cofactors (tissue factor, f VIIIa, fVa, thrombomodulin, and protein S) to regulate the generation of fibrin (Davidson et al., 2003). Although each component of the mammalian coagulation network has unique functional properties, available data based on gene organizations, protein structure, and sequence analysis suggest that it may have resulted from the reduplication and diversification of two gene structures over 400 million years ago. A vitamin K–dependent serine protease is composed of a γ-carboxylated glutamic acid (GLA) epidermal growth factor-like (EGF) 1–EGF 2-serine protease domain structure common to fVII, fIX, fX, and protein C, and the A1-A2-B-AB-C1-C2 domain structure common to fV and fVIII. Prothrombin is also a vitamin K–dependent serine protease; however, it contains kringle domains rather than EGF domains (suggesting a replacement during gene duplication and shuffling). Analyses of active site function amino acid residues reveal distinguishing characteristics of thrombin from other serine proteases, supporting its position as the ancestral blood enzyme (Krem and Cera, 2002; McLysaght et al., 2002). The rapid transformation of fluid blood to a gel-like substance (clot) has been a topic of great interest to scientists, physicians, and philosophers since the days of Plato and Aristotle ( Jewett, 1892; Lee, 1952). However, it was not until the beginning of the 18th century that blood clotting (coagulation) was appreciated as a means to stem blood loss from wounds (hemostasis) (Petit, 1731). As with other areas of science, the microscope played a pivotal role in the understanding of coagulation. In the mid-17th century, Marcello Malpighi separated the individual components of a blood clot into fibers, cells, and serum (Forester, 1956).
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Becker, Richard C., and Frederick A. Spencer. "Venous Thromboembolism." In Fibrinolytic and Antithrombotic Therapy. Oxford University Press, 2006. http://dx.doi.org/10.1093/oso/9780195155648.003.0008.
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Blood clotting within the venous circulatory system, in contrast to arterial thrombosis, occurs at a relatively slow pace in response to stagnation of flow (stasis) and activation of coagulation. As with arterial thrombosis, vascular injury, either direct in the setting of trauma or indirect as a diffuse, systemic inflammatory response (that ultimately causes endothelial cell damage), represents an important stimulus. Venous thrombi are intravascular deposits composed predominantly of erythrocytes and fibrin, with a variable contribution of platelets and leukocytes. In a majority of cases, thrombosis begins in areas of slow flow within the venous sinuses of valve cusp pockets either in the deep veins of the calf or upper thigh or at sites of direct injury following trauma (Kakkar et al., 1969; Nicolaides et al., 1971). Stasis predisposes to thrombosis most profoundly in the setting of inflammatory states and activated coagulation factors. Slowed blood flow impairs the clearance of coagulation proteases, which through bioamplification increases the local concentration of thrombin substrate. If local thromboresistance is impaired, as may be the case with inherited or acquired thrombophilias (see Chapter 24), thrombosis occurs. Blood flow velocity is reduced by indwelling catheters, which also causes focal endothelial injury, peripheral edema, pregnancy, and valve cusp damage from prior venous thrombosis and/or chronic venous insufficiency (Trottier et al., 1995). Although venous thrombosis can occur in a variety of sites, the most common encountered in clinical practice is within the deep veins of the lower extremity. Thrombi developing within the veins of the calf or thigh can serve as a nidus for growth (propagation), which may cause complete venous obstruction, or embolize to the lungs (pulmonary embolism).
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Lancellotti, Patrizio, and Stella Marchetta. "Non-bacterial thrombotic endocarditis." In ESC CardioMed, edited by Gilbert Habib, 1728–29. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0395.
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Non-bacterial thrombotic endocarditis (NBTE) is characterized by the presence of sterile vegetations on cardiac valves that consist of fibrin and platelet aggregates. These vegetations are neither associated with bacteraemia nor with destructive changes of the underlying valve. The diagnosis of NBTE relies on strong clinical suspicion in the context of (a) a disease process known to be associated with NBTE, (b) the presence of a heart murmur, (c) a negative blood culture, (d) the presence of vegetations not responding to antibiotic treatment, and (e) evidence of multiple systemic emboli. The same initial diagnostic work-up as for infective endocarditis is recommended. Serial blood cultures, exhaustive haematological and coagulation studies, and a comprehensive echocardiography should be performed. The management of NBTE is challenging and a tailored approach should be advocated. It should first focus on the underlying pathology. In the absence of contraindications, an anticoagulation treatment should be given. Surgical intervention is not recommended unless the patient has clear indications (i.e. heart failure due to valve dysfunction).
Conference papers on the topic "Fibrin Blood coagulation"
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Miura, T., M. Inagaki, M. Taki, N. Saito, T. Meguro, and K. Yamada. "GRANULOCYTE ELASTASE RELEASE DURING BLOOD COAGULATION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643166.
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Granulocyte elastase (ELP) has a high-potency fibrinolytic activity. Hence, there is a possibility that ELP acts as a thrombolytic enzyme like plasmin in thrombolysis. We investigated the release of ELP from granulocytes, especially during blood coagulation.The biological activity of ELP was measured using a synthetic substrate, Suc-Ala-Tyr-Leu-Val-pNA. The immunological activity assayed as an alpha-l-antitrypsin-ELP complex was measured using an anti-ELP antibody (Merck), because more than 90% of ELP in blood forms alpha-l-antitrypsin-ELP complexes.The ELP activity in granulocytes extracted by 2 mol/1 KSCN was 10 mU/106 cells. This fibrinolytic activity corresponds to 1-2 U of plasmin in the fibrin plate method.The ELP release from separated granulocytes was observed by adding Ca2+, and the release was increased by Ca ionophore A 23187. The release was dose-dependent as far as 10 mM Ca2+ (final concentration) and the maximum release was obtained within 15 minutes. However, the ELP release was not produced by thrombin.The level of alpha-l-antitrypsin-ELP complex in serum was twice higher and that in heparinized plasma was 1.5 times higher than that in sodium citrated plasma. ELP was not released from granulocytes incubated in both prekallikrein deficient plasma and Factor XII deficient plasma containing 10 mM Ca2+. But addition of normal plasma (about 10%) resulted in ELP releaseThese results suggest that the ELP release from granulocytes is dependent on Ca2+ and the release is relevant to the blood coagulation system, especially to contact factors.
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Weiss, H. J., V. T. Turitto, and H. R. Baumgartner. "FACTORS INFLUENCING FIBRIN DEPOSITION ON SUBENDOTHELIUM." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642950.
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During the past several years, we have initiated studies to determine the role of plasma factors and platelets, and the properties of the blood vessel, which influence the activation of the coagulation mechanism on the subendothelium. Studies were performed by exposing everted segments of de-endothelialized rabbit aorta, mounted in a perfusion chamber, to non-anticoagulated human blood for 5 to 10 minutes under a range of flow conditions, and measuring fibrin and platelet deposition on the subendothelium, and fibrinopepstide A (FPA) levels in post-chamber blood. In normal subjects, platelet deposition increased progressively with increasing shear rates (50-2600 sec-1 ), whereas fibrin deposition and FPA levels decreased sharply at shear rates greater than 650 sec-1 . To examine the role of plasma coagulation factors, we utilized a shear rate of 650 sec-1 to study patients with severe deficiencies of factors XII, XI, IX or VIII. In contrast to the partial thromboplastin time (PTT), which was most strikingly abnormal in patients with factor XII or XI deficiency, fibrin deposition and FPA levels were greater in patients deficient in factor XII or XI than in those with factor VIII or IX deficiency. In addition, we observed smaller platelet thrombi in hemophilia (but not afibrinogenemia), suggesting that thrombin influenced the formation of platelet thrombi under these shear conditions. The findings suggested that tissue factor-Vila activation of factor IX could be important in mediating fibrin deposition on subendothelium and might explain why patients with factor XII deficiency (and some with factor XI deficiency) do not bleed. Initial studies to demonstrate tissue factor activity in subendothelium were inconclusive. More recently, utilizing shorter (1.5, 2 and 3 min) perfusion periods, we have observed decreased fibrin deposition and FPA levels in patients with factor VII deficiency and we have obtained further support for the presence of tissue factor in subendothelium in experiments utilizing a monoclonal antibody to tissue factor. Our studies suggest that activation of factor IX by tissue factor-Vila could account for the results obtained in patients with plasma coagulation defects. Direct experimental verification of this hypothesis will require more extensive studies on the kinetics governing the activation of coagulatjon factors on the subendothelium. In subsequent studies, we examined the role of platelets in mediating fibrin deposition. At a shear rate of 650 sec-1 we found (utilizing patients with thrombocytopenia) that platelets were required for fibrin deposition ; little or no fibrin was deposited on the subendothelium when platelet adhesion was less than 4%, corresponding to blood platelet counts less than 5000/ul. Studies performed in patients with functional platelet disorders provided additional information on the specific platelet properties that contribute to fibrin deposition at this shear rate. Decreased fibrin deposition was observed in a patient with Scott Syndrome, a disorder characterized by an impaired capacity of the platelets to catalyze the conversion of factor X to factor Xa (in the presence of factor IXa and VIII) and prothrombin to thrombin (in the presence of factor Va), the latter defect owing to a decreased factor Xa-binding capacity of the platelets. In contrast to the findings in Scott Syndrome, both fibrin deposition and FPA values were completely normal (and possibly increased) in patients with glycoprotein Ilb/IIIa deficiency. In patients with glycoprotein lb deficiency, the major defect was an impaired association of fibrin with platelets, but not subendothelium. The findings in patients with functional platelet disorders indicate that a monolayer of platelets (including those deficient in glycoprotein Ilb/IIIa) is completely active in promoting fibrin deposition on subendothelium. In addition, they suggest that an agent capable of inducing a platelet defect similar to that observed in Scott Syndrome might prevent platelet-fibrin thrombi at shear rates (200-800 sec-1 ) comparable to those in the coronary circulation. Studies performed at a variety of shear rates in both normal subject^ and patients with platelet disorders suggested that, under the conditions used, platelets were essential for fibrin formation at intermediate (650 sec-1 ), but not low (50 sec-1 ) shear rates. Since platelets have been shown to bind activated coagulation proteins (such as factor Xa, Va, and IXa) to their surface, the presence of adherent platelets on the subendothelium could, with increasing shear rates, serve to maintain activated coagulation proteins in the .boundary layer at a concentration that would otherwise be reduced through convective diffusion in their absence. Thus, at low shear rates (50 sec-1 ), the concentration of activated coagulation factors in the boundary layer might be sufficient to support fibrin deposition despite the absence of platelets, whereas at very high shear rates (2,600 sec-1 and above), even the presence of platelets is insufficient to maintain the required concentration. The shear-dependent defect of fibrin formation that we observed in Scott Syndrome is consistent with such a theory. The results of our various studies demonstrate the complex role of blood flow, plasma coagulation factors, specific platelet properties, and the procoagulant properties (tissue factor) of the vessel in mediating subendothelium-induced coagulation and suggest further experiments for studying the mechanisms involved.
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Pourang, Sina, Debnath Maji, Ujjal D. S. Sekhon, Anirban Sen Gupta, Michael A. Suster, and Pedram Mohseni. "Monitoring Fibrin Polymerization Effects on Whole Blood Coagulation Using a Microfluidic Dielectric Sensor." In 2020 IEEE SENSORS. IEEE, 2020. http://dx.doi.org/10.1109/sensors47125.2020.9278794.
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Scheefers-Borchel, U., and G. Muller-Berghaus. "A NEW FIBRIN-SPECIFIC ANTIBODY DISCRIMINATING BETWEEN FIBRIN AND FIBRINOGEN IS DIRECTED AGAINST THE SYNTHETIC PEPTIDE LEU-ILE-ASP-GLY-LYS-MET." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643771.
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To determine soluble fibrin in blood of patients with coagulation disorders we produced monoclonal antibodies which distinct fibrin from fibrinogen and other blood constituents. Fibrin-specific monoclonal antibodies were obtained by immunizing mice with the synthetic hexapeptide Leu-Ile-Asp-Gly-Lys-Met which was covalently linked to KLH via its C-terminus. Several of the monoclonal antibodies which reacted with the hexapeptide also reacted with batroxobin-induced desAA-fibrin and thrombin-induced desAABB-fibrin, but not with fibrinogen. No reaction was observed with plasmin-induced fibrinogenolytic and fibrinolytic degradation products, respectively. The epitope recognized by these fibrin-specific antibodies is located on the αchain of fibrin and is not accessible for an antibody in native fibrinogen. One monoclonal antibody (B/H11) was used to quantify the amount of soluble fibrin in plasma of patients with a variety of coagulation disorders. This antibody could also be used to develop an ELISA based on two different fibrin-specific monoclonal antibodies. For this assay anti-fbn 17 (Scheefers- Borchel et al., Proc. Natl. Acad. Sci. USA 82: 7091, 1985) was coated onto ELISA plates. After adding plasma which contained soluble fibrin, the fibrin bound was detected by the second fibrin-specific antibody B/H^ to which biotin was covalently linked. The second antibody was probed by the addition of peroxydase conjugated streptavidin and the substrate ABTS for peroxydase. This test can be used to detect fibrin at concentrations as low as 70 ng/ml. With this assay system, it is possible to measure the amount of soluble fibrin present in plasma samples without the interference of fibrinogen which is associated with soluble fibrin.
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Woodhams, B. J., G. Candotti, and P. B. A. Kernoff. "CHANGES IN THE COAGULATION AND FIBRINOLYTIC SYSTEM DURING PREGNANCY." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644282.
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Blood samples were collected from 17 volunteers between 8-14, 26-28 and 32-34 weeks of pregnancy. Control samples were collected from 12 non-pregnant female volunteers not using oral contraceptives. All samples were assayed for fibrinopeptide A (FPA), B beta 15-42 and for cross linked D-dimer fragments. A sample was collected for measurement of the in vitro rate of generation of fibrinopeptide A from whole blood (FPA-R).These results are consistent with an increased activation of coagulation (increased FPA and shortened FPA-R) during normal pregnancy, which is compensated for by a concomitant rise in fibrinolytic activity (increased D-dimer and B beta 15-42). In 2 patients who miscarried and 2 patients who developed hypertension during pregnancy changes indicative of a non compensated hypercoagulable state could be seen. The study shows that the progress of pregnancy is associated with increased activation of coagulation and a concomitant rise in fibrin(ogen) degradation products. This data shows that a combination of these tests may be capable of detecting changes in the haemostatic balance that occur before the onset of clinical signs of gynaecological problems.
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Berk, H. R., and H. Clark. "SHEAR AND FIBRIN CLOT FORMATION; ROLE OF FPB RELEASE." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643317.
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It is well known that flow conditions affect many aspects of hemostasis. These effects range from gross morphological differences of thrombi formed at different flow rates to platelet activation to lysis. In addition, fibrin degradation products can influence blood flow. This investigation concerns itself with the effect of shear on the later stages of fibrin polymerization.Fibrinogen (human, Kabi) is reacted with thrombin (human, Sigma) under Couette flow conditions (volume-averaged shear 0-250 sec-1) in a pH 6.8, 4mM CaC12 HEPES buffered solution (I.S.-.15). Reaction times are chosen to achieve 30% FPA removal for various IT], Reptilase and Crotalase. Low Reynolds number hydrodynamic theory is used to investigate theoretical effects of shear on fibrils.The effect of shear on final clot formation is measured in terms of clot mass (%Pt). The effects of shear on orientation, diffusion and coagulation on the protofibril-fibril stage account for the initial decrease in %Pt at low shear. It is determined that the shear at which %Pt reaches a minimum (Gcrit) is thrombin concentration dependent. Lateral aggregation of fibrils is identified as the critical variable, with fibril breakage accounting for the increase in %Pt with increasing shear. The theory that fibrin formation proceeds by oligomer-oligomer addition is supported.Using hydrodynamic theory, a relationship betv/een axial ratio and Gcrit is obtained (assuming tensional or buckling failure). Using a hypothetical relationship between thrombin concentration and fiber axial ratio, a theoretical Gcrit versus IT] is obtained. This theoretical relationship is similar to that obtained experimentally, supporting the notion of shear induced breakage.Calcium is shown to increase Gcrit for a given [T]Experiments with Crotalase and Reptilase implicate FPB removal as an important factor in the minimum position. This provides an important insight into the significance of FPB removal in in vivo clot formation and shear stability.
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David, J. L., M. Lambrichts, and M. T. Closon. "INFRACLINIC ACTIVATION OF PLATELETS AND FIBRIN FORMATION IN CANCER PATIENTS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643198.
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Thromboembolism has been frequently reported in cancer patients, mainly in cases with solid tumors. Besides in several animal models, fibrin deposition around the tumor and platelet aggre gates appear to be involved in invasion and metastasis. This study was aimed at evaluating the extent of in vivo platelet activation and fibrin formation in several kinds of human cancer. We excluded from this study patients whose blood was sampled with difficulty as well as those having clinical evidence of thrombosis or embolism, those with thrombocytopenia, increased fibrinogen degradation products or biological pattern of disseminated intravascular coagulation. Fibrinopeptide A (fpA) and β-thrombo-globulin (β-tg) were determined by RIA. Free platelet count ratio (PCR) was determined on whole blood samples as an index of circulating aggregates. Usual coagulation tests, antithrombin III activity, protein C plasma level, F VIII related antigen (F VIII RAG), F VIII Ristocetin cofactor (F VIII RCF) and F VIII procoagulant activity (F VIII C) were also determined.It was found that in more than fifty percent of patients, fpA was significantly increased above the upper reference limit. Cases with increased B-tg were less frequent. Separate increases in β-tg or fpA levels were often observed. PCR remained within the reference values in almost all patients. F VIII RAG, RCF and C were usually above 150 % of the reference mean.We conclude that platelet release and fibrinoformation frequently occur in cancer patients showing no sign of thrombotic process. Increased level of fpA with normal plasma β-tg level suggests that thrombin generation occurs only in the extravascular compart ment, probably next to the tumoral tissues. Increased levels of plasma β-tg with normal fpA levels may result from platelet activation by other stimuli than thrombin. It must be emphasized that normal PCR does not exclude the presence of fibrinous circulating aggregates which cannot be dispersed by EDTA. High F VIII activities may be due to the release of the von Willebrand factor from tumoral vessels.
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Basciano, Christopher A., Julie H. Y. Ng, Ender A. Finol, and Clement Kleinstreuer. "A Relation Between Particle Hemodynamics and Intraluminal Thrombus Formation in Abdominal Aortic Aneurysms." In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-204721.
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Abdominal aortic aneurysms (AAAs) are local dilations of the aorta below the renal arteries where the lumen diameter is ≥ 1.5 times the normal diameter of the healthy blood vessel. Ruptured aneurysms are the 13th leading cause of death in the US [1]. In approximately 75% of all AAAs, a particle-deposition layer forms adjacent to the arterial wall within the lumen called the intra-luminal thrombus (ILT). The thrombus composition has been shown to be a fibrin structure composed of blood cells, platelets, blood proteins, and other cellular debris [2]. Additionally, Yamazumi et al. [3] have presented data that suggest AAA morphology is associated with an elevated state of blood coagulation and fibrinolysis within the aneurysm.
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Bartsch, P., A. Haeberli, and P. W. Straub. "NORMAL FIBRINOPEPTTDE A (FPA) AND ELEVATED FIBRINOGEN DEGRADATION PRODUCTS AFTER LONG DISTANCE RUNNING." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643132.
Full textAbstract:
Physical exercise leads to a shortening of activated partial thrcnboplastin time (PIT) and euglobulin lysis time (ELT). Whether this activation causes in-vivo thrombin and plasmin action remains controversial however. 19 well trained long distance runners were examined 25 min (range 5-53) after termination of a 100 km race (post-race values) run in 577 min (457-755) and 5 days later after at least one day without physical exercise (control values). FPA, platelet factors and fibrin (ogen) split products (fragment E and BB 15-42) were measured with radioimnunoassays. ELT was assessed before and after venous occlusion (VO). The table gives mean values ±SD:Thrombin time, platelet count, platelet factor 4 and haematocrit did not change significantly. FPA was normal in all post-race samples and did not correlate significantly with the time lag between arrival and blood sampling, indicating that activation of blood coagulation in exhaustive physical exercise of long duration does not lead to in-vivo fibrin formation. Activation of fibrinolysis, however, results in circulating plasmin activity as demonstrated by the elevation of the fibrin (ogen) degradation products fragment E and BB 15-42. Since the polyclonal antibodies used in the latter assay crossreact with BB 1-42, these results alone do not allow to jjdge whether plasmin degrades fibrin or fibrinogen. However, lack of fibrin formation suggests fibrinogenolysis rather than fibrinolysis.
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Aurousseau, M. H., V. Eclache, and J. Amiral. "CLINICAL RELEVANCE OF D.DIMER AND COAGULATION INHIBITORS IN LIVER CIRRHOSIS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643140.
Full textAbstract:
D.Dimer was measured by a latex agglutination assay and an enzyme immunoassay (E.I.A.) in 25 patients suffering from liver cirrhosis. High levels of D.Dimer (> 500 ng/ml) were found in 13/25 patients’ plasma, by the latex test as well as EIA. Fibrinogen Degradation Products (FDP), measured by the Merskey method, were present in 7/25 samples, whereas soluble fibrin monomer complexes were only detected in 2/25 patients. In both cases, D.Dimer was elevated and FDP were in the normal range. Only one patient developped a Disseminated Intravascular Coagulation (DIC). None of the others had any thromboembolic event.Anticoagulant plasma proteins, Protein C (pC), total and free Protein S (pS) and Antithrombin III (AT III), were measured, in these patients, using the Laurell method.Mean values measured were :AT III : 50 % ± 16 total pS : 69 % ± 20pC : 38 % ± 28 free pS : 63 % ± 30Using immunoassays, pS showed the lowest decrease, in comparison to the other coagulation inhibitors.These values were compared to some procoagulant activities : prothrombin, factors VII ± X and factor V.4 good correlation was observed between AT III and prothrombin (r = 0.752 p < 0.01), whereas a poorer one was obtained between pC and factors VII and X (r = 0.455 p < 0.02). There was no correlation between pC and pS, nor between pC and factor V. Despite marked decrease of coagulation inhibitors in liver cirrhosis, low incidence of thrombotic accidents was observed (1/25) probably due to a parallel decreased synthesis of procoagulant factors. However, an in vivo blood activation associated to a reactive fibrinolysis was evidenced by measurement of pathological levels of D.Dimer in 13/25 patients. In this way, D.Dimer is a more sensitive and specific marker, than total FDP, to evaluate blood activation in liver cirrhosis. D.Di Test allows a rapid estimation and gives similar results to the EIA method.