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Journal articles on the topic 'Proteins in blood coagulation'
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1
SUZUKI, KOJI. "Blood coagulation control proteins." Nihon Naika Gakkai Zasshi 83, no. 4 (1994): 646–53. http://dx.doi.org/10.2169/naika.83.646.
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Patthy, László. "Evolutionary Assembly of Blood Coagulation Proteins." Seminars in Thrombosis and Hemostasis 16, no. 03 (July 1990): 245–59. http://dx.doi.org/10.1055/s-2007-1002677.
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Xu, Li-Chong, James W. Bauer, and Christopher A. Siedlecki. "Proteins, platelets, and blood coagulation at biomaterial interfaces." Colloids and Surfaces B: Biointerfaces 124 (December 2014): 49–68. http://dx.doi.org/10.1016/j.colsurfb.2014.09.040.
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Sonawani, Archana, Pravin Nilawe, Ram Shankar Barai, and Susan Idicula-Thomas. "ClotBase: a knowledgebase on proteins involved in blood coagulation." Blood 116, no. 5 (August 5, 2010): 855–56. http://dx.doi.org/10.1182/blood-2010-04-282616.
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Gryshchuk, Volodymyr, and Natalya Galagan. "Silica Nanoparticles Effects on Blood Coagulation Proteins and Platelets." Biochemistry Research International 2016 (2016): 1–6. http://dx.doi.org/10.1155/2016/2959414.
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Interaction of nanoparticles with the blood coagulation is important prior to their using as the drug carriers or therapeutic agents. The aim of present work was studying of the primary effects of silica nanoparticles (SiNPs) on haemostasisin vitro. We studied the effect of SiNPs on blood coagulation directly estimating the activation of prothrombin and factor X and to verify any possible effect of SiNPs on human platelets. It was shown that SiNPs shortened coagulation time in APTT and PT tests and increased the activation of factor X induced by RVV possibly due to the sorption of intrinsic pathway factors on their surface. SiNPs inhibited the aggregation of platelet rich plasma induced by ADP but in the same time partially activated platelets as it was shown using flow cytometry. The possibility of SiNPs usage in nanomedicine is strongly dependant on their final concentration in bloodstream and the size of the particles that are used. However SiNPs are extremely promising as the haemostatic agents for preventing the blood loss after damage.
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HANSSON, K., and J. STENFLO. "Post-translational modifications in proteins involved in blood coagulation." Journal of Thrombosis and Haemostasis 3, no. 12 (December 2005): 2633–48. http://dx.doi.org/10.1111/j.1538-7836.2005.01478.x.
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Harlos, K., S. K. Holland, C. W. G. Boys, A. I. Burgess, M. P. Esnouf, and C. C. F. Blake. "Vitamin K-dependent blood coagulation proteins form hetero-dimers." Nature 330, no. 6143 (November 1987): 82–84. http://dx.doi.org/10.1038/330082a0.
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Shibeko, A. M., A. N. Balandina, N. A. Podoplelova, and M. A. Panteleev. "Current trends in blood coagulation studies." Pediatric Hematology/Oncology and Immunopathology 19, no. 3 (October 9, 2020): 144–50. http://dx.doi.org/10.24287/1726-1708-2020-19-3-144-150.
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Blood coagulation occurs in flow or stasis conditions, it involves components of cell hemostasis and enzymatic cascades of reactions; it serves to stop bleeding yet it can lead to life-threatening blood thrombi. Despite the fact that a complete list of coagulation proteins was well known for decades, in recent years numerous facts has accumulated about its structure and regulation. All that has led to the creation of new methods for diagnosing of blood coagulation disorders and methods for their correction. Congenital and acquired coagulation disorders are still an acute clinical problem. This review shows modern ideas about the structure and functioning of the blood coagulation system in various conditions.
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Engelmann, Beatrice, Julia Bischof, Anne-Luise Dirk, Nele Friedrich, Elke Hammer, Thomas Thiele, Dagmar Führer, Georg Homuth, Georg Brabant, and Uwe Völker. "Effect of Experimental Thyrotoxicosis onto Blood Coagulation: A Proteomics Study." European Thyroid Journal 4, Suppl. 1 (2015): 119–24. http://dx.doi.org/10.1159/000381769.
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Background: Hyperthyroidism is known to induce a hypercoagulable state. It stimulates plasma levels of procoagulative factors and reduces fibrinolytic activity. So far most of the data have been derived from patients with endogenous hyperthyroidism with a wide variability in the underlying pathogenesis and severity of the disease. Objectives: In this study we experimentally induced thyrotoxicosis in healthy volunteers to explore the effects of thyroxine excess on the plasma proteome. Using a shotgun proteomics approach, the abundance of plasma proteins was monitored before, during and after thyrotoxicosis. Methods: Sixteen healthy male subjects were sampled at baseline, 4 and 8 weeks under 250 µg/day thyroxine p.o., as well as 4 and 8 weeks after stopping the application. Plasma proteins were analyzed after depletion of 6 high-abundance proteins (MARS6) by LC-ESI-MS/MS mass spectrometry. Mass spectrometric raw data were processed using a label-free, intensity-based workflow. Subsequently, the linear dependence between protein abundances and fT4 levels were calculated using a Pearson correlation. Results: All subjects developed biochemical thyrotoxicosis, and this effect was reversed within the first 4 weeks of follow-up. None of the volunteers noticed any subjective symptoms. Levels of 10 proteins involved in the coagulation cascade specifically correlated with fT4, supporting an influence of thyroid hormone levels on blood coagulation even at nonpathological levels. Conclusions: The results suggest that experimental thyrotoxicosis exerts selective and specific thyroxine-induced effects on coagulation markers. Our study design allows assessment of thyroid hormone effects on plasma protein levels without secondary effects of other diseases or therapies.
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Vannakambadi, Ganesh, Magnus Höök, Pietro Speziale, and Jose Rivera. "Fibrinogen-binding proteins of Gram-positive bacteria." Thrombosis and Haemostasis 98, no. 09 (2007): 503–11. http://dx.doi.org/10.1160/th07-03-0233.
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SummaryFibrinogen (Fg), the major clotting protein in blood plasma, plays key roles in blood coagulation and thrombosis. In addition, this 340 kD glycoprotein is a stress inducible protein; its synthesis is dramatically upregulated during inflammation or under exposure to stress such systemic infections.This regulation of Fg expression indicates that Fg also participates in the host defense system against infections. In fact, a number of reported studies have demonstrated the involvement of both the intrinsic and extrinsic pathways of coagulation; the thrombotic and the fibrinolytic systems in the pathophysiology of infectious diseases. It is, therefore, perhaps not surprising that many pathogenic bacteria can interact with Fg and manipulate its biology.This review focuses on the major Fg-binding proteins (Fgbps) from Gram-positive bacteria with an emphasis on those that are known to have an effect on coagulation and thrombosis
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Noubouossie, Denis F., Matthew F. Whelihan, Yuan-Bin Yu, Erica Sparkenbaugh, Rafal Pawlinski, Dougald M. Monroe, and Nigel S. Key. "In vitro activation of coagulation by human neutrophil DNA and histone proteins but not neutrophil extracellular traps." Blood 129, no. 8 (February 23, 2017): 1021–29. http://dx.doi.org/10.1182/blood-2016-06-722298.
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Key Points Individual histone proteins and DNA purified from normal human neutrophils promote coagulation activation. Neither intact NETs nor nucleosomes directly promote coagulation activation in plasma in vitro.
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Einersen, Peter, Sanchayita Mitra, Reid Selby, Ernest E. Moore, Marguerite Kelher, Miguel Fragoso, Daran Schiller, et al. "Liver X Receptor (LXR) Is a Novel and Reversible Regulator of Trauma-Induced Coagulopathy." Blood 136, Supplement 1 (November 5, 2020): 2. http://dx.doi.org/10.1182/blood-2020-143292.
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Trauma-induced coagulopathy (TIC) manifests as a bimodal disruption of normal fibrinolysis, where at the two extremes, fibrinolytic shutdown (TICFS) places the patient at increased risk for thromboembolism and post-injury multiple organ failure, and systemic hyperfibrinolysis (TICHF) results in excessive bleeding. Plasma proteomic profiles for 65 trauma patients were used to identify changes in the patient's plasma protein profile stratifying them by risk for TIC. A strong correlation was seen between total plasma protein concentration of individual patients and the concentration of coagulation proteins within that patient, suggesting that trauma-induced coagulation may be affected through a mechanism that controls the efflux of many coagulation proteins into the plasma (Figure 1). Pathway analysis, in addition to elucidating changes in the coagulation cascade, identified several proteins that are known to be regulated by the Liver X receptor/Retinoid X receptor (LXR/RXR), suggesting that LXR/RXR-mediated activity may regulate TIC (p=9.03E-26). Validation experiments in a rat model revealed that fibrinolytic response to an LXR antagonist and/or agonist can be observed in less than 60 minutes (Figure 2). Additionally, we show through reciprocal rescue of fibrinolysis that the TIC phenotypes (TICHF and TICFS) are one continuum and are ultimately co-reversible, where the reduced LXR signaling that causes sequestration of blood factors in the liver leading to excess bleeding or induced LXR signaling that causes excess efflux leading to thrombosis can be reversed through administration of the LXR agonist or antagonist, respectively. Thus, as modulation of LXR shows co-reversibility and rapid response, induction/inhibition of the LXR pathway provides a direct and novel therapeutic intervention in severely injured patients at risk for TIC. Disclosures No relevant conflicts of interest to declare.
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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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Villoutreix, B. O. "Structural Bioinformatics: Methods, Concepts and Applications to Blood Coagulation Proteins." Current Protein and Peptide Science 3, no. 3 (June 1, 2002): 341–64. http://dx.doi.org/10.2174/1389203023380657.
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Benzakour, Omar. "Vitamin K-dependent proteins: Functions in blood coagulation and beyond." Thrombosis and Haemostasis 100, no. 10 (2008): 527–29. http://dx.doi.org/10.1160/th08-07-0497.
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Rohrbach, F., B. Pötzsch, J. Müller, and G. Mayer. "Aptamer-based modulation of blood coagulation." Hämostaseologie 31, no. 04 (2011): 258–63. http://dx.doi.org/10.5482/ha-1156.
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SummaryNucleic acid based aptamers are singlestranded oligonucleotide ligands isolated from random libraries by an in-vitro selection procedure. Through the formation of unique three-dimensional structures, aptamers are able to selectively interact with a variety of target molecules and are therefore also promising candidates for the development of anticoagulant drugs. While thrombin represents the most prominent enzymatic target in this field, also aptamers directed against other coagulation proteins and proteases have been identified with some currently being tested in clinical trials.In this review, we summarize recent developments in the design and evaluation of aptamers for anticoagulant therapy and research.
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Butera, Diego, Kristina M. Cook, Joyce Chiu, Jason W. H. Wong, and Philip J. Hogg. "Control of blood proteins by functional disulfide bonds." Blood 123, no. 13 (March 27, 2014): 2000–2007. http://dx.doi.org/10.1182/blood-2014-01-549816.
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Abstract Most proteins in nature are chemically modified after they are made to control how, when, and where they function. The 3 core features of proteins are posttranslationally modified: amino acid side chains can be modified, peptide bonds can be cleaved or isomerized, and disulfide bonds can be cleaved. Cleavage of peptide bonds is a major mechanism of protein control in the circulation, as exemplified by activation of the blood coagulation and complement zymogens. Cleavage of disulfide bonds is emerging as another important mechanism of protein control in the circulation. Recent advances in our understanding of control of soluble blood proteins and blood cell receptors by functional disulfide bonds is discussed as is how these bonds are being identified and studied.
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Vaziri, N. D., D. H. Smith, R. L. Winer, M. A. Weber, E. C. Gonzales, and J. M. Neutel. "Coagulation and inhibitory and fibrinolytic proteins in essential hypertension." Journal of the American Society of Nephrology 4, no. 2 (August 1993): 222–28. http://dx.doi.org/10.1681/asn.v42222.
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Arterial hypertension (HTN) increases the risk of cerebral coronary, and other vascular complications that frequently involve platelet activation and blood coagulation. Several key proteins in the blood coagulation, fibrinolytic and inhibitory systems were studied in 29 men with HTN (aged 45 +/- 3 yr) and 15 normal men of the same age. Plasma levels of high-molecular-weight kininogen and factors XII, IX, VII, X, II, and XIII, as well as von Willebrand factor (vWF), fibrinogen, fibronectin, alpha 2-antiplasmin, tissue-plasminogen activator, D-dimer, platelet factor-4, and protein C were measured by the use of appropriate functional and immunologic assays before and after a cardiopulmonary exercise stress test. The concentrations of vWF, alpha 2-antiplasmin, and D-dimer were significantly (P < 0.02) higher in the HTN group as compared with the control group. The exercise stress test resulted in significant rises in the plasma vWF, alpha 2-antiplasmin, and tissue-plasminogen activator levels in the two groups. The concentrations of vWF and D-dimer were related to diastolic blood pressure (r = 0.44 and 0.40, respectively; P < 0.02). Levels of vWF also were related to left ventricular mass index and left ventricular posterior wall and septal thickness (r = 0.34, 0.43, and 0.34, respectively; P < 0.05). The constellation of these findings suggests a low-grade fibrin formation and degradation, the magnitude of which is related to the diastolic blood pressure. The observed abnormalities can potentially contribute to the cardiovascular complications of untreated HTN.
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Dahlberg, Sofia, Ulf Schött, Emilia Ängeby Eriksson, Yllnor Tahirsylaj, Leon Schurgers, and Thomas Kander. "Intravenous Vitamin K1 for the Correction of Prolonged Prothrombin Times in Non-Bleeding Critically Ill Patients: A Prospective Observational Study." Nutrients 13, no. 8 (July 27, 2021): 2580. http://dx.doi.org/10.3390/nu13082580.
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The aim of this study was to evaluate the effects of vitamin K1 on various vitamin K-dependent proteins in critically ill patients with prolonged Owren PT. We included critically ill non-bleeding adult patients without liver failure or anticoagulation treatment, with Owren PT > 1.2, who were prescribed intravenous vitamin K1. Blood was drawn at baseline and at 20–28 h after vitamin K1 administration. At both time points, we measured various vitamin K-dependent proteins and coagulation assays. ClinicalTrials.gov; Identifier: NTC3782025. In total, 52 patients were included. Intravenous vitamin K1 reduced Owren PT, Quick PT, protein induced by vitamin K absence/antagonist-II and desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), but not to normal levels. Concomitantly, there were increases in thrombin generation and the activity of coagulation factors II, VII, IX and X that was only counteracted with a small increase in Protein C activity. In conclusion, the results suggest that vitamin K1 strengthens coagulation as measured by PT decrease and increases in the activity of vitamin K-dependent clotting factors and thrombin generation. The decreased dp-ucMGP, and its potential positive short- and long-term non-coagulative effects, merits further research.
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Reverdiau-Moalic, P., B. Delahousse, G. Body, P. Bardos, J. Leroy, and Y. Gruel. "Evolution of blood coagulation activators and inhibitors in the healthy human fetus." Blood 88, no. 3 (August 1, 1996): 900–906. http://dx.doi.org/10.1182/blood.v88.3.900.900.
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Abstract Blood coagulation proteins were determined in 285 healthy fetuses from 19 to 38 weeks' gestation and compared with those of 60 normal full- term newborns and 40 adult controls. Prolongation of the coagulation screening tests, prothrombin time, activated partial prothrombin time, and thrombin clotting time, in fetuses throughout intrauterine life was explained by low levels of vitamin K-dependent factors (II, VII, IX, and X), contact factors (XI, XII, prekallikrein, and high-molecular- weight kininogen), factor V, factor VIII, and fibrinogen. Low levels of antithrombin III, heparin cofactor II, protein C and protein S, and tissue factor pathway inhibitor were also found, and these probably contributed to a satisfactory hemostatic balance. Some of these parameters were evaluated by both immunologic and functional assays to detect possible “fetal” proteins. An increase in factor levels was observed after the thirty-fourth week of intrauterine life for most of the coagulation activators and inhibitors, but only factors V and VIII reached adult values at birth. This study therefore showed that fetal hemostasis is a dynamic system that evolves gradually toward the neonatal state and then toward the adult state.
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Reverdiau-Moalic, P., B. Delahousse, G. Body, P. Bardos, J. Leroy, and Y. Gruel. "Evolution of blood coagulation activators and inhibitors in the healthy human fetus." Blood 88, no. 3 (August 1, 1996): 900–906. http://dx.doi.org/10.1182/blood.v88.3.900.bloodjournal883900.
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Blood coagulation proteins were determined in 285 healthy fetuses from 19 to 38 weeks' gestation and compared with those of 60 normal full- term newborns and 40 adult controls. Prolongation of the coagulation screening tests, prothrombin time, activated partial prothrombin time, and thrombin clotting time, in fetuses throughout intrauterine life was explained by low levels of vitamin K-dependent factors (II, VII, IX, and X), contact factors (XI, XII, prekallikrein, and high-molecular- weight kininogen), factor V, factor VIII, and fibrinogen. Low levels of antithrombin III, heparin cofactor II, protein C and protein S, and tissue factor pathway inhibitor were also found, and these probably contributed to a satisfactory hemostatic balance. Some of these parameters were evaluated by both immunologic and functional assays to detect possible “fetal” proteins. An increase in factor levels was observed after the thirty-fourth week of intrauterine life for most of the coagulation activators and inhibitors, but only factors V and VIII reached adult values at birth. This study therefore showed that fetal hemostasis is a dynamic system that evolves gradually toward the neonatal state and then toward the adult state.
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Davie, E. W., A. Ichinose, and S. P. Leytus. "Structural Features of the Proteins Participating in Blood Coagulation and Fibrinolysis." Cold Spring Harbor Symposia on Quantitative Biology 51 (January 1, 1986): 509–14. http://dx.doi.org/10.1101/sqb.1986.051.01.062.
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Chen, Hsiu-Hui, Cristina P. Vicente, Li He, Douglas M. Tollefsen, and Tze-Chein Wun. "Fusion proteins comprising annexin V and Kunitz protease inhibitors are highly potent thrombogenic site-directed anticoagulants." Blood 105, no. 10 (May 15, 2005): 3902–9. http://dx.doi.org/10.1182/blood-2004-11-4435.
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AbstractThe anionic phospholipid, phosphatidyl-l-serine (PS), is sequestered in the inner layer of the plasma membrane in normal cells. Upon injury, activation, and apoptosis, PS becomes exposed on the surfaces of cells and sheds microparticles, which are procoagulant. Coagulation is initiated by formation of a tissue factor/factor VIIa complex on PS-exposed membranes and propagated through the assembly of intrinsic tenase (factor VIIIa/factor IXa), prothrombinase (factor Va/factor Xa), and factor XIa complexes on PS-exposed activated platelets. We constructed a novel series of recombinant anticoagulant fusion proteins by linking annexin V (ANV), a PS-binding protein, to the Kunitz-type protease inhibitor (KPI) domain of tick anticoagulant protein, an aprotinin mutant (6L15), amyloid β-protein precursor, or tissue factor pathway inhibitor. The resulting ANV-KPI fusion proteins were 6- to 86-fold more active than recombinant tissue factor pathway inhibitor and tick anticoagulant protein in an in vitro tissue factor–initiated clotting assay. The in vivo antithrombotic activities of the most active constructs were 3- to 10-fold higher than that of ANV in a mouse arterial thrombosis model. ANV-KPI fusion proteins represent a new class of anticoagulants that specifically target the anionic membrane-associated coagulation enzyme complexes present at sites of thrombogenesis and are potentially useful as antithrombotic agents.
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Schulz, Christian, Nina V. Leuschen, Thomas Fröhlich, Michael Lorenz, Susanne Pfeiler, Christian A. Gleissner, Elisabeth Kremmer, et al. "Identification of novel downstream targets of platelet glycoprotein VI activation by differential proteome analysis: implications for thrombus formation." Blood 115, no. 20 (May 20, 2010): 4102–10. http://dx.doi.org/10.1182/blood-2009-07-230268.
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Abstract Platelets play a key role in hemostasis and various diseases including arterial thrombosis. Glycoprotein VI (GPVI) mediates adhesion to collagen structures exposed at sites of vascular injury and subsequent platelet activation. We determined the effects of specific activation of GPVI on the human platelet proteome. Isolated human platelets were stimulated with an activating monoclonal antibody specific for GPVI. Platelet proteins were analyzed by 2-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry. We identified 8 differentially abundant proteins associated with cell signaling, metabolism, organization and rearrangement of the cytoskeleton, and membrane trafficking. Differentially abundant proteins included aldose reductase (AR), beta-centractin, charged multivesicular body protein 3, Src substrate cortactin, ERp57, and pleckstrin. Importantly, GPVI-modulated protein abundance was functionally relevant. Correspondingly, AR enzyme activity significantly increased upon GPVI activation and inhibition of AR resulted in reduced platelet aggregation. Furthermore, ERp57 was released upon ligation of platelet GPVI and increased the activity of tissue factor, a major initiator of blood coagulation. In summary, GPVI activation results in differential changes in abundance of platelet proteins, including AR and ERp57, which support platelet aggregation and platelet-dependent coagulation. These results provide further insight into the mechanisms that underlie platelet activation through the GPVI receptor and may help to identify novel pharmacologic targets.
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Preston, Roger J. S., Orla Rawley, Eimear M. Gleeson, and James S. O’Donnell. "Elucidating the role of carbohydrate determinants in regulating hemostasis: insights and opportunities." Blood 121, no. 19 (May 9, 2013): 3801–10. http://dx.doi.org/10.1182/blood-2012-10-415000.
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Recent improvement in modern analytical technologies has stimulated an explosive growth in the study of glycobiology. In turn, this has lead to a richer understanding of the crucial role of N- and O-linked carbohydrates in dictating the properties of the proteins to which they are attached and, in particular, their centrality in the control of protein synthesis, longevity, and activity. Given their importance, it is unsurprising that both gross and subtle defects in glycosylation often contribute to human disease pathology. In this review, we discuss the accumulating evidence for the significance of glycosylation in mediating the functions of the plasma glycoproteins involved in hemostasis and thrombosis. In particular, the role of naturally occurring coagulation protein glycoforms and inherited defects in carbohydrate attachment in modulating coagulation is considered. Finally, we describe the therapeutic opportunities presented by new insights into the role of attached carbohydrates in shaping coagulation protein function and the promise of carbohydrate modification in the delivery of novel therapeutic biologics with enhanced functional properties for the treatment of hemostatic disorders.
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Murashko, A. V., Yuliya S. Drapkina, and N. S. Koroleva. "The course of pregnancy and blood coagulation system." V.F.Snegirev Archives of Obstetrics and Gynecology 3, no. 4 (December 15, 2016): 181–87. http://dx.doi.org/10.18821/2313-8726-2016-3-4-181-187.
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Pregnancy represents the procoagulant state, giving rise in the high prevalence rate of thrombotic complications. An imbalance between coagulation and anticoagulation systems of blood during pregnancy can lead to the development of pre-eclampsia, intrauterine growth retardation, preterm labor, premature rupture offetal membranes and fetal death. These complications are mostly caused by the impaired generation of thrombin as well as changes in the concentration and activity of tissue factor TFPI (tissue factor pathway inhibitor), TAT III complex and protein Z. Nevertheless, it should be noted that the thrombotic complications during pregnancy depend not on the elevation of the concentrations of specific coagulation factors or lack of the activity of anticoagulant proteins, but on the shift in the whole system toward the procoagulant state. These disorders most of all lead to thromboses ofplacental vessels, causing disorders ofperfusion of the affected area. Placental pathology can develop as from the maternal as from the fetal side. Despite the fact that changes in the blood coagulation system occur from the very beginning of pregnancy, and often are adaptive in nature, i.e., do not require special medical intervention, the prompt diagnosis and treatment of hemostatic disorders as main pathogenetic link in the development of thrombosis is extremely important.
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Lisman, Ton, Marco Platto, Joost C. M. Meijers, Elizabeth B. Haagsma, Michele Colledan, and Robert J. Porte. "The hemostatic status of pediatric recipients of adult liver grafts suggests that plasma levels of hemostatic proteins are not regulated by the liver." Blood 117, no. 6 (February 10, 2011): 2070–72. http://dx.doi.org/10.1182/blood-2010-08-300913.
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Abstract Plasma levels of coagulation factors differ profoundly between adults and children, but are remarkably stable throughout adulthood. It is unknown which factors determine plasma levels of coagulation factors in a given individual. We hypothesized that the liver, which synthesizes coagulation factors, also controls plasma levels. We measured a panel of coagulation factors in samples taken from either adults or young children who underwent a liver transplantation with adult donor livers. Samples were taken 1-3 months after transplantation, when the patients were clinically stable with adequate graft function. After liver transplantation, the hemostatic profile of the pediatric group was remarkably different from that of the adult group, and resembled the hemostatic profile of normal children. Thus, children transplanted with an adult liver graft maintain a pediatric hemostatic profile after transplantation despite receiving an adult liver graft. These findings suggest that plasma levels of hemostatic proteins are not controlled by the liver.
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Dahlbäck, Björn. "Advances in understanding pathogenic mechanisms of thrombophilic disorders." Blood 112, no. 1 (July 1, 2008): 19–27. http://dx.doi.org/10.1182/blood-2008-01-077909.
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AbstractVenous thromboembolism is a major medical problem, annually affecting 1 in 1000 individuals. It is a typical multifactorial disease, involving both genetic and circumstantial risk factors that affect a delicate balance between procoagulant and anticoagulant forces. In the last 50 years, the molecular basis of blood coagulation and the anticoagulant systems that control it have been elucidated. This has laid the foundation for discoveries of both common and rare genetic traits that tip the natural balance in favor of coagulation, with a resulting lifelong increased risk of venous thrombosis. Multiple mutations in the genes for anticoagulant proteins such as antithrombin, protein C, and protein S have been identified and constitute important risk factors. Two single mutations in the genes for coagulation factor V (FV Leiden) and prothrombin (20210G>A), resulting from approximately 20 000-year-old mutations with subsequent founder effects, are common in the general population and constitute major genetic risk factors for thrombosis. In celebration of the 50-year anniversary of the American Society of Hematology, this invited review highlights discoveries that have contributed to our present understanding of the systems that control blood coagulation and the genetic factors that are involved in the pathogenesis of venous thrombosis.
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Pant, Asmita, Anna K. Kopec, and James P. Luyendyk. "Role of the blood coagulation cascade in hepatic fibrosis." American Journal of Physiology-Gastrointestinal and Liver Physiology 315, no. 2 (August 1, 2018): G171—G176. http://dx.doi.org/10.1152/ajpgi.00402.2017.
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Liver is the primary source of numerous proteins that are critical for normal function of the blood coagulation cascade. Because of this, diseases of the liver, particularly when affiliated with severe complications like cirrhosis, are associated with abnormalities of blood clotting. Although conventional interpretation has inferred cirrhosis as a disorder of uniform bleeding risk, it is now increasingly appreciated as a disease wherein the coagulation cascade is precariously rebalanced. Moreover, prothrombotic risk factors are also associated with a more rapid progression of fibrosis in humans, suggesting that coagulation proteases participate in disease pathogenesis. Indeed, strong evidence drawn from experimental animal studies indicates that components of the coagulation cascade, particularly coagulation factor Xa and thrombin, drive profibrogenic events, leading to hepatic fibrosis. Here, we concisely review the evidence supporting a pathologic role for coagulation in the development of liver fibrosis and the potential mechanisms involved. Further, we highlight how studies in experimental animals may shed light on emerging clinical evidence, suggesting that beneficial effects of anticoagulation could extend beyond preventing thrombotic complications to include reducing pathologies like fibrosis.
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De Lio, Ashley M., Riya Jain, Divyani Paul, James H. Morrissey, and Taras V. Pogorelov. "Charge Drives Initiation and Regulation of Blood Coagulation Cascade: Ions and Proteins." Biophysical Journal 118, no. 3 (February 2020): 556a—557a. http://dx.doi.org/10.1016/j.bpj.2019.11.3041.
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Bajaj, S. Paul. "Region of Factor IXa Protease Domain that Interacts with Factor VIIIa: Analysis of Select Hemophilia B Mutants." Thrombosis and Haemostasis 82, no. 08 (1999): 218–25. http://dx.doi.org/10.1055/s-0037-1615836.
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IntroductionThe identification of coagulation factor IX as a substance required for blood coagulation was first established by Pavlovsky, who reported that a mixture of blood from two hemophiliacs clotted normally.1 Based on this discovery and subsequent observations,2 hemophilia was divided into two conditions-hemophilia A or factor VIII deficiency, the most prevalent condition, and hemophilia B or factor IX deficiency, a less common condition. Since then, much has been learned about the molecular and structural biology of factor IX. It is a vitamin K-dependent protein that participates in the middle phase of the intrinsic as well as the extrinsic coagulation cascade.3 The gene for factor IX consists of eight exons and seven introns, is approximately 34 kb long, and located on the long arm of the X-chromosome at band Xq27.1.4,5 The positions of the introns in the factor IX gene are essentially identical to those of the other three homologous proteins, namely, factor VII, factor X, and protein C;3 the genes for the latter three proteins, however, are not located on the X-chromosome.
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Zubairova, L. D., I. G. Mustafin, and R. M. Nabiullina. "Pathogenetic approach to venous thrombosis markers examination." Kazan medical journal 94, no. 5 (October 15, 2013): 685–91. http://dx.doi.org/10.17816/kmj1920.
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The review summarizes experimental and clinical findings decrypting the mechanisms that initiate venous thrombosis. It is still relevant to consider the pathogenesis of venous thrombosis within the frames of the classic Virchow’s triad, and the mechanisms of interrelation of its separate mechanisms - changes in blood composition, blood flow, or alterations of the blood vessel wall - becomes more clear. Changes in the blood constituents include the amount and functional state of proteins and hemostasis system cells. Among the important changes in blood flow are blood flow rate, affecting the cells and coagulation proteins transport to the site and from the site of thrombosis, and the local shear stress, modulating adhesion and procoagulant activity of endothelium and platelets. Vascular wall provides tissue factor, which is the initiator of blood coagulation; phospholipid surface of cell membranes and microvesicles for assembling coagulation enzyme complexes, as well as adhesion proteins for the blood platelets and leukocytes «capturing». Decreased venous blood outflow and stasis, causing the local hypoxia, are associated with procoagulant changes in blood cells: the expression of P-selectin on endothelium increases, leading to the accumulation of leukocytes and cell microvesicles containing the initiator of blood coagulation - tissue factor. The local concentration of activated clotting factors increases, which along with anticoagulant activity alterations initiates progressing fibrin formation and thrombogenesis. Marking out the key mechanisms allows using them as the potential markers for diagnosing venous thrombosis risk. Among them are cell derived microparticles, cytokines, P-selectin that are investigated as possible indicators of deep vein, pulmonary, cancer associated thrombosis.
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Levi, Marcel, and Marie Scully. "How I treat disseminated intravascular coagulation." Blood 131, no. 8 (February 22, 2018): 845–54. http://dx.doi.org/10.1182/blood-2017-10-804096.
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Abstract Disseminated intravascular coagulation (DIC) is a condition characterized by systemic activation of coagulation, potentially leading to thrombotic obstruction of small and midsize vessels, thereby contributing to organ dysfunction. At the same time, ongoing consumption of platelets and coagulation proteins results in thrombocytopenia and low concentrations of clotting factors, which may cause profuse hemorrhagic complications. DIC is always secondary to an underlying condition, such as severe infections, solid or hematologic malignancies, trauma, or obstetric calamities. A reliable diagnosis of DIC can be made through simple scoring algorithms based on readily available routine hemostatic parameters. The cornerstone of supportive treatment of this coagulopathy is management of the underlying condition. Additionally, administration of heparin may be useful, and restoration of physiological anticoagulants has been suggested, but has not been proven successful in improving clinically relevant outcomes so far. In patients with major bleeding or at risk for hemorrhagic complications, administration of platelet concentrates, plasma, or coagulation factor concentrates should be considered.
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Chatrou, M. L. L., C. P. Reutelingsperger, and L. J. Schurgers. "Role of vitamin K-dependent proteins in the arterial vessel wall." Hämostaseologie 31, no. 04 (2011): 251–57. http://dx.doi.org/10.5482/ha-1157.
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SummaryVitamin K was discovered early last century at the same time as the vitamin K-antagonists. For many years the role of vitamin K was solely ascribed to coagulation and coagulation was thought to be involved only at the venous blood side. This view has dramatically changed with the discovery of vitamin K-dependent proteins outside the coagulation cascade and the role of coagulation factors at the arterial side. Vitamin K-dependent proteins are involved in the regulation of vascular smooth muscle cell migration, apoptosis, and calcification. Vascular calcification has become an important independent predictor of cardiovascular disease. Vitamin K-antagonists induce inactivity of inhibitors of vascular calcification, leading to accelerated calcification. The involvement of vitamin K-dependent proteins such as MGP in vascular calcification make that calcification is amendable for intervention with high intake of vitamin K. This review focuses on the effect of vitamin K-dependent proteins in vascular disease.
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Eberhart, Robert C., Hsiao-Hwei Huo, and Kevin Nelson. "Cardiovascular Materials." MRS Bulletin 16, no. 9 (September 1991): 50–54. http://dx.doi.org/10.1557/s0883769400056062.
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The search for biocompatible cardiovascular materials has gone on for more a century, beginning with the metallic and glass blood vessel substitutes of Alexis Carrel. The quest has become more involved as the need for flexible polymeric materials became apparent, and as knowledge has been gained about the reactions of blood with artificial surfaces. Current materials in clinical practice are, for the most part, standard polymers that have been in incardiovascular materials is thrombosis, a combination of the coagulation of the blood proteins (which traps red cells, thus obstructing vessel channels) and the activation and deposition of blood platelets, cells that rapidly aggregate with other platelets to obstruct the channel. Coagulation and platelet aggregation are interdependent, highly volatile processes, acting like two positive feedback cascade amplification processes. Thrombosis is prevented in clinical practice by administering heparin, ity. The endothelial cell releases heparin and heparan sulfate, natural anticoagulants, in response to various external stimuli. Endothelial cells produce prostacyclin, which prevents platelet activation by surface contact and is also a powerful, shortacting vasodilator. Prostacyclin release is modulated by fluid shear stresses on the endothelial membrane, among other stimuli. Endothelial cells bind the coagulation enzyme thrombin to thrombomodulin, one of the endothelial membrane proteins, removing it from circulation but also enhancing the activation of protein C, another circulating protein which inhibits blood coagulation. Creation of a material that would precisely mimic all functions of the endothelial cell is a daunting task. Fortunately, more prosaic materials exist that may be purified or modified to elicit minimal biological responses. Progress in developing these materials will be discussed in the context of typical cardiovascular devices.
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Walsh, Peter. "Platelets and Factor XI Bypass the Contact System of Blood Coagulation." Thrombosis and Haemostasis 82, no. 08 (1999): 234–42. http://dx.doi.org/10.1055/s-0037-1615838.
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IntroductionFactor XI is a plasma glycoprotein (concentration ∼30 nM) that was first identified by Rosenthal et al1 as a plasma coagulation factor deficiency in patients with abnormal hemostasis, particularly common among Ashkenazi Jews.2,3 In spite of recent advances in our understanding of the structure of factor XI and its gene, the structure-function relationships of the protein, and the molecular genetics of factor XI deficiency, considerable confusion about the physiologic role and clinical relevance of factor XI has arisen from both clinical and biochemical observations. One problem arises from the fact that, until recently, the only known pathway for activation of factor XI involved proteolytic activation by factor XIIa and interactions with coagulation proteins of the contact phase of blood coagulation.4-7 The problem arose from the clinical observation that patients with deficiencies of factor XI are subject to bleeding complications, whereas patients with deficiencies of the contact proteins are not.2,3,8-13 A related unanswered question concerns the lack of correlation in many reported patients between plasma levels of factor XI and the severity of clinical bleeding manifestations.2,3,8,9,13-15 In addition, some patients with severe factor XI deficiency experience significant bleeding complications, whereas others appear to be hemostatically normal. These clinical and biochemical observations have motivated investigations focused on alternative mechanisms for activation of factor XI independent of contact phase protein.19-22 Additional studies have focused on the identification and characterization of platelet factor XI, which is postulated to be an alternative splicing product of the factor XI gene. Platelet factor XI is present in platelet membranes and might substitute for plasma factor XI in hemostasis and account for the absence of bleeding complications in some patients with severe plasma factor XI deficiency.14,16-18,23-26 Studies addressing these two important and related problems are presented and discussed in this chapter.
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Bevers, Edouard, Theo Lindhout, and Johan Heemskerk. "Platelet Activation and Blood Coagulation." Thrombosis and Haemostasis 88, no. 08 (2002): 186–93. http://dx.doi.org/10.1055/s-0037-1613209.
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SummaryPlatelet activation and blood coagulation are complementary, mutually dependent processes in haemostasis and thrombosis. Platelets interact with several coagulation factors, while the coagulation product thrombin is a potent platelet-activating agonist. Activated platelets come in a procoagulant state after a prolonged elevation in cytosolic [Ca2+]i. Such platelets, e. g. when adhering to collagen via glycoprotein VI, expose phosphatidylserine (PS) at their outer surface and produce (PS-exposing) membrane blebs and microvesicles. Inhibition of aminophospholipid translocase and activation of phospholipid scramblase mediate the exposure of PS, whereas calpain-mediated protein cleavage leads to membrane blebbing and vesiculation. Surface-exposed PS strongly propagates the coagulation process by facilitating the assembly and activation of tenase and prothrombinase complexes. Factor IXa and platelet-bound factor Va support these activities. In addition, platelets can support the initiation phase of coagulation by providing binding sites for prothrombin and factor XI. They thereby take over the initiating role of tissue factor and factor VIIa in coagulation activation.
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Miao, Hongzhi Z., Nongnuch Sirachainan, Lisa Palmer, Phillip Kucab, Michael A. Cunningham, Randal J. Kaufman, and Steven W. Pipe. "Bioengineering of coagulation factor VIII for improved secretion." Blood 103, no. 9 (May 1, 2004): 3412–19. http://dx.doi.org/10.1182/blood-2003-10-3591.
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Abstract Factor VIII (FVIII) functions as a cofactor within the intrinsic pathway of blood coagulation. Quantitative or qualitative deficiencies of FVIII result in the inherited bleeding disorder hemophilia A. Expression of FVIII (domain structure A1-A2-B-A3-C1-C2) in heterologous mammalian systems is 2 to 3 orders of magnitude less efficient compared with other proteins of similar size compromising recombinant FVIII production and gene therapy strategies. FVIII expression is limited by unstable mRNA, interaction with endoplasmic reticulum (ER) chaperones, and a requirement for facilitated ER to Golgi transport through interaction with the mannose-binding lectin LMAN1. Bioengineering strategies can overcome each of these limitations. B-domain-deleted (BDD)-FVIII yields higher mRNA levels, and targeted point mutations within the A1 domain reduce interaction with the ER chaperone immunoglobulin-binding protein. In order to increase ER to Golgi transport we engineered several asparagine-linked oligosaccharides within a short B-domain spacer within BDD-FVIII. A bioengineered FVIII incorporating all of these elements was secreted 15- to 25-fold more efficiently than full-length FVIII both in vitro and in vivo. FVIII bioengineered for improved secretion will significantly increase potential for success in gene therapy strategies for hemophilia A as well as improve recombinant FVIII production in cell culture manufacturing or transgenic animals. (Blood. 2004;103: 3412-3419)
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Kini, R. Manjunatha. "Anticoagulant proteins from snake venoms: structure, function and mechanism." Biochemical Journal 397, no. 3 (July 13, 2006): 377–87. http://dx.doi.org/10.1042/bj20060302.
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Over the last several decades, research on snake venom toxins has provided not only new tools to decipher molecular details of various physiological processes, but also inspiration to design and develop a number of therapeutic agents. Blood circulation, particularly thrombosis and haemostasis, is one of the major targets of several snake venom proteins. Among them, anticoagulant proteins have contributed to our understanding of molecular mechanisms of blood coagulation and have provided potential new leads for the development of drugs to treat or to prevent unwanted clot formation. Some of these anticoagulants exhibit various enzymatic activities whereas others do not. They interfere in normal blood coagulation by different mechanisms. Although significant progress has been made in understanding the structure–function relationships and the mechanisms of some of these anticoagulants, there are still a number of questions to be answered as more new anticoagulants are being discovered. Such studies contribute to our fight against unwanted clot formation, which leads to death and debilitation in cardiac arrest and stroke in patients with cardiovascular and cerebrovascular diseases, arteriosclerosis and hypertension. This review describes the details of the structure, mechanism and structure–function relationships of anticoagulant proteins from snake venoms.
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Pavlou, Efthimia G., Hara T. Georgatzakou, Sotirios P. Fortis, Konstantina A. Tsante, Andreas G. Tsantes, Efrosyni G. Nomikou, Athanasia I. Kapota, et al. "Coagulation Abnormalities in Renal Pathology of Chronic Kidney Disease: The Interplay between Blood Cells and Soluble Factors." Biomolecules 11, no. 9 (September 4, 2021): 1309. http://dx.doi.org/10.3390/biom11091309.
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Coagulation abnormalities in renal pathology are associated with a high thrombotic and hemorrhagic risk. This study aims to investigate the hemostatic abnormalities that are related to the interaction between soluble coagulation factors and blood cells, and the effects of hemodialysis (HD) on it, in end stage renal disease (ESRD) patients. Thirty-two ESRD patients under HD treatment and fifteen healthy controls were included in the study. Whole blood samples from the healthy and ESRD subjects were collected before and after the HD session. Evaluation of coagulation included primary and secondary hemostasis screening tests, proteins of coagulation, fibrinolytic and inhibitory system, and ADAMTS-13 activity. Phosphatidylserine (PS) exposure and intracellular reactive oxygen species (iROS) levels were also examined in red blood cells and platelets, in addition to the platelet activation marker CD62P. Platelet function analysis showed pathological values in ESRD patients despite the increased levels of activation markers (PS, CD62P, iROS). Activities of most coagulation, fibrinolytic, and inhibitory system proteins were within the normal range, but HD triggered an increase in half of them. Additionally, the increased baseline levels of ADAMTS-13 inhibitor were further augmented by the dialysis session. Finally, pathological levels of PS and iROS were measured in red blood cells in close correlation with variations in several coagulation factors and platelet characteristics. This study provides evidence for a complex coagulation phenotype in ESRD. Signs of increased bleeding risk coexisted with prothrombotic features of soluble factors and blood cells in a general hyperfibrinolytic state. Hemodialysis seems to augment the prothrombotic potential, while the persisted platelet dysfunction might counteract the increased predisposition to thrombotic events post-dialysis. The interaction of red blood cells with platelets, the thrombus, the endothelium, the soluble components of the coagulation pathways, and the contribution of extracellular vesicles on hemostasis as well as the identification of the unknown origin ADAMTS-13 inhibitor deserve further investigation in uremia.
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Liu, Max, Khalequz Zaman, and Yolanda M. Fortenberry. "Overview of the Therapeutic Potential of Aptamers Targeting Coagulation Factors." International Journal of Molecular Sciences 22, no. 8 (April 9, 2021): 3897. http://dx.doi.org/10.3390/ijms22083897.
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Aptamers are single-stranded DNA or RNA sequences that bind target molecules with high specificity and affinity. Aptamers exhibit several notable advantages over protein-based therapeutics. Aptamers are non-immunogenic, easier to synthesize and modify, and can bind targets with greater affinity. Due to these benefits, aptamers are considered a promising therapeutic candidate to treat various conditions, including hematological disorders and cancer. An active area of research involves developing aptamers to target blood coagulation factors. These aptamers have the potential to treat cardiovascular diseases, blood disorders, and cancers. Although no aptamers targeting blood coagulation factors have been approved for clinical use, several aptamers have been evaluated in clinical trials and many more have demonstrated encouraging preclinical results. This review summarized our knowledge of the aptamers targeting proteins involved in coagulation, anticoagulation, fibrinolysis, their extensive applications as therapeutics and diagnostics tools, and the challenges they face for advancing to clinical use.
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Martín-Rojas, Reyes María, Maite Chasco, Sara Casanova, Valeria Estefanía Delgado-Pinos, Gloria Perez-Rus, Patricia Duque, Milagros Sancho, Jose L. Diez-Martin, and Cristina Pascual Izquierdo. "COVID-19 Associated Coagulopathy: A Comprehensive Assessment of the Coagulation Profile in Critically and Non-Critically Ill Patients." Blood 136, Supplement 1 (November 5, 2020): 5. http://dx.doi.org/10.1182/blood-2020-138882.
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INTRODUCTION COVID-19 is associated with coagulopathy that correlates with poor prognosis. Although the underlying mechanism of COVID-19 coagulopathy remains unknown, early reports suggested that it may be a form of disseminated intravascular coagulation (DIC). However, recent studies have highlighted the potential role of endothelial cell injury in its pathogenesis. AIMS The aims of our study were to analyze the coagulation parameters of critically and non-critically ill patients with COVID-19 pneumonia admitted to our hospital, determine if coagulation factors consumption occurs, identify potential prognostic biomarkers of this new disease and explore possible underlying mechanisms of COVID-19 coagulopathy. METHODS We conducted a retrospective cohort study performed at Gregorio Marañon Hospital in Madrid, Spain. Adult patients with a diagnosis of COVID-19 hospitalized in our center were recruited, including those admitted to the ICU and to general wards. Patients were randomly selected from blood samples that arrived at our Hemostasis laboratory during April 2020. For each patient, we conducted a complete analysis of coagulation parameters, including basic coagulation tests, quantification of coagulation factors and physiological inhibitor proteins, evaluation of the fibrinolytic system and determination of von Willebrand Factor (vWF) and ADAMTS13. Laboratory data were compared with clinical data and outcomes. Data were analyzed using IBM SPSS Statistics for Mac, version 24. This study was approved by our institutional Ethics Committee and it was executed along with the international ethics recommendations for conducting research in humans following the latest revision of Declaration of Helsinki. RESULTS A total of 62 patients (31 ICU, 31 non-ICU) were analyzed. Mean age of the sample was 61.8 (SD 15.2) years and 69.4% of the patients were male. The coagulation parameters assessment demonstrated normal median PT, INR and APTT in our cohort and all coagulation factors were within normal range. Factor VIII showed an increasing trend (194.5±71.9) which could be interpreted as an acute phase reactant, and it was significantly higher in non-survivors (p=0.003). Similarly, we did not observe consumption of physiological inhibitor proteins and platelet counts were also within the normal limits, despite being slightly lower in non-survivor patients (p=0.006) (Table 1). Von Willebrand Factor (vWF) was above the normal range (median 216%, IQR 196-439, normal range 62-175%) in our cohort and higher levels of vWF-antigen (p=0.001) and vWF-activity (p=0.02) were associated with poor prognosis. Likewise, a lower ADAMTS13 activity was observed in non-survivors (p=0.008). Regarding the fibrinolytic pathway, PAI levels were above the normal range (median 52.6ng/ml, IQR 37.2-85.7, normal range 4-40ng/ml), but we found no statistically significant differences based on survival. The remaining parameters of the fibrinolytic pathway (plasminogen and alpha-2 antiplasmin) were within normal range (Table 1). ICU-patients had a poorer prognosis, with a higher rate of mortality (p=0.003). Likewise, they showed more elevated acute phase reactants (p<0.01) and higher levels of D-dimer (p=0.003) than patients hospitalized in general wards. ADAMTS13 activity was also significantly lower in this subgroup (p<0.001), as well as plasminogen levels (p=0.002) and PAI (p=0.003). Criteria of overt disseminated intravascular coagulation (DIC) as defined according to the ISTH DIC score, were met in 14.8% of ICU patients versus 0% of non-ICU patients (p=0.039) (Table 2). CONCLUSIONS COVID-19 infection is associated with coagulopathy that correlates with poor prognosis. However, coagulation factors, physiological inhibitory proteins and alpha-2-antplasmin levels were preserved in our study. Similarly, we did not observe platelets or fibrinogen consumption, which leads us to assume that COVID-19 coagulopathy is not a form of DIC. Increased vWF and decreased ADAMTS13 activity in our cohort could indicate that the underlying mechanism of this coagulopathy may reside in the endothelial cells and share a similar pathogenesis with thrombotic microangiopathy (TMA), as it has been recently suggested in some scientific reports. Disclosures No relevant conflicts of interest to declare.
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Shahramian, Khalil, Aous Abdulmajeed, Ilkka Kangasniemi, Eva Söderling, and Timo Närhi. "TiO2Coating and UV Photofunctionalization Enhance Blood Coagulation on Zirconia Surfaces." BioMed Research International 2019 (April 1, 2019): 1–9. http://dx.doi.org/10.1155/2019/8078230.
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This in vitro study was designed to evaluate the effect of sol-gel derived TiO2coating on blood coagulation, blood protein adsorption, and platelet response on zirconia surfaces. Square-shaped zirconia (n=96) (10x10x2 mm) was cut, ground, sintered, and finally cleansed ultrasonically in each of acetone and ethanol for 5 minutes. Three experimental groups (n=32) were fabricated: (a) zirconia coated with sol-gel derived TiO2, (b) zirconia coated with sol-gel derived TiO2and treated with ultraviolet (UV) irradiation for 1 hour, and (c) non-coated zirconia as control. The coatings were prepared from tetraisopropyl orthotitanate solution by dip-coating. The thrombogenicity of the specimens was evaluated using a whole blood kinetic clotting time method where the extent of blood clotting was evaluated at 10, 20, 30, 40, 50, and 60 minutes (n=4/time point, total n=24/group). Scanning electron microscope images were taken to observe platelet morphologies after 1-hour incubation with platelet-rich plasma (PRP) (n=5/group). Surface characteristics were visualized using atomic force microscopy (n=1/group). Adsorption of plasma proteins and fibronectin on each surface was studied by gel electrophoresis (n=2/group). Significant differences were observed in blood coagulation between the test groups at 20-, 30-, 40-, and 50-minute time points (p<0.005). UV treated TiO2coated specimens showed fastest blood coagulation followed by TiO2coated and non-coated specimens. Furthermore, platelets appeared at a higher activation state on coated specimens. Gel electrophoresis revealed no difference in protein adsorption among the experimental groups. In summary, TiO2coatings promoted blood coagulation, and it was further enhanced by UV treatment, which has the potential to hasten the wound healing process in vivo.
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Bodnár, T., and A. Sequeira. "Numerical Simulation of the Coagulation Dynamics of Blood." Computational and Mathematical Methods in Medicine 9, no. 2 (2008): 83–104. http://dx.doi.org/10.1080/17486700701852784.
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The process of platelet activation and blood coagulation is quite complex and not yet completely understood. Recently, a phenomenological meaningful model of blood coagulation and clot formation in flowing blood that extends existing models to integrate biochemical, physiological and rheological factors, has been developed. The aim of this paper is to present results from a computational study of a simplified version of this coupled fluid-biochemistry model. A generalized Newtonian model with shear-thinning viscosity has been adopted to describe the flow of blood. To simulate the biochemical changes and transport of various enzymes, proteins and platelets involved in the coagulation process, a set of coupled advection–diffusion–reaction equations is used. Three-dimensional numerical simulations are carried out for the whole model in a straight vessel with circular cross-section, using a finite volume semi-discretization in space, on structured grids, and a multistage scheme for time integration. Clot formation and growth are investigated in the vicinity of an injured region of the vessel wall. These are preliminary results aimed at showing the validation of the model and of the numerical code.
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Rothhut, B., C. Coméra, S. Cortial, P. Y. Haumont, K. H. Diep Le, J. C. Cavadore, J. Conard, F. Russo-Marie, and F. Lederer. "A 32 kDa lipocortin from human mononuclear cells appears to be identical with the placental inhibitor of blood coagulation." Biochemical Journal 263, no. 3 (November 1, 1989): 929–35. http://dx.doi.org/10.1042/bj2630929.
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A 32 kDa protein isolated from human mononuclear cells is a member of the lipocortin family, a new group of Ca2+-dependent lipid-binding proteins thought to be involved in the regulation of phospholipase A2, in exocytosis and in membrane-cytoskeleton interactions. Purification of this protein was based on its ability to associate with membrane phospholipids in a Ca2+-dependent manner and its capacity to inhibit purified phospholipase A2 from pig pancreas. Using immunological detection, we show that it is present in various cells involved in the inflammatory and coagulation processes. We present extensive amino acid data that strongly suggest that this protein is identical with a recently described inhibitor of blood coagulation, with endonexin II and with lipocortin V. Sequence alignment with other known proteins show a significant degree of homology with lipocortins I and II, the substrates of the epidermal-growth-factor receptor tyrosine kinase and the oncogene pp60src tyrosine kinase respectively, and with protein II. The possible physiological role of this 32 kDa lipocortin is discussed.
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Mion, B. J., and B. F. Masterson. "An immunochemical study of the binding of blood coagulation proteins to artificial surfaces." Biochemical Society Transactions 28, no. 5 (October 1, 2000): A362. http://dx.doi.org/10.1042/bst028a362a.
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Zingali, Russolina B. "INTERACTION OF SNAKE-VENOM PROTEINS WITH BLOOD COAGULATION FACTORS: MECHANISMS OF ANTICOAGULANT ACTIVITY." Toxin Reviews 26, no. 1 (January 2007): 25–46. http://dx.doi.org/10.1080/15569540600567412.
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de Boer, J. Daan, Christof J. Majoor, Cornelis van 't Veer, Elisabeth H. D. Bel, and Tom van der Poll. "Asthma and coagulation." Blood 119, no. 14 (April 5, 2012): 3236–44. http://dx.doi.org/10.1182/blood-2011-11-391532.
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Abstract Asthma is a chronic airway disease characterized by paroxysmal airflow obstruction evoked by irritative stimuli on a background of allergic lung inflammation. Currently, there is no cure for asthma, only symptomatic treatment. In recent years, our understanding of the involvement of coagulation and anticoagulant pathways, the fibrinolytic system, and platelets in the pathophysiology of asthma has increased considerably. Asthma is associated with a procoagulant state in the bronchoalveolar space, further aggravated by impaired local activities of the anticoagulant protein C system and fibrinolysis. Protease-activated receptors have been implicated as the molecular link between coagulation and allergic inflammation in asthma. This review summarizes current knowledge of the impact of the disturbed hemostatic balance in the lungs on asthma severity and manifestations and identifies new possible targets for asthma treatment.
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Nomura, Shosaku, Maiko Niki, Tohru Nisizawa, Takeshi Tamaki, and Michiomi Shimizu. "Microparticles as Biomarkers of Blood Coagulation in Cancer." Biomarkers in Cancer 7 (January 2015): BIC.S30347. http://dx.doi.org/10.4137/bic.s30347.
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Cancer is associated with hypercoagulopathy and increased risk of thrombosis. This negatively influences patient morbidity and mortality. Cancer is also frequently complicated by the development of venous thromboembolism (VTE). Tumor-derived tissue factor (TF)-bearing microparticles (MPs) are associated with VTE events in malignancy. MPs are small membrane vesicles released from many different cell types by exocytic budding of the plasma membrane in response to cellular activation or apoptosis. MPs may also be involved in clinical diseases through expression of procoagulative phospholipids. The detection of TF-expressing MPs in cancer patients may be clinically useful. In lung and breast cancer patients, MPs induce metastasis and angiogenesis and may be indicators of vascular complications. Additionally, MPs in patients with various types of cancer possess adhesion proteins and bind target cells to promoting cancer progression or metastasis. Overexpression of TF by cancer cells is closely associated with tumor progression, and shedding of TF-expressing MPs by cancer cells correlates with the genetic status of cancer. Consequently, TF-expressing MPs represent important markers to consider in the prevention of and therapy for VTE complications in cancer patients.
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Orfeo, T., S. Butenas, A. Undas, K. Brummel-Ziedins, and K. G. Mann. "Blood coagulation dynamics in haemostasis." Hämostaseologie 29, no. 01 (2009): 7–16. http://dx.doi.org/10.1055/s-0037-1616932.
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SummaryOur studies involve computational simulations, a reconstructed plasma/platelet proteome, whole blood in vitro and blood exuding from microvascular wounds. All studies indicate that in normal haemostasis, the binding of tissue factor (TF) with plasma factor (F) VIIa (extrinsic FXase complex) results in the initiation phase of the procoagulant response. This phase is negatively regulated by tissue factor pathway inhibitor (TFPI) in combination with antithrombin (AT) and the protein C (PC) pathway. The synergy between these inhibitors provides a threshold-limited reaction in which a stimulus of sufficient magnitude must be provided for continuation of the reaction. With sufficient stimulus, the FXa produced activates some prothrombin. This initial thrombin activates the procofactors and platelets required for presentation of the intrinsic FXase (FVIIIa- FIXa) and prothrombinase (FVa-FXa) complexes which drive the subsequent propagation phase; continuous downregulation of which is provided by AT and the thrombinthrombomodulin- PC complex. FXa generation during the propagation phase is largely (>90%) provided by the intrinsic FXase complex. TF is required for the initiation phase of the reaction but becomes non-essential once the propagation phase has been achieved. The propagation phase catalysts (FVIIIa-FIXa and FVa-FXa) continue to drive the reaction as blood is resupplied to the wound site by flow. Ultimately, the control of the reaction is governed by the pro- and anticoagulant dynamics and the supply of blood reactants to the site of a perforating injury. Our systems have been utilized to examine the qualities of hypothetical and novel antihaemorrhagic and anticoagulation agents and in epidemiologic studies of venous and arterial thrombosis and haemorrhagic pathology.