Academic literature on the topic 'Thrombu'
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Journal articles on the topic "Thrombu"
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Vandendries, Erik R., Justin R. Hamilton, Shaun R. Coughlin, Barbara C. Furie, and Bruce Furie. "Protease-Activator Receptor 4 Is Required for Maximal Thrombus Growth, but Not for Fibrin Generation in Thrombi after Laser Injury." Blood 104, no. 11 (November 16, 2004): 624. http://dx.doi.org/10.1182/blood.v104.11.624.624.
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Abstract The serine protease, thrombin, is necessary for the conversion of fibrinogen to fibrin and is a potent activator of platelets. Thrombin-induced platelet activation, as measured by shape change, calcium mobilization, and ATP secretion, requires the protease-activator receptor 4 (PAR4). Platelets isolated from PAR4 knock-out mice are unresponsive to thrombin, and PAR4 null mice appear to be protected from thrombosis in a ferric chloride-induced injury model of thrombosis and a thromboplastin model of pulmonary embolism. To examine further the role of thrombin-induced platelet activation in developing thrombi, we have examined the in vivo kinetics of thrombus formation in living mice lacking PAR4 using high-speed widefield digital microscopy. In this study, platelets were labeled using anti-CD41 Fab fragments conjugated to Alexa-488. Thrombi were generated by laser-induced injury of the cremaster arteriolar vessel wall, and the total fluorescent antibody accumulation was monitored and quantitated for 5 minutes after injury. In PAR4 null mice, the thrombi generated were significantly smaller with an early arrest of thrombus growth when compared to thrombi generated in wild-type mice. The maximum thrombus platelet accumulation in PAR4 null mice (median of 30 thrombi in 3 mice) was 75% less than that seen in wild-type mice (median of 33 thrombi in 4 mice)(P<0.001). The time to half-maximal and the time to maximal thrombus formation in PAR4 null mice is approximately 5.5 seconds and 16 seconds, respectively, compared to 45 seconds and 74 seconds in wild-type mice (P<0.001). The shortened time to maximal platelet accumulation appears to be secondary to an early termination of thrombus growth. Fibrin generation was monitored using Alexa-647 conjugated to an anti-fibrin antibody that does not recognize fibrinogen in mice simultaneously infused with anti-CD41 Fab conjugated to Alexa-488. No difference in total fibrin accumulation was seen during the first 4 minutes of thrombus formation in PAR4 null mice (median of 23 thrombi in 3 mice) compared to thrombi generated in wild-type mice (median of 26 thrombi in 4 mice) despite a significant decrease in platelet accumulation in PAR4 null thrombi. Most of the fibrin deposition in both wild-type and PAR4 null thrombi was observed at the vascular wall/thrombus interface. In summary, thrombin-induced platelet activation via PAR4 is required for normal thrombus growth. However, in this model of thrombosis, neither PAR4 nor maximal thrombus growth appears to be necessary for fibrin deposition. This suggests that a platelet-independent mechanism of thrombin generation may exist. Alternatively, the amount of platelet accumulation and activation in PAR4 null mice may be sufficient for normal thrombin generation and subsequent fibrin deposition.
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Mutch, N. J., L. A. Robbie, and N. A. Booth. "Human Thrombi Contain an Abundance of Active Thrombin." Thrombosis and Haemostasis 86, no. 10 (2001): 1028–34. http://dx.doi.org/10.1055/s-0037-1616529.
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SummaryThis study assessed the abundance and activity of thrombin in human thrombi, removed at autopsy or during surgery. Arterial and venous thrombus sections showed thrombin activity by in situ zymography, based on conversion of fibrinogen to fibrin. Hirudin or antibodies to thrombin abolished the activity. Thrombin activity in extracts of 40 thrombi was quantified by cleavage of fibrinogen or small peptide substrates; the results correlated well (r = 0.87, p<0.0001) with a median activity of about 4.5 IU/g of thrombus (wet weight). Activity correlated poorly with total prothrombin (median 27 μg/g) and was inversely related to antithrombin, but not to PAI-1. Zymography showed two major active bands, thrombin at 37 kDa, and a 50 kDa form that probably corresponds to meizothrombin desF1. The abundant local thrombin demonstrated here has implications for thrombus lysis and extension; incomplete lysis and exposure of active thrombin may lead to re-occlusion of vessels.
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Tucker, Erik I., Ulla M. Marzec, Andras Gruber, and Stephen R. Hanson. "Inhibition of Factor XI Decreases Thrombin Production and Prevents Vascular Occlusion in Experimental Thrombosis in Primates." Blood 110, no. 11 (November 16, 2007): 763. http://dx.doi.org/10.1182/blood.v110.11.763.763.
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Abstract Animal studies suggest that factor XI (FXI) substantially contributes to thrombus growth and stability, presumably by promoting thrombin generation upon the flow surface of thrombi. To further elucidate the role of FXI in thrombus development, we investigated the effect of FXI inhibition in baboons on the time course of thrombogenic marker generation and platelet activation, as measured in samples taken locally from the peripheral blood intraluminal boundary layer (IBL) that superfused forming experimental thrombi. We also tested whether FXI inhibition would reduce thrombus stability under flow and/or prevent thrombotic vessel occlusion. Thrombogenesis was initiated by placement of collagen coated clinical vascular grafts (polytetrafluoroethylene, 4 mm i.d. and 2 mm i.d.) as extension segments within a chronic arteriovenous shunt. Blood flow was controlled at 100 mL/min, producing wall shear rates of 265 sec−1 and 2120 sec−1 within the 4 mm and 2 mm devices, respectively. Deposition of 111In-labelled platelets onto collagen was measured by gamma camera imaging for 60 min. Fibrin accumulation was measured using 125I-labelled fibrinogen. Template bleeding times were used to assess hemostatic impairment. FXI was blocked by a single bolus i.v. injection of an anti-human FXI monoclonal antibody (aXIMab, 2 mg/kg), which neutralized more than 95% of circulating FXI-related procoagulant activity for at least 7 days. aXIMab administration reduced platelet and fibrin deposition by 39–59% and 83–89%, respectively (N=3), in the 4 mm grafts vs. untreated controls (N=8). IBL thrombin/antithrombin III (TAT) and β-thromboglobulin (βTG) levels were reduced by aXIMab treatment at all time points after initiation of thrombus, up to 38-fold and 7-fold respectively. In control experiments, local TAT and βTG levels peaked at about 30 min and then decreased, correlating with the time course of platelet deposition. Inhibition of FXI significantly reduced thrombus stability under high shear, enhancing distal thrombo-embolization with large reductions in thrombus volume. In contrast, significant thromboembolization was not seen in control experiments. While 2 mm grafts consistently occluded within 30 min in control studies, thrombo-occlusion was prevented by aXIMab treatment over the 1 hour study interval. Local D-dimer levels were not affected by FXI blockade, nor were bleeding times prolonged by the antibody. These findings demonstrate that inhibition of FXI can dramatically attenuate thrombin production at sites of forming thrombus, thereby reducing platelet activation, fibrin formation and vascular occlusion without compromising primary hemostasis as assessed by measurements of bleeding time. The lack of D-dimer elevation over the study interval did not, however, support a mechanism of enhanced thrombolysis during FXI inhibition in primates. Since inhibition of FXI with aXIMab prevented graft occlusion without apparent compromise of hemostasis in primates, this strategy may prove an attractive one for antithrombotic applications in man.
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Dubois, Christophe, Laurence Panicot-Dubois, Glenn Merrill-Skoloff, Bruce Furie, and Barbara C. Furie. "Glycoprotein VI–dependent and –independent pathways of thrombus formation in vivo." Blood 107, no. 10 (May 15, 2006): 3902–6. http://dx.doi.org/10.1182/blood-2005-09-3687.
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The role of the collagen receptor glycoprotein VI (GPVI) in arteriolar thrombus formation was studied in FcRγ-null mice (FcRγ–/–) lacking platelet surface GPVI. Thrombi were induced with severe or mild FeCl3 injury. Collagen exposure was significantly delayed and diminished in mild compared with severe FeCl3 injury. Times to initial thrombus formation and vessel occlusion were delayed in FcRγ–/– compared with wild-type mice after severe injury. Platelet accumulation in wild-type mice was decreased after mild compared with severe injury. However, there was little difference between platelet accumulation after severe or mild injury in FcRγ–/–. These data indicate a significant role for GPVI in FeCl3-induced thrombus formation. Pretreatment of wild-type mice with lepirudin further impaired mild FeCl3-induced thrombus formation, demonstrating a role for thrombin. Laser-induced thrombus formation in wild-type and FcRγ–/– was comparable. Collagen exposure to circulating blood was undetectable after laser injury. Normalized for thrombus size, thrombus-associated tissue factor was 5-fold higher in laser-induced thrombi than in severe FeCl3-induced thrombi. Thus, platelet activation by thrombin appears to be more important after laser injury than platelet activation by GPVI-collagen. It may thus be important when considering targets for antithrombotic therapy to use multiple animal models with diverse pathways to thrombus formation.
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Robbie, Linda, Susan Berry, Bruce Bennett, Nicola Mutch, Elaine Moir, and Nuala Booth. "Localization and Identification of Thrombin and Plasminogen Activator Activities in Model Human Thrombi by in situ Zymography." Thrombosis and Haemostasis 88, no. 12 (2002): 996–1002. http://dx.doi.org/10.1055/s-0037-1613346.
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SummaryHuman thrombi vary in their susceptibility to lysis and this is clinically important. Several potential contributory factors were examined in this study by using model thrombi, created under flow; these provide a robust, reproducible and easily-manipulated system. Here we identify the plasminogen activators (PA) active in model thrombi of known age and define the cellular and plasma contribution to activity in different areas. The cell-rich head of model thrombi had strong thrombin and PA activity, with coagulant activity also at the tail. Thrombin activity decreased as model thrombi were aged. PA activity in the thrombus head also decreased on ageing of thrombi but activity emerged around the thrombi, including the tail. Activity in the head of fresh model thrombi was primarily due to uPA, with some contribution from tPA. Experiments with thrombi prepared from platelet-rich plasma and added leucocytes showed that uPA activity at the head of fresh thrombi was derived from PMN. Older thrombi had tPA activity around the tail of the thrombus; this activity occurred in the absence of cells. This study highlights the importance of PMN-derived uPA activity in the lysis of fresh thrombi, with activity originating in the leucocyte-rich head. It also shows that thrombi are dynamic structures in which fibrin can be repeatedly laid down and lysed, observations that are relevant to therapeutic lysis and potential rethrombosis.
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Tucker, Erik I., Ulla M. Marzec, Tara C. White, Sawan Hurst, Sandra Rugonyi, Owen J. T. McCarty, David Gailani, András Gruber, and Stephen R. Hanson. "Prevention of vascular graft occlusion and thrombus-associated thrombin generation by inhibition of factor XI." Blood 113, no. 4 (January 22, 2009): 936–44. http://dx.doi.org/10.1182/blood-2008-06-163675.
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Abstract The protease thrombin is required for normal hemostasis and pathologic thrombogenesis. Since the mechanism of coagulation factor XI (FXI)–dependent thrombus growth remains unclear, we investigated the contribution of FXI to thrombus formation in a primate thrombosis model. Pretreatment of baboons with a novel anti–human FXI monoclonal antibody (aXIMab; 2 mg/kg) inhibited plasma FXI by at least 99% for 10 days, and suppressed thrombin-antithrombin (TAT) complex and β-thromboglobulin (βTG) formation measured immediately downstream from thrombi forming within collagen-coated vascular grafts. FXI inhibition with aXIMab limited platelet and fibrin deposition in 4-mm diameter grafts without an apparent increase in D-dimer release from thrombi, and prevented the occlusion of 2-mm diameter grafts without affecting template bleeding times. In comparison, pretreatment with aspirin (32 mg/kg) prolonged bleeding times but failed to prevent graft occlusion, supporting the concept that FXI blockade may offer therapeutic advantages over other antithrombotic agents in terms of bleeding complications. In whole blood, aXIMab prevented fibrin formation in a collagen-coated flow chamber, independent of factor XII and factor VII. These data suggest that endogenous FXI contributes to arterial thrombus propagation through a striking amplification of thrombin generation at the thrombus luminal surface.
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Wysokinski, Waldemar, Robert McBane, James H. Chesebro, and Whyte G. Owen. "Reversibility of Platelet Thrombosis In Vivo." Thrombosis and Haemostasis 76, no. 06 (1996): 1108–13. http://dx.doi.org/10.1055/s-0038-1650714.
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SummaryReversibility in vivo of acute platelet thrombosis in response to specific anticoagulants is analyzed with thrombi that develop in segments (1 cm) of porcine carotid arteries externally crushed with a hemostat. Most thrombi fill the lumens of the injured segments (ca. 1 cm × 3 mm, 1 × w) within 30 min and comprise masses of platelets interpenetrated with neutrophil-lined seepage channels of blood. Continuous quantitative assay of thrombus mass is provided by a gamma detector placed over the injured segments to collect counts from 111In-labeled platelets. Thrombi established 30 min after injury, otherwise stable for 6 h, clear during 30-60 min of continuous infusion of either hirudin, tick anticoagulant or activated porcine protein C, or intermittent activation of endogenous protein C with a latent thrombin reagent. Anticoagulant dose-dependence of thrombus clearance is established for hirudin between 0.01 and 1.0 mg/kg/min. Thrombi become progressively refractory to hirudin between 0.5 and 6 h after injury. Neither heparin nor low-molecular-weight heparin in full (clinical) anticoagulant doses yield significant dethrombosis. It is concluded that, within time limits, controlled thrombin generation in platelet thrombi maintains platelet cohesion without catalyzing irreversible platelet aggregation or clotting of fibrinogen.
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Dubois, Christophe, Laurence Panicot-Dubois, Justin F. Gainor, Barbara C. Furie, and Bruce Furie. "Thrombin-Dependent Platelet Activation Is VWF-Independent during Thrombus Formation In Vivo." Blood 108, no. 11 (November 16, 2006): 1510. http://dx.doi.org/10.1182/blood.v108.11.1510.1510.
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Abstract Adhesion to and activation of platelets at an injured vessel wall are critical events in the formation of a thrombus. Calcium mobilization is one marker of platelet activation. Of different agonists capable of activating platelets in vitro, thrombin, collagen and vWF have been described to induce calcium mobilization, leading to the formation of aggregates. Using high speed digital multichannel intravital microscopy, we characterized calcium mobilization during platelet activation and thrombus formation in genetically modified mice. The kinetics of platelet activation and accumulation after laser-induced injury in cremaster muscle arterioles of living mice were analyzed. In wild type mice, platelets adhered and accumulated rapidly at the site of laser-induced injury. Thrombi increased in size, reached a maximum size at 90–120 sec, decreased in size and then stabilized within 3 to 4 min post-injury. In vWF−/− mice, the kinetics of platelet accumulation followed the same pattern as in wild type mice. However, a significant albeit modest reduction in the size of each thrombus was observed in these genetically deficient mice in comparison with wild type mice. By ranking the thrombi by size, we observed that 40% of the thrombi formed in vWF−/− mice were present in the quadrant containing the smallest thrombi versus 18% for the wild type mice. Only 8% of the thrombi formed in vWF−/− mice were distributed in the quadrant containing the largest thrombi versus 32% for the wild type mice. In wild type mice treated with lepirudin, a specific inhibitor of thrombin activity, a small early accumulation of platelets was observed at about 16 sec whereas in untreated wild type mice this early accumulation is often obscured by subsequent thrombin-mediated platelet accumulation and activation. However, at the time of maximal thrombus size in wild-type mice, platelet accumulation in wild type mice was more than ten-fold greater than in wild type mice treated with lepirudin. The kinetics of platelet accumulation were similar in FcRγ−/− mice lacking GPVI, GPVI-depleted mice and wild type mice. Furthermore, depletion of GPVI from the platelet surface of vWF−/− mice or platelets of wild type mice treated with lepirudin did not alter the kinetics of platelet accumulation in those mice. By monitoring calcium mobilization per platelet engaged in the growing thrombus, we observed that elevated calcium levels in each platelet were similar in FcRγ−/−, GPVI depleted, vWF−/− and wild type mice. However in wild type mice treated with lepirudin, platelet calcium mobilization was almost completely inhibited in comparison with those observed in wild type mice. Our results indicate that thrombin is the major agonist leading to platelet activation after laser-induced injury. Collagen, as previously reported (Dubois, Blood.2006;107:3902) does not play a role in platelet thrombus formation after laser injury and, based on data reported here, does not play a role in platelet activation in this model. vWF is important for the growth of the platelet thrombus but is not required for initial platelet accumulation or platelet activation in vivo in this thrombosis model. The platelet agonist or ligand responsible for initial early platelet accumulation after laser-induced injury is unknown, and does not require GPVI, thrombin or vWF.
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Brill-Edwards, Patrick, Joanne Van Ryn-McKenna, Lu Cai, Frederick A. Ofosu, and Michael R. Buchanan. "Prevention of Thrombus Growth by Antithrombin III-Dependent and Two Direct Thrombin Inhibitors in Rabbits: Implications for Antithrombotic Therapy." Thrombosis and Haemostasis 68, no. 04 (1992): 424–27. http://dx.doi.org/10.1055/s-0038-1646290.
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SummaryWe compared the abilities of heparin and two direct thrombin inhibitors to prevent fibrin accretion onto pre-existing thrombi in rabbits. Inhibition of thrombus growth was measured as the ability of each test compound to inhibit the accretion of 125I-fibrin onto thrombi pre-formed in jugular veins of rabbits. When administered as a continuous infusion, the two direct (i. e. antithrombin III-independent) thrombin inhibitors, r-hirudin and a tripeptide, Ac(D)-Phe-Pro-bor-Arg (P-8714) inhibited fibrin accretion as effectively as heparin, but did so in doses which generated little systemic anticoagulation, as compared to the marked anticoagulation associated with the heparin effect. However, both r-hirudin and P-8714 were more effective when they were administered as a single bolus injection than as a continuous infusion. Under the former conditions, there was only a transient systemic anticoagulant effect. We conclude that direct or antithrombin III-independent thrombin inhibitors are more effective than heparin in preventing thrombus growth. The limited effect of heparin is likely due to fibrin impairing the ability of heparin/antithrombin III to inactivate thrombin.
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Chou, Janet, Nigel Mackman, Glenn Merrill-Skoloff, Brian Pedersen, Barbara C. Furie, and Bruce Furie. "Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation." Blood 104, no. 10 (November 15, 2004): 3190–97. http://dx.doi.org/10.1182/blood-2004-03-0935.
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Abstract Tissue factor (TF) is expressed on nonvascular cells and cells within the vessel wall and circulates in blood associated with microparticles. Although blood-borne TF accumulates into the developing thrombus during thrombus formation, the contribution of blood-borne TF and vessel wall TF to thrombin generation in vivo following vessel injury is unknown. To determine the source and role of blood-borne microparticle TF, we studied arterial thrombus formation in a living mouse using intravital microscopy. Platelet, TF, and fibrin accumulation in the developing thrombus was compared in wild-type and low TF mice. Compared to wild-type mice, low TF mice formed very small platelet thrombi lacking TF or fibrin. Wild-type and low TF mice received transplants of bone marrow from wild-type and low TF mice. Arterial thrombi in low TF bone marrow/wild-type chimeric mice had decreased size and decreased TF and fibrin levels. Arterial thrombi in wild-type bone marrow/low TF chimeric mice showed decreased platelet thrombus size but normal TF and fibrin levels. This demonstrates that blood-borne TF associated with hematopoietic cell-derived microparticles contributes to thrombus propagation.
Dissertations / Theses on the topic "Thrombu"
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Mutch, Nicola J. "Thrombin activity in human thrombi and the vessel wall." Thesis, University of Aberdeen, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340809.
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Moir, Elaine. "The pro- and anti-fibrinolytic properties of human leucocytes." Thesis, University of Aberdeen, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340602.
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Petersen, Helen J. "Streptococcus-induced thrombus formation." Thesis, University of Bristol, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.541609.
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Machi, Paolo. "Evaluation expérimentale des propriétés mécaniques et de l'efficacité d'enlèvement des thrombus des stent retrievers." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT263/document.
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Un certain nombre d'essais cliniques contrôlés, randomisés et publiés récemment en littérature a démontré que la thrombectomie mécanique, offerte aux patients présentant un AVC ischémique aigu, est liée à une meilleure évolution clinique en comparaison au traitement standard de fibrinolyse intraveineuse. Les stents retriever ont été reconnus dans ces essais comme les dispositifs les plus efficaces pour la thrombectomie intracrânienne. Actuellement, toutes les industries produisant des dispositifs neuro-interventionnels lancent sur le marché un nombre croissant de stents retriever. Chaque nouveau dispositif proposé est censé avoir une particularité permettant de meilleures performances par rapport aux dispositifs déjà disponibles sur le marché. Néanmoins, aucune étude clinique n’a démontré, jusqu'à présent, la supériorité en termes de résultats anatomiques et cliniques d'un stent retriever donné. En outre, le mécanisme d'interaction entre les stents retriever et le thrombus n'a pas été évalué jusqu'ici de façon exhaustive. Dans la présente étude, nous avons analysé expérimentalement les performances de tous les stents retriever disponibles sur le marché français jusqu'à juin 2015. Le but de cette étude était d'identifier toutes les caractéristiques des dispositifs fonctionnels à la capture du thrombus. Chaque dispositif a été évalué par des tests mécaniques et fonctionnels : les tests mécaniques ont été effectués afin d'étudier la force radiale des dispositifs. L'objectif était d'évaluer la force radiale exercée par le stent dans deux conditions spécifiques : lors du déploiement et pendant le retrait.Les tests fonctionnels ont visé à évaluer visuellement la capacité du stent à rester en apposition sur la paroi des vaisseaux et à maintenir le thrombus à l'intérieur de ses mailles au cours du retrait. Nous avons évalué l'interaction des dispositifs avec thrombus de taille et de caractéristiques différentes que nous avons générées en utilisant du sang humain afin d'obtenir deux types de caillot : un souple « de type rouge » composé par tous les éléments du sang et un dur « de type blanc» qui a été principalement composé de plasma riche en plaquettes. Ces essais ont été effectués en utilisant un modèle vasculaire rigide reproduisant la circulation cérébrale antérieure. Deux neuro-interventionnels ayant une expérience dans les procédures de thrombectomie ont effectué les tests fonctionnels. Chaque expérience a été filmée et deux auteurs par la suite ont effectué une analyse visuelle des résultats.Les essais mécaniques ont montré un comportement différent en termes de variation de pression radiale au cours du retrait pour chaque stent. Une pression radiale constante pendant le retrait est liée à une cohésion constante sur la paroi artérielle pendant le retrait, avec un taux plus important de retrait du caillot. Tous les stents retriever glissent sur le caillot blanc de grande taille (diamètre>6 mm) ayant un très bas taux d’efficacité en termes de retraitA number of randomized controlled trials recently appeared in literature demonstrated that early mechanical thrombectomy offered to patients presenting with acute ischemic stroke is related to improved functional outcome in comparison to standard care intravenous fibrinolysis. Stent retrievers have been recognized in these trials as the most effective devices for intracranial thrombectomy. Currently, all industries producing neuro-interventional devices are launching into the market an increasing number of stent-based retriever tools. Each new device proposed for clinical use is supposed to have peculiar features allowing better performances in comparison to devices already available for clinical practice. Nevertheless, none clinical study has demonstrated so far the superiority, in terms of anatomical and clinical results, of a given stent retriever device. Furthermore, the mechanism of interaction between stent retrievers and thrombi has not exhaustively evaluated so far. In the present study we experimentally analyzed performances of all stent retrievers available into the French market up to Juin 2015. The aim of this study was to identify any device feature that was functional to the thrombus removal.Stent retrievers were evaluated by mechanical and functional test: mechanical tests were performed in order to investigate devices radial force, the aim was to evaluate the radial force exerted by the stent in two specific conditions: upon deployment and during the retrieval.Functional tests were aimed to visually evaluate the stent retriever’s ability in remaining in close apposition to the vessels wall and to maintain the thrombus engaged within its struts during the retrieval. We evaluated the interaction of the devices with thrombi of different features and sizes that we generated using human blood in order to obtain two types of clot: one softer “red type” that was composed by all elements of the whole blood and one stiffer “white type” that was mainly composed by platelet-rich plasma. Such tests were conducted using a rigid 3D printed vascular model reproducing the brain anterior circulation. Two neuro-interventionalists with experience in thrombectomy procedures performed functional tests, each experiment was filmed and two authors thereafter conducted visual analysis of the results.Mechanical tests showed different behavior in terms of radial pressure variation during retrieval for each stent. Constant radial pressure during retrieval was related to constant cohesion over the vessel wall during retrieval and higher rate of clot removal efficacy. All stent retrievers slide over the clot failing in clot removal when interact with white large thrombi (diameter>6 mm)
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Ramaiola, Ilaria. "Thrombus composition in acute coronary syndrome." Doctoral thesis, Universitat Pompeu Fabra, 2015. http://hdl.handle.net/10803/456681.
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Atherothrombosis and, specifically intracoronary thrombosis is a major cause of acute coronary syndromes (ACS) and consequently of morbidity and mortality throughout the world. While management of acute ST-elevation myocardial infarction (STEMI) has dramatically improved over the last years, there is still a need to find thrombosis-related biomarkers for an early identification of ischemic processes and a better stratification of patients that have suffered an ACS. In fact, the ischemia time, defined as the time from the onset of symptoms to reperfusion, has been recently suggested as the “New Gold Standard for STEMI-Care”. This thesis mainly focuses on the protein composition of the occluding coronary thrombus, occurring both in the native coronary arteries and in the commonly implanted coronary stents. The study based on the proteomic analysis of coronary thrombi, obtained after percutaneous coronary intervention (PCI), has provided consistent evidence of the dynamic composition of the coronary thrombi in relation with the time of ischemia, and has resulted in the identification of novel biomarkers of potential use to be translated to the clinical practice. Furthermore, the comparison of native and in-stent-thrombosis has allowed the identification of proteins that might serve as interesting therapeutic targets to prevent thrombosis in patients who undergo PCI with stent-implantation.La enfermedad aterotrombotica y concretamente la trombosis intracoronaria es la mayor causa de los síndromes coronarios agudos (SCA), y consecuentemente de morbilidad y mortalidad en el mundo. El manejo de los pacientes con infarto agudo de miocardio con elevación del segmento ST ha mejorado considerablemente en los últimos años, a pesar de esto sigue siendo necesario encontrar biomarcadores para la detección temprana de los procesos isquémicos y que permitan una estratificación más eficiente de los pacientes que han sufrido un evento isquémico agudo. De hecho, el tiempo de isquemia, definido como el tiempo entre el inicio del dolor y la revascularización, ha sido recientemente definido como el parámetro fundamental en el tratamiento de los pacientes con STEMI. Este trabajo de tesis está enfocado a elucidar la composición proteica de los trombos coronarios oclusivos que se forman tanto en las arterias coronarias nativas como en aquellas con stent. El estudio se basa en el análisis proteómico de trombos coronarios en relación al tiempo de isquemia, con la finalidad de encontrar nuevos biomarcadores para trasladar a la práctica clínica. Además, la comparación entre trombos nativos y trombos desarrollados sobre el stent permite la identificación de proteínas diferenciales que podrían ser futuras dianas terapéuticas para prevenir la formación del trombo en pacientes sometidos a angioplastia coronaria transluminal percutánea (ACTP) con implantación de un stent coronario.
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Bowker, Timothy J. "A computational model for thrombus prediction." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558527.
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The haemostatic system stops the loss of blood, thereby maintaining the integrity of the circulatory network. Whilst haemostasis is necessary for survival, thrombosis - haemostasis in the wrong place - is the most common cause of mortality in the West. The presence of a thrombus is governed by the triad of endothelial injury, blood constitution and flow. The central protein involved in this process is thrombin which is formed through a reaction network known as the coagulation cascade. Cerebral saccular aneurysms are balloon like dilations of the cerebral vasculature that are estimated to be present in 2-6% of the population. The currently preferred treatment method for such aneurysms is the deliberate initiation of thrombus formation (leading to occlusion) through the placement of platinum coils within the aneurysm. An emerging alternative is the use of a stent which is deployed across the aneurysm neck, reducing the rate at which flow enters the aneurysm, leading again to the controlled formation of a thrombus. A comprehensive model of thrombus formation within cerebral aneurysms should simulate the reduction to flow as the thrombus grows within the aneurysm. The model must capture the spatial and temporal regulators of thrombus formation - incorporating both biological and mechanical factors. This first part of this thesis examines the sensitivity of flow conditions within cerebral aneurysms to changes in boundary conditions (simulated exercise) and geometrical changes (stent placement). The main contribution of this thesis is the development of frameworks which enable examination of thrombus formation. First, an idealised arteriole is used to examine the impact of flow upon two approaches to computational modelling of thrombin generation. The second framework uses the Level Set technique to track the position of a thrombus surface within a patient specific aneurysmal geometry.
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Glossop, Paul. "Thrombin inhibition." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244533.
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Levade, Marie. "Mécanismes moléculaires de la production et des fonctions plaquettaires : rôle de Vps34 et impact des inhibiteurs ciblés de kinases." Thesis, Toulouse 3, 2017. http://www.theses.fr/2017TOU30036.
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Les plaquettes sanguines jouent un rôle essentiel dans le maintien de l'intégrité des vaisseaux sanguins. En cas de brèche vasculaire, elles conduisent à la formation d'un clou hémostatique via des étapes successives d'adhésion, sécrétion et agrégation finement régulées et préviennent alors un saignement excessif. Les plaquettes jouent également un rôle critique dans les pathologies thrombotiques comme l'athérothrombose, ce qui en fait des cibles pharmacologiques majeures dans ces situations. Au cours de ma thèse, deux axes de recherche ont été abordés : (i) l'étude du rôle de la PI3-kinase de classe III (Vps34) dans la formation et l'activation des plaquettes et (ii) l'étude de l'impact de nouvelles drogues ciblant les kinases en thérapie anti-cancéreuse sur les fonctions plaquettaires et l'hémostase. Dans un premier temps, je me suis concentrée sur la caractérisation du rôle de Vps34 et de son produit lipidique, le phosphatidylinositol 3 monophosphate (PtdIns3P), dans la physiologie plaquettaire à l'aide d'un modèle de souris présentant une délétion de Vps34 spécifiquement dans la lignée mégacaryocyte/plaquette (PF4-Cre/Vps34lox/lox). Nous avons observé une microthrombopénie modérée associée à un défaut de migration des mégacaryocytes ainsi que des anomalies morphologiques des granules de sécrétion. Ce phénotype apparaît lié à une diminution de taux de PtdIns3P associé à un trafic vésiculaire perturbé. De plus, nous avons mis en évidence une altération des fonctions prothrombotiques des plaquettes, ex vivo en conditions de flux mais aussi in vivo en conférant aux souris une protection contre la thrombose induite à la carotide par lésion au chlorure ferrique. La contribution de Vps34 dans les mécanismes d'activation plaquettaire, indépendamment de son rôle dans le mégacaryocyte, a été montrée ex vivo via l'utilisation de nouveaux inhibiteurs spécifiques de Vps34 (SAR405 et INH1) récemment développés pour une application en oncologie, notamment pour réduire la résistance de certains cancers aux chimiothérapies. Dans un second temps, je me suis intéressée à l'impact des nouvelles thérapies ciblées anticancéreuses sur les plaquettes afin de comprendre la majoration du risque hémorragique associée à ces molécules. Nous avons étudié l'effet de l'ibrutinib, un inhibiteur des tyrosine-kinases de la famille BTK activées en aval des PI3-kinases de classe I, utilisé en clinique dans le traitement des hémopathies lymphoïdes B (lymphomes et leucémie lymphoïde chronique). L'exploration des fonctions plaquettaires au sein d'une cohorte de patients du service d'hématologie du CHU-Toulouse a permis de corréler les signes hémorragiques de certains patients traités par ibrutinib avec un défaut de signalisation plaquettaire en aval des récepteurs GPVI et GPIb, se traduisant par une diminution de l'agrégation au collagène et au CRP et par un défaut d'adhésion sur matrice de facteur von Willebrand en conditions de flux. En conclusion, mes travaux de thèse (i) apportent de nouvelles données fondamentales sur la participation de Vps34 dans les mécanismes de production et d'activation plaquettaires et (ii) ont permis de proposer des recommandations quant à l'utilisation clinique des nouvelles thérapies ciblées anti-cancéreusesBlood platelets play an essential role in the maintenance of vascular integrity. They prevent excessive blood loss after vessel injury by orchestrating haemostatic clot formation through successive steps of adhesion, secretion and aggregation. Platelets are also major pharmacologic targets as they participate in thrombotic pathologies such as atherosclerosis. My thesis work was focused on two axis: (i) the role of class III PI3-kinase (Vps34) in platelet formation and activation and (ii) the impact of new anticancer drugs targeting kinases on platelet functions and haemostasis. First, I studied the role of Vps34 and its lipid product, phosphatidylinositol 3 monophosphate (PtdIns3P), in platelet physiology using a unique mouse model of Vps34 deletion specifically in megakaryocyte lineage (PF4-Cre/Vps34lox/lox). We observed a moderate microthrombocytopenia associated to a defect in megakaryocyte migration and morphologic abnormalities in secretion granules. This phenotype is linked to a decrease in PtdIns3P level associated with defective vesicular trafficking. Moreover, PF4-Cre/Vps34lox/lox mice exhibit altered prothrombotic functions, ex vivo in shear conditions and in vivo by conferring a protection against ferric chloride-induced carotid thrombosis. A role for Vps34 in platelet activation, independently from its role in megakaryocyte, was shown ex vivo using two specific Vps34 inhibitors (SAR405 and INH1) recently developed to reduce autophagy-mediated resistance to chemotherapy. Secondly, I assessed the impact of new targeted drugs used in cancer therapy on platelets in order to understand the increased bleeding risk associated to these molecules. We studied the effect of ibrutinib, a specific inhibitor of BTK family tyrosine kinases recently approved for the treatment of B malignancies (mantle cell lymphoma, chronic lymphocytic leukemia). By exploring platelet functions of ibrutinib-treated patients treated from Hematology department of Toulouse, we correlated bleeding symptoms to a defective platelet signaling downstream GPVI and GPIb receptors as shown by a strongly reduced platelet aggregation in response to collagen and CRP and by a defect in platelet adhesion on von Willebrand matrix under flow conditions. In conclusion, my thesis work (i) brings fundamental insights about Vps34 contribution in mechanisms of platelet production and functions and (ii) allows recommendations about clinical use of new targeted molecules in cancer therapy
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Cardillo, Giulia. "Fluid Dynamic Modeling of Biological Fluids : From the Cerebrospinal Fluid to Blood Thrombosis." Thesis, Institut polytechnique de Paris, 2020. http://www.theses.fr/2020IPPAX110.
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Dans cette thèse, trois modèles mathématiques ont été proposés, avec l’objectif de modéliser autant d’aspects complexes de la biomédecine, dans lesquels la dynamique des fluides du système joue un rôle fondamental: i) les interactions fluide-structure entre la pulsatilité du liquide céphalo-rachidien et la moelle épinière (modélisation analytique); ii) dispersion efficace d’un médicament dans l’espace sous-arachnoïdien (modélisation numérique); et iii) la formation et l’évolution d’un thrombus au sein du système cardiovasculaire (modélisation numérique).Le liquide céphalorachidien est un fluide aqueux qui entoure le cerveau et la moelle épinière afin de les protéger. Une connaissance détaillée de la circulation du liquide céphalorachidien et de son interaction avec les tissus peut être importante dans l’étude de la pathogenèse de maladies neurologiques graves, telles que la syringomyélie, un trouble qui implique la formation de cavités remplies de liquide (seringues) dans la moelle épinière.Par ailleurs, dans certains cas, des analgésiques - ainsi que des médicaments pour le traitement de maladies graves telles que les tumeurs et les infections du liquide céphalorachidien - doivent être administrés directement dans le liquide céphalorachidien. L’importance de connaître et de décrire l’écoulement du liquide céphalorachidien, ses interactions avec les tissus environnants et les phénomènes de transport qui y sont liés devient claire. Dans ce contexte, nous avons proposé: un modèle capable de décrire les interactions du liquide céphalo-rachidien avec la moelle épinière, considérant cela, pour la première fois, comme un milieu poreux imprégné de différents fluides (sang capillaire et veineux et liquide céphalo-rachidien); et un modèle capable d’évaluer le transport d’un médicament dans l’espace sousarachnoïdien, une cavité annulaire remplie de liquide céphalo-rachidien qui entoure la moelle épinière.Avec le troisième modèle proposé, nous entrons dans le système cardiovasculaire.Dans le monde entière, les maladies cardiovasculaires sont la cause principale de mortalité. Parmi ceux-ci, nous trouvons la thrombose, une condition qui implique la formation d’un caillot à l’intérieur d’un vaisseau sanguin, qui peut causer sa occlusion. À cet égard, un modèle numérique a été développé qui étudie la formation et l’évolution des thrombus, en considérant simultanément les aspects chimico-biomécaniques et dynamiques des fluides du problème. Dans le modèle proposé pour la première fois, l'importance du rôle joué par les gradients de contrainte de cisaillement dans le processus de thrombogenèse est pris en compte.Les modèles sélectionnés ont fourni des résultats intéressants. Tout d’abord, l’étude des interactions fluide-structure entre le liquide céphalo-rachidien et la moelle épinière a mis en évidence es conditions pouvant induire l’apparition de la syringomyélie. Il a été observé comment la déviation des valeurs physiologiques du module d’Young de la moelle épinière, les pressions capillaires dans l’interface moelle-espace sousarachnoïdien et la perméabilité des compartiments capillaire et veineux, conduisent à la formation de seringues.Le modèle de calcul pour l’évaluation de la dispersion pharmacologique dans l’espace sousarachnoïdien a permis une estimation quantitatif de la diffusivité effective du médicament, une quantité qui peut aider à l’optimisation des protocoles d’injections intrathécales.Le modèle de thrombogenèse a fourni un instrument capable d’étudier quantitativement l’évolution des dépôts de plaquettes dans la circulation sanguine. En particulier, les résultats ont fourni des informations importantes sur la nécessité de considérer le rôle de l’activation mécanique et de l’agrégation des plaquettes aux côtés de la substance chimiqueIn the present thesis, three mathematical models are described. Three different biomedical issues, where fluid dynamical aspects are of paramount importance, are modeled: i) Fluid-structure interactions between cerebro-spinal fluid pulsatility and the spinal cord (analytical modeling); ii) Enhanced dispersion of a drug in the subarachnoid space (numerical modeling); and iii) Thrombus formation and evolution in the cardiovascular system (numerical modeling).The cerebrospinal fluid (CSF) is a liquid that surrounds and protects the brain and the spinal cord. Insights into the functioning of cerebrospinal fluid are expected to reveal the pathogenesis of severe neurological diseases, such as syringomyelia that involves the formation of fluid-filled cavities (syrinxes) in the spinal cord.Furthermore, in some cases, analgesic drugs -- as well drugs for treatments of serious diseases such as cancers and cerebrospinal fluid infections -- need to be delivered directly into the cerebrospinal fluid. This underscores the importance of knowing and describing cerebrospinal fluid flow, its interactions with the surrounding tissues and the transport phenomena related to it. In this framework, we have proposed: a model that describes the interactions of the cerebrospinal fluid with the spinal cord that is considered, for the first time, as a porous medium permeated by different fluids (capillary and venous blood and cerebrospinal fluid); and a model that evaluates drug transport within the cerebrospinal fluid-filled space around the spinal cord --namely the subarachnoid space--.The third model deals with the cardiovascular system. Cardiovascular diseases are the leading cause of death worldwide, among these diseases, thrombosis is a condition that involves the formation of a blood clot inside a blood vessel. A computational model that studies thrombus formation and evolution is developed, considering the chemical, bio-mechanical and fluid dynamical aspects of the problem in the same computational framework. In this model, the primary novelty is the introduction of the role of shear micro-gradients into the process of thrombogenesis.The developed models have provided several outcomes. First, the study of the fluid-structure interactions between cerebro-spinal fluid and the spinal cord has shed light on scenarios that may induce the occurrence of Syringomyelia. It was seen how the deviation from the physiological values of the Young modulus of the spinal cord, the capillary pressures at the SC-SAS interface and the permeability of blood networks can lead to syrinx formation.The computational model of the drug dispersion has allowed to quantitatively estimate the drug effective diffusivity, a feature that can aid the tuning of intrathecal delivery protocols.The comprehensive thrombus formation model has provided a quantification tool of the thrombotic deposition evolution in a blood vessel. In particular, the results have given insight into the importance of considering both mechanical and chemical activation and aggregation of platelets
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Chalayer, Emilie. "Myélome multiple et maladie thrombo-embolique veineuse : aspects épidémiologiques, économiques, physiopathologiques et pharmacologiques." Thesis, Saint-Etienne, 2015. http://www.theses.fr/2015STET007T/document.
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Comme dans tout cancer, l'association entre myélome multiple et maladie thrombo-embolique veineuse est bien établie. Son incidence au cours du myélome est en moyenne de 10 à 20%. Elle semble plus élevée en cas de myélome de novo et lors de l’utilisation de traitements immunomodulateurs comme le thalidomide. Pourtant, la part de surcroît du risque de thrombose dû à ce traitement n’est pas encore très bien définie. Tout d’abord, nous avons réalisé un bilan de ces pathologies afin de délimiter le champ d’étude grâce à une revue de la littérature. Nous avons ensuite évalué l’incidence de la maladie thrombo-embolique veineuse, identifié les facteurs de risque thrombotique et évalué le classement en groupe de risque des patients présentant un myélome et traités par immunomodulateur grâce à une étude observationnelle, multicentrique, prospective, de la prise en charge des myélomes par les hématologues en France. Par la suite, nous avons réalisé l’analyse médico-économique du seul essai randomisé réalisé à ce jour sur la thrombophylaxie chez les malades présentant un myélome multiple traités par thalidomide en première ligne. Cette étude montre un gain de qualité de vie associé à des économies majeures lors de la prévention de la thrombose par aspirine plutôt que par héparine. Enfin nous avons réalisé 2 études médicales utilisant la génération de thrombine, test biologique de recherche. La première a été effectuée afin d’essayer de prédire les patients qui vont présenter une thrombose. La deuxième a pour but de rechercher l’existence d’une résistance à l’héparine aux doses habituelles utilisées dans cette pathologieThe association between multiple myeloma and venous thromboembolic disease is well established. This incidence in myeloma is on average from 10 to 20%. It appears to be higher in newly diagnosed myeloma and immunomodulatory drugs such as thalidomide might significantly increase the risk. However, the risk of thrombosis due to these treatments is not yet well defined. First, we performed a review of these diseases in order to delimit the field of this study through a literature review. Then, we evaluated the incidence of venous thromboembolic disease in patients with myeloma and treated with immunomodulatory, identified the thrombotic risk factors and evaluated the thrombotic risk assessment based on the physicians choice, through an observational, multicenter, prospective French study. Moreover, we performed the medico-economic analysis of the only randomized trial conducted to date on the thrombophylaxis in patients with multiple myeloma treated with thalidomide in the first line of chemotherapy. This analysis showed a gain in quality of life associated with significant cost savings in the prevention of thrombosis by aspirin rather than heparin. Finally we performed two medical studies using thrombin generation test, a global assay that measures the overall tendency of a plasma sample to form thrombin. The first study was conducted to predict patients who will have thrombosis. The second is performed to know if a heparin resistance with the usual doses in this pathology, exists
Books on the topic "Thrombu"
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Maragoudakis, Michael E., and Nikos E. Tsopanoglou, eds. Thrombin. New York, NY: Springer New York, 2009. http://dx.doi.org/10.1007/978-0-387-09637-7.
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Berliner, Lawrence J., ed. Thrombin. Boston, MA: Springer US, 1992. http://dx.doi.org/10.1007/978-1-4615-3296-5.
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Tew, David. Throsby revisited. Wymondhanm, Melton Mowbray, Leicestershire: Witmehá Press, 1989.
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Heart throbs. London: Octopus Books, 1985.
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Heart throbs. London: Xpresso, 1991.
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J, Berliner Lawrence, ed. Thrombin: Structure and function. New York: Plenum Press, 1992.
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Wang, Lemin. The Origin and Onset of Thrombus Disease. Singapore: Springer Singapore, 2018. http://dx.doi.org/10.1007/978-981-10-7344-1.
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A, Greer I., ed. Thrombo-embolic disease in obstetrics and gynaecology. London: Baillière Tindall, 1997.
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Summers, Andy. Throb. London: Sidgwick & Jackson, 1986.
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Berliner, Lawrence J. Thrombin: Structure and Function. Boston, MA: Springer US, 1992.
Find full textBook chapters on the topic "Thrombu"
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Bährle-Rapp, Marina. "Thrombus (Plur.: Thromben)." In Springer Lexikon Kosmetik und Körperpflege, 555. Berlin, Heidelberg: Springer Berlin Heidelberg, 2007. http://dx.doi.org/10.1007/978-3-540-71095-0_10524.
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Ruan, Lei, Le Zhang, and Cuntai Zhang. "Thrombus." In Encyclopedia of Gerontology and Population Aging, 1–9. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-319-69892-2_1062-1.
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Ruan, Lei, Le Zhang, and Cuntai Zhang. "Thrombus." In Encyclopedia of Gerontology and Population Aging, 5148–57. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-22009-9_1062.
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Cera*, Enrico Di, and Andras Gruber. "Thrombin: Structure, Functions, and Regulation." In Thrombin, 1–18. New York, NY: Springer New York, 2008. http://dx.doi.org/10.1007/978-0-387-09637-7_1.
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Salah, Zaidoun, Sorina Grisaru-Granovsky, Myriam Maoz, Beatrice Uziely, Irit Cohen, Hagit Turm, Tamar Peretz, and Rachel Bar-Shavit*. "The Role of Thrombin and its Receptors in Epithelial Malignancies: Lessons from a Transgenic Mouse Model and Transcriptional Regulation." In Thrombin, 173–88. New York, NY: Springer New York, 2008. http://dx.doi.org/10.1007/978-0-387-09637-7_10.
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Petralia*, Gloria A., and Ajay K. Kakkar. "Anti-thrombotic Therapy in Cancer Patients." In Thrombin, 189–203. New York, NY: Springer New York, 2008. http://dx.doi.org/10.1007/978-0-387-09637-7_11.
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Chen*, Cailin, Bruce E. Maryanoff*, and Patricia Andrade-Gordon. "Thrombin Receptor Modulators: Medicinal Chemistry, Biological Evaluation, and Clinical Application." In Thrombin, 205–36. New York, NY: Springer New York, 2008. http://dx.doi.org/10.1007/978-0-387-09637-7_12.
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Mousa, Shaker A. "Novel Anticoagulant Therapy: Principle and Practice." In Thrombin, 237–57. New York, NY: Springer New York, 2008. http://dx.doi.org/10.1007/978-0-387-09637-7_13.
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Ramachandran, Rithwik, Mahmoud El-Daly, Mahmoud Saifeddine, and Morley D. Hollenberg*. "Thrombin: To PAR or Not to PAR, and the Regulation of Inflammation." In Thrombin, 19–46. New York, NY: Springer New York, 2008. http://dx.doi.org/10.1007/978-0-387-09637-7_2.
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Trejo, JoAnn. "Regulation of Thrombin Receptor Signaling." In Thrombin, 47–61. New York, NY: Springer New York, 2008. http://dx.doi.org/10.1007/978-0-387-09637-7_3.
Full textConference papers on the topic "Thrombu"
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Schmidt, B., M. R. Buchanan, F. Ofosu, L. A. Brooker, M. Andrew, and McMaster Univ. "ANTITHROMBOTIC PROPERTIES OF HEPARIN IN A NEONATAL MODEL OF THROMBIN INDUCED VENOUS STASIS THROMBOSIS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643608.
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Anecdotal clinical experience suggests that more heparin is required in newborn infants that in adult patients to effectively treat thrombotic disease. We compared the ability of heparin to inhibit thrombus formation induced by a pathological bolus of thrombin and stasis in newborn piglets and 3 week old pigs. The coagulation system of the newborn piglet closely resembles that of the human neonate Including low antithrombin III (AT-III) activity (0.5U/ml). By 3 weeks, adult porcine values for coagulation factors and inhibitors are reached, while blood volume/kg body weight still approximates that of the newborn piglet. Piglets and pigs were pretreated with saline, 10 or 25U/kg heparin (n ≥16/group/dose. Following an injection of 100U/kg thrombin, systemic 125I-fibrinogen consumption and local 125I-fibrinogen incorporation into jugular venous stasis thrombi were measured. Peak heparin levels were identical In both age groups (Anti-factor Xa assay and protamine sulphate titration). Heparin was less effective in preventing thrombus formation in piglets than in pigs (Table). Heparin was also less effective in preventing systemic neonatal 125I-fibrinogen consumption (p<0.0001 at both heparin doses).Raising AT-III levels to adult values significantly improved the antithrombotic properties of heparin in neonatal piglets. Thrombus formation was completely abolished in 19 or 22 piglets who received a combination of human or porcine AT-III concentrate and 25U/kg heparin. Raising the heparin dose to 50U/kg had the same effect. We conclude that the efficacy of heparin in neutralizing thrombin is decreased in newborn piglets. Treatment with AT-III concentrate overcomes this relative heparin resistance, and may help reduce high heparin doses otherwise required in neonatal thrombotic disease.
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Slaboch, Constance L., and Timothy Ovaert. "Mechanical Characterization and Simulation of Murine Thrombi." In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53190.
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Deep vein thrombosis (DVT) is the formation of a thrombus, or blood clot, in one of the extremities, often in the vein of a leg. Approximately 2 million incidences of DVT occur annually. Roughly 300,000 people die due to the development of a pulmonary embolism (PE), which occurs when the thrombus from a DVT relocates to the pulmonary artery. Abdominal aortic aneurysm (AAA) is another life-threatening disease involving thrombi, resulting in 15,000 deaths annually. Together, these diseases impact over 2.5 million people each year. The effects of mechanical properties on thrombi dissociation and aortic rupture are not well characterized, and this lack of knowledge has hampered significant treatment and management of many blood-related diseases, as well as the development of optimal drug therapies. Determining these mechanical properties (i.e., elastic modulus and viscosity) is valuable information, as it can be used as inputs to simulations of thrombi disorders to more accurately determine thrombus dissociation or aortic rupture. The goal of this research is to determine the mechanical properties of murine (rat) thrombi under physiologic conditions via nanoindentation, for use as inputs data to numerical flow simulations.
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Palabrica, Theresa M., Barbara C. Furie, Marvin A. Konatam, Barbara Brockway, Mart Aronovitz, and Bruce Furie. "IMAGING OF THROMBI USING ANTI-PADGEM ANTIBODIES SPECIFIC FOR ACTIVATED PLATELETS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643955.
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PADGEM protein is a platelet-specific alpha grannie membrane protein that is translocated to the plasma membrane during platelet activation and secretion. Monoclonal EC4 and polyclonal anti-PADGEM antibodies are specific for PADGEM on activated platelets. Because PADGEM is internal in unstimulated platelets* these antibodies do not bind to resting platelets. Since activated platelets are concentrated in thrombi, we used radiolabeled anti-PADGEM antibodies to image thrombi in baboons.In vitro: Dacron graft material incubated with thrombin-activated platelet-rich plasma and 131I-KC4, 131I-anti-PADGEM, 131I-nonimmune IgG or 131-BSA bound 95%, 70%, 9% and 1% of the radiolabel, respectively, after exhaustive washing.In vivo: Imaging experiments were carried out in baboons with an external Dacron shunt between the femoral artery and vein. Gamma camera images following 123I-anti-PADGEM infusion (1.0 mCi; 300 μg) demonstrated intense uptake in the thrombus induced by the Dacron vascular graft within 10 minutes. The graft:blood pool activity ratio was 33:1. Control experiments with 123I-nonimmune IgG showed minimal uptake. 123I-anti-PADGEM cleared the circulating blood pool with an initial half-disappearance time of 2-6 minutes. The primary routes of metabolism were hepatic uptake, dehalogenation and urinary excretion of free iodine. There was no evidence that the anti-PADGEM antibodies had any adverse effects on the normal processes of hemostasis in any of these experiments.Anti-PADGEM antibodies, both monoclonal and polyclonal, are directed against activated platelets in thrombi or in areas of tissue injury; they do not bind to resting platelets in the circulation. Radioimmunoscintigraphy with these agents provides a novel approach to the noninvasive detection and localization of thrombi in vivo, with potential application to human disease. Furthermore, linkage of these antibodies to fibrinolytic enzymes offers a strategy for the specific lysis of thrombi in vivo.
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Yano, K., and T. Yamaguchi. "Computational Mechanical Simulation of the Aggregation and Dissociation of Platelets Mediated by von Willebrand Factor." In ASME 2002 International Mechanical Engineering Congress and Exposition. ASMEDC, 2002. http://dx.doi.org/10.1115/imece2002-32575.
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Platelets play an important role in blood coagulation, particularly in the formation of primary thrombi. The aggregation of platelets, which initiates primary thrombi formation, is thought to be mediated by the von Willebrand factor (vWF). The vWF is a long-chain macromolecule that exists in a soluble form in the blood flow and an insoluble form in the vessel wall. Figure 1 schematically shows normal (a) and pathological (b) thrombus formation processees. In both cases, platelets adhere to the injured vessel wall and then form a thrombus in cooperation with the fibrin network, red cells, and other blood constituents. The vWF plays a more important role in pathological thrombosis formation than in the normal hemostatic process, due to its ability to sense and react to hemodynamic stress.
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Slaboch, Constance L., and Timothy C. Ovaert. "Mechano-Rheological Properties of the Murine Thrombus Determined via Nanoindentation and Finite Element Modeling." In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-206520.
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Deep vein thrombosis (DVT) is the formation of a thrombus, or blood clot, in one of the extremities, often in the vein of a leg. Approximately 2 million incidences of DVT occur annually [1]. Roughly 300,000 people die due to the development of a pulmonary embolism (PE), which occurs when the thrombus from a DVT relocates to the pulmonary artery. Abdominal aortic aneurysm (AAA) is another life-threatening disease involving thrombi, resulting in 15,000 deaths annually. Increased life expectancy raises significant concern for AAA, as it generally affects people age 55 and older. Together, these diseases impinge over 2.5 million people each year. Determining the mechanical properties of thrombi, which can be platelet- and/or fiber-rich, and understanding how they dissociate or fail mechanically under fluid flow conditions, can help diagnose these diseases at an earlier stage in their progression, thereby providing time to initiate treatments. In addition, increased knowledge of thrombi properties can lead to the development of preventative drug therapies. Both of these outcomes have the potential to decrease the number of deaths from the aforementioned diseases.
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Coller, B. S., J. D. Folts, S. R. Smith, and L. E. Scudder. "ABOLITION OF IN VIVO PLATELET THROMBUS FORMATION WITH MONOCLONAL ANTIBODIES TO THE PLATELET GPIIb/IIla RECEPTOR: CORRELATION WITH PLATELET AGGREGATION AND BLEEDING TIME." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643703.
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We previously reported that 0.8 mg/kgof the F(ab’)2 fragment of antibody 7E3, directed at theplatelet GPIIb/IIIa receptor, can abolish periodic platelet thrombus formation on partially stenosed carotid arteries in monkeys (Mnks). The present study was designed to: 1) test another antibody to GPIIb/IIIa (10E5), 2)find the minimum effective dose, and 3) correlate this effect with changesin the template bleeding time (BT) and platelet aggregation (PA). Periodicplatelet thrombi were established in the carotid arteries of 7 anesthetized Mnks after mechanical stenosis (∽70%) and intimal damage. 4 Mnks were treated with 7E3. Mnks 1 and 2 were given 0.2 mg/kg, and this dose: abolished thrombus formation and prevented its return in response to epinephrine infusion and increased intimal damage; abolished PA in response to ADP (10 μM); and increased the BT from 8.5 to 16 min and from 5 to 11 min. Mnk 3 was given 0.1 mg/kg, and this dose abolished the thrombi, inhibited PA by ∽41% and increased the BT only to 10 minfrom 8 min. Mnk 4 was givenincremental doses of 7E3. After 0.1 mg/kg, thrombi were reduced but not abolished, PA was minimally inhibited and the BTwas unchanged (7.5 vs 8 min pre). Afteranother 0.1 mg/kg, thrombi were abolished but could be partially restoredwith extreme provocation, PA was abolished and BT remained 7.5min. Afteranother 0.2 mg/kg, thrombicould not berestored, PA was abolished and the BTincreased to 21 min. After a final0.2mg/kg, the BT increased to 33 min. 3 Mnks were treated with 10E5. Mnk1received 0.4 mg/kg: thrombi and PA werebothabolished, and the BT increased from 5.5 to 14.5 min.Mnk 2 received 0.2mg/kg: thrombi and PA were again abolished while the BT increased to8.5from4.5 min. Mnk 3 received 0.1 mg/kg, and this abolished thrombus formation,butinhibitedPA by only ∽50%and increasedthe BT minimally (7.5 to 8.5 min). Increasedoozing from the neckwounds wasonly observed in animals with significant BT prolongations.We conclude that ∽0.1-0.2 mg/kg of eitherantibody can abolish in vivo thrombusformation, and that it is not necessary to abolish PA or cause marked prolongation ofthe BT in order toabolishthrombus formation in this model.
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Miyazaki, Hisako, Hao Liu, and Takami Yamaguchi. "Computational Mechanical Analysis of the Platelets Behavior in the Blood Flow Using Discrete Element Method." In ASME 2000 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2000. http://dx.doi.org/10.1115/imece2000-2534.
Full textAbstract:
Abstract Platelets play an important role in blood coagulation, particularly in the formation of primary thrombi. It is thought that the aggregation of platelets, which initiates primary thrombi formation, is mediated by a macromolecule called von Willebrand Factor (vWF). vWF is a long chain macromolecule that exists in the blood flow as a soluble form and in the vessel wall as an insoluble form. Figure 1 schematically shows normal (a) and pathological (b) thrombus formation processes as illustrated by Ikeda (1998) In both cases, platelets adhere to the injured vessel wall and then form a thrombus in cooperation with the fibrin network, red cells, and other blood constituents. vWF is thought to play a more important role in pathological thrombosis formation than in the normal hemostatic process, particularly due to its ability to react to hemodynamic stress.
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Rehse, K., U. Lukens, S. Leibring, V. Schein, and A. Kesselhut. "ANTITHROMBOTIC OLIGOAMINES." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643439.
Full textAbstract:
We have found that oligoamines of the general formula R2−3X(R=-(CH2)m-NH-(CH2)n-Y) in which X and Y may be aliphatic, alicyc-lic, aromatic or even heterocyclic moieties are a new class of compounds which exhibit platelet aggregation inhibiting and anticoagulant activities in vitro and have antithrombotic properties in vivo. The compound RE 1492 (N,N’,N1’-Tris-4-phenylbutylbenzene-1,3,5-trimethanamine) is chosen as example to demonstrate these effects. In PRP the following IC50 of RE 1492 (inductor in brackets) were measured: 3 ¼mol/L (Collagen), 1 ¼mol/L (ADP, 2ndphase), 7.5 μmol/L (ADP, lstphase), 2,5 μmol/L (A 23187, 2ndphase), 7,5 μmol/L (Ionophor A 23187, lstphase), 30 ¼mol/L (Thrombin). The inhibition of the aggregation Induced by ADP could as well be demonstrated in whole blood. The formation of fibrin was inhibited as shown by the prolongation of the thromboplastin time (Quick) and the partial thromboplastin time (PTT) the first being more sensitive (25% of normal at 50 ymol/L) than the latter (25% of normal at 100 ymol/L). The reason was the inhibition of coagulation factors in the following order: VII (25% of normal at 12.5 ¼mol/L) >WErwnr/IX (25 ¼mol/L) »X (200 μmol/L). The thrombin time remains normal. The antithrombotic properties of RE 1492 were investigated in an in vivo thrombosis model. The formation of platelet thrombi in mesenteric arterioles and venoles of rats (diameterM5 ym) was induced by a laser beam. In controls 1,76±1,14 (SD) shots (50 msec, 50 mW) on the arterioles were necessary for thrombus formation. Twenty minutes after i.v. application of RE 1492 this number rose to 3,18±2,08 (3 mg/kg, p ≤ 0,01, X2-test) and 4,59±1,93 (10 mg/kg, p ≤ 0,01) in arterioles. In venoles of the control animals 1,29±0,45 shots were necessary for thrombus formation. This number rose to 2,11±1,62 (p ≤ 0,05) after 3 mg/kg and 3,28±2,03 (p0,01) after 10 mg/kg. As the number of shots applied was limited to five an average shot number of 5± SD would indicate that no thrombus formation takes place at all. As RE 1492 does neither influence the metabolic pattern of arachidonic acid in platelets nor the activity of phosphodiesterase or adenylatcyclase it is supposed that the oligoamines exert their effects by interaction with phospholipids (PL) resulting in a “membrane stabilization” in platelets and inhibition of PL dependent coagulation factors during fibrin formation.
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AlMomani, T., H. S. Udaykumar, J. Marshall, and K. B. Chandran. "Dynamic Simulation of Red Blood Cells/Platelet Interaction in Arteriolar Blood Flow." In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-175290.
Full textAbstract:
Hemodynamic forces have been proposed as a major factor in thrombosis (thrombus formation) in the human cardiovascular system [1]. It has been suggested that platelet activation, aggregation and adhesion to the surface of the implants result in the formation of the mural thrombi [2]. Red blood cells (RBCs) are thought to play a significant role in the dynamics and the activation of the platelets and hence thrombus formation in the human arterial system. Previous experimental works indicate that RBCs cause platelets to migrate and move toward the vessel walls [3]. Thrombus formation has also been shown to increase as the hematocrit (Hct) increases [4]. In order to simulate the platelet dynamics requires the computational analysis of the transport and collision of the formed elements under physiological flow. In the present study, a two-dimensional (2D) simulation of the RBC/platelet dynamics in the arterioles is described.
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Wiese, B., and K. Hess. "When a Thrombus Is Not a Thrombus: To Anticoagulate or Not to Anticoagulate." In American Thoracic Society 2020 International Conference, May 15-20, 2020 - Philadelphia, PA. American Thoracic Society, 2020. http://dx.doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7311.
Full textReports on the topic "Thrombu"
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Zhou, Xiao, and Guangcheng Luo. Does tumor thrombus level affect prognosis of nephrectomy？. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, December 2021. http://dx.doi.org/10.37766/inplasy2021.12.0064.
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Mitrophanov, Alexander Y., Frits R. Rosendaal, and Jaques Reifman. Computational Analysis of Intersubject Variability and Thrombin Generation in Dilutional Coagulopathy. Fort Belvoir, VA: Defense Technical Information Center, November 2012. http://dx.doi.org/10.21236/ada568041.
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Zhou, Xiao, and Guangcheng Luo. Whether the consistency of tumor thrombus has prognostic significance in patients with renal cell carcinoma—a meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, February 2022. http://dx.doi.org/10.37766/inplasy2022.2.0015.
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Fu, Yu-Fei, Yuan-Shun Xu, and Fu-Kang Yuan. Transcatheter arterial chemoembolization with portal vein radioactive seeds insertion for hepatocellular carcinoma with portal vein tumor thrombus: a meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, February 2021. http://dx.doi.org/10.37766/inplasy2021.2.0036.
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Song, Ruirui, Fang Liu, Xiaojing Shi, Hongmei Gao, Jun Chen, Xuefeng Guo, and Jian Huang. Diagnostic accuracy of left atrial/left atrial appendage thrombus in patients with atrial fibrillation：a systematic review and network meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, December 2022. http://dx.doi.org/10.37766/inplasy2022.12.0041.
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Wang, Kai-feng. Efficacy of prostaglandina E1 for the treatment of patients with thrombo-occlusive vasculitis: a protocol of systematic review and meta-analysis. INPLASY - International Platform of Registered Systematic Review Protocols, April 2020. http://dx.doi.org/10.37766/inplasy2020.4.0081.
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Winkelstein, Beth A. Salmon Thrombin as a Treatment to Attenuate Acute Pain and Promote Tissue Healing by Modulating Local Inflammation. Fort Belvoir, VA: Defense Technical Information Center, December 2012. http://dx.doi.org/10.21236/ada579110.
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Wei, Dongmei, Yang Sun, and Hankang Hen. Effects of Baduanjin exercise on cardiac rehabilitation after percutaneous coronary intervention: A protocol for systematic review and meta-analysis of randomized controlled trials. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, April 2022. http://dx.doi.org/10.37766/inplasy2022.4.0080.
Full textAbstract:
Review question / Objective: Can Baduanjin exercise improve the cardiac rehabilitation of patients with coronary artery disease after percutaneous coronary artery surgery? Condition being studied: Coronary heart disease (CHD), also known as coronary artery disease (CAD), is the single most common cause of death globally, with 7.4 million deaths in 2013, accounting for one-third of all deaths (WHO 2014). PCI has been shown to be effective in reducing mortality in patients with CHD. During follow-up, it has been shown that the benefits of PCI can be offset by the significant risks of coronary spasm, endothelial cell injury, recurrent ischemia, and even restenosis or thrombus. Numerous guidelines endorse the necessity for cardiac rehabilitation (CR), which is recommended for patients with chronic stable angina, acute coronary syndrome and for patients following PCI. Baduanjin have been widely practised in China for centuries, and as they are considered to be low risk interventions, their use for the prevention of cardiovascular disease is now becoming more widespread. The ability of Baduanjin to promote clinically meaningful influences in patients with CHD after PCI, however, still remains unclear.