Academic literature on the topic 'Platelet dynamics/thrombosis'
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Journal articles on the topic "Platelet dynamics/thrombosis"
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Filipovic, N., M. Kojic, and A. Tsuda. "Modelling thrombosis using dissipative particle dynamics method." Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 366, no. 1879 (July 2008): 3265–79. http://dx.doi.org/10.1098/rsta.2008.0097.
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Aim . Arterial occlusion is a leading cause of cardiovascular disease. The main mechanism causing vessel occlusion is thrombus formation, which may be initiated by the activation of platelets. The focus of this study is on the mechanical aspects of platelet-mediated thrombosis which includes the motion, collision, adhesion and aggregation of activated platelets in the blood. A review of the existing continuum-based models is given. A mechanical model of platelet accumulation onto the vessel wall is developed using the dissipative particle dynamics (DPD) method in which the blood (i.e. colloidal-composed medium) is treated as a group of mesoscale particles interacting through conservative, dissipative, attractive and random forces. Methods . Colloidal fluid components (plasma and platelets) are discretized by mesoscopic (micrometre-size) particles that move according to Newton's law. The size of each mesoscopic particle is small enough to allow tracking of each constituent of the colloidal fluid, but significantly larger than the size of atoms such that, in contrast to the molecular dynamics approach, detailed atomic level analysis is not required. Results . To test this model, we simulated the deposition of platelets onto the wall of an expanded tube and compared our computed results with the experimental data of Karino et al . ( Miscrovasc. Res. 17 , 238–269, 1977). By matching our simulations to the experimental results, the platelet aggregation/adhesion binding force (characterized by an effective spring constant) was determined and found to be within a physiologically reasonable range. Conclusion . Our results suggest that the DPD method offers a promising new approach to the modelling of platelet-mediated thrombosis. The DPD model includes interaction forces between platelets both when they are in the resting state (non-activated) and when they are activated, and therefore it can be extended to the analysis of kinetics of binding and other phenomena relevant to thrombosis.
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Kim, Dongjune A., Katrina J. Ashworth, Jorge Di Paola, and David N. Ku. "Platelet α-granules are required for occlusive high-shear-rate thrombosis." Blood Advances 4, no. 14 (July 22, 2020): 3258–67. http://dx.doi.org/10.1182/bloodadvances.2020002117.
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Abstract von Willebrand factor (VWF) is essential for the induction of arterial thrombosis. In this study, we investigated the critical role of platelet VWF in occlusive thrombosis formation at high shear in mice that do not express platelet VWF (Nbeal2−/−). Using in silico modeling, in vitro high-shear microfluidics, and an in vivo Folts model of arterial thrombosis we reproduced the platelet dynamics that occur under pathological flow in a stenosed vessel. Computational fluid dynamics (CFDs) simulated local hemodynamics in a stenosis based on arterial geometries. The model predicted shear rates, time course of platelet adhesion, and time to occlusion. These predictions were validated in vitro and in vivo. Occlusive thrombosis developed in wild-type control mice that had normal levels of plasma VWF and platelet VWF in vitro and in vivo. Occlusive thrombosis did not form in the Nbeal2−/− mice that had normal plasma VWF and an absence of platelet VWF. Occlusive thrombosis was corrected in Nbeal2−/− microfluidic assays by the addition of exogenous normal platelets with VWF. Combining model and experimental data, we demonstrated the necessary requirement of platelet VWF in α-granules in forming an occlusive thrombus under high shear. These results could inspire new pharmacological targets specific to pathological conditions and prevent arterial thrombosis.
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Stritt, Simon, Inga Birkholz, Sarah Beck, Simona Sorrentino, K. Tanuj Sapra, Julien Viaud, Johannes Heck, et al. "Profilin 1–mediated cytoskeletal rearrangements regulate integrin function in mouse platelets." Blood Advances 2, no. 9 (May 8, 2018): 1040–45. http://dx.doi.org/10.1182/bloodadvances.2017014001.
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Key Points Profilin 1–mediated cytoskeletal dynamics regulate platelet β1- and β3-integrin function and turnover. Profilin 1 deficiency in platelets impairs hemostasis and results in a marked protection from arterial thrombosis.
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Yangfan Zhou, Mengjiao Hu, Xiaoyan Chen, Shuai Wang, Jingke Li, Lina Sa, Li Li, Jiaqi Huang, Hongqiang Cheng, and Hu Hu. "Migfilin supports hemostasis and thrombosis through regulating platelet αIIbβ3 outside-in signaling." Haematologica 105, no. 11 (December 26, 2019): 2608–18. http://dx.doi.org/10.3324/haematol.2019.232488.
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Elucidating the regulation mechanism of integrin αIIbβ3 is key to understand platelet biology and thrombotic diseases. Previous in vitro studies have implicated a role of migfilin in the support of platelet αIIbβ3 activation, however, contribution of migfilin to thrombosis and hemostasis in vivo and a detailed mechanism of migfilin in platelets are not known. In this study, with migfilin deletion (migfilin-/-) mice, we report that migfilin is a pivotal positive regulator of hemostasis and thrombosis. Migfilin-/- mice showed a nearly doubled tail-bleeding time and a prolonged occlusion time in Fecl3-induced mesenteric arteriolar thrombosis. Migfilin deficiency impedes platelet thrombi formation on collagen surface and impairs platelet aggregation and dense-granule secretion. Supported by characteristic functional readings and phosphorylation status of distinctive signaling molecules in the bidirectional signaling processes of αIIbβ3, the functional defects of migfilin-/- platelets appear to be mechanistically associated with a compromised outside-in signaling, rather than inside-out signaling. A synthesized cell-permeable migfilin peptide harboring filamin A binding sequence rescued the defective function and phosphorylation of signaling molecules of migfilin-/- platelets. Finally, migfilin does not influence the binding of filamin A and β3 subunit of αIIbβ3 in resting platelets, but hampers the re-association of filamin A and β3 during the conduct of outside-in signaling, suggesting that migfilin functions through regulating the interaction dynamics of αIIbβ3 and filamin A in platelets. Our study enhances the current understanding of platelet integrin αIIbβ3-mediated outside-in signaling and proves that migfilin is an important regulator for platelet activation, hemostasis and thrombosis.
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Belyaev, Aleksey V. "Computer modelling of initial platelet adhesion during microvascular thrombosis." Russian Journal of Numerical Analysis and Mathematical Modelling 34, no. 5 (October 25, 2019): 241–51. http://dx.doi.org/10.1515/rnam-2019-0020.
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Abstract Hemostasis is one of the most important protective mechanisms that functions to maintain vascular integrity and prevent bleeding. In arterial and microvascular circulation, where the near-wall shear stress is relatively high, the hemostatic response begins with aggregation of platelets on the injured endothelium or collagen. Regulation of hemostasis and thrombosis is immensely complex, as it depends on the blood cell adhesion and fluid dynamics. A possible regulatory mechanism relies on the coil-stretch transitions in a plasma protein — von Willebrand factor — that serves as a ligand to platelet adhesive membrane receptors. In this work, the initial stages of thrombus growth are studied using a 3D computer model that explicitly accounts for the shear-dependent vWf conformation.
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Grande Gutiérrez, Noelia, Mark Alber, Andrew M. Kahn, Jane C. Burns, Mathew Mathew, Brian W. McCrindle, and Alison L. Marsden. "Computational modeling of blood component transport related to coronary artery thrombosis in Kawasaki disease." PLOS Computational Biology 17, no. 9 (September 7, 2021): e1009331. http://dx.doi.org/10.1371/journal.pcbi.1009331.
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Coronary artery thrombosis is the major risk associated with Kawasaki disease (KD). Long-term management of KD patients with persistent aneurysms requires a thrombotic risk assessment and clinical decisions regarding the administration of anticoagulation therapy. Computational fluid dynamics has demonstrated that abnormal KD coronary artery hemodynamics can be associated with thrombosis. However, the underlying mechanisms of clot formation are not yet fully understood. Here we present a new model incorporating data from patient-specific simulated velocity fields to track platelet activation and accumulation. We use a system of Reaction-Advection-Diffusion equations solved with a stabilized finite element method to describe the evolution of non-activated platelets and activated platelet concentrations [AP], local concentrations of adenosine diphosphate (ADP) and poly-phosphate (PolyP). The activation of platelets is modeled as a function of shear-rate exposure and local concentration of agonists. We compared the distribution of activated platelets in a healthy coronary case and six cases with coronary artery aneurysms caused by KD, including three with confirmed thrombosis. Results show spatial correlation between regions of higher concentration of activated platelets and the reported location of the clot, suggesting predictive capabilities of this model towards identifying regions at high risk for thrombosis. Also, the concentration levels of ADP and PolyP in cases with confirmed thrombosis are higher than the reported critical values associated with platelet aggregation (ADP) and activation of the intrinsic coagulation pathway (PolyP). These findings suggest the potential initiation of a coagulation pathway even in the absence of an extrinsic factor. Finally, computational simulations show that in regions of flow stagnation, biochemical activation, as a result of local agonist concentration, is dominant. Identifying the leading factors to a pro-coagulant environment in each case—mechanical or biochemical—could help define improved strategies for thrombosis prevention tailored for each patient.
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Dubois, Christophe, Laurence Panicot-Dubois, Barbara C. Furie, and Bruce Furie. "Dynamics of Calcium Mobilization in Platelets during Thrombus Formation in a Living Mouse." Blood 106, no. 11 (November 16, 2005): 649. http://dx.doi.org/10.1182/blood.v106.11.649.649.
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Abstract Platelet accumulation at sites of vascular injury arrests bleeding but also plays a critical role in the pathogenesis of thrombosis, leading to ischemia in myocardial infarction or stroke. Intracellular calcium mobilization in platelets is a critical step in the activation of platelets and formation of the platelet thrombus. Here we show the relationship of the dynamics of intracellular calcium mobilization with platelet accumulation into the developing thrombus in a living mouse. Following injection of 100 x 106 fura-2 loaded platelets into a living mouse we used high speed intravital multi-channel digital fluorescence microscopy to monitor calcium status in circulating and thrombus-bound platelets during thrombus development. One population of platelets binds transiently to the developing thrombus but does not mobilize calcium. The mean duration of platelet-thrombus interaction for these platelets is 11 sec. Another population of platelets undergoes calcium mobilization after binding to the developing thrombus. The time interval from attachment to calcium mobilization for individual platelets varied from 1.0 to 12 sec, with a median of 3.5 sec. More than 90% of platelets that undergo calcium mobilization do so with in 5 sec of attachment. The calcium mobilization in the thrombus bound platelets is reversible. About two thirds of the platelets return rapidly to the basal Ca2+ state while the remaining thrombus bound platelets maintain an elevated Ca2+ level for an extended period. The mean duration of platelet-thrombus interaction is 35 sec with a range of 1.5 sec to 284 sec (median duration 39.5 sec) as calculated from multiple independent observations of single platelets. In each platelet studied, only one calcium peak is detected per platelet. There is a close correlation between the duration of calcium mobilization in an individual platelet and the time that the platelet remains attached to the developing thrombus, suggesting a relationship of calcium-dependent events and platelet-thrombus affinity. A population of platelets binds to the thrombus, mobilizes calcium and remains associated with the thrombus. Using widefield deconvolution techniques to obtain planar images and increased numbers of dye-loaded platelets, individual platelets could be observed undergoing sustained calcium elevation within the thrombus. As the platelet thrombus reaches maximal size at about 120 sec, calcium mobilization continues in the stable core of the thrombus for several minutes, then decreases. These studies describe thrombus formation in a living animal under conditions in which the endothelium and vessel wall, blood cells and plasma components, and flowing blood are preserved in the absence of anticoagulants. Our results indicate that stable platelet thrombus formation is dependent upon durable calcium mobilization, and that intracellular calcium regulates thrombus development and maturation in vivo.
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de Vrij, Edwin L., Hjalmar R. Bouma, Maaike Goris, Ulrike Weerman, Anne P. de Groot, Jeroen Kuipers, Ben N. G. Giepmans, and Robert H. Henning. "Reversible thrombocytopenia during hibernation originates from storage and release of platelets in liver sinusoids." Journal of Comparative Physiology B 191, no. 3 (March 4, 2021): 603–15. http://dx.doi.org/10.1007/s00360-021-01351-3.
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AbstractImmobility is a risk factor for thrombosis due to low blood flow, which may result in activation of the coagulation system, recruitment of platelets and clot formation. Nevertheless, hibernating animals—who endure lengthy periods of immobility—do not show signs of thrombosis throughout or after hibernation. One of the adaptations of hemostasis in hibernators consists of a rapidly reversible reduction of the number of circulating platelets during torpor, i.e., the hibernation phase with reduction of metabolic rate, low blood flow and immobility. It is unknown whether these platelet dynamics in hibernating hamsters originate from storage and release, as suggested for ground squirrel, or from breakdown and de novo synthesis. A reduction in detaching forces due to low blood flow can induce reversible adhesion of platelets to the vessel wall, which is called margination. Here, we hypothesized that storage-and-release by margination to the vessel wall induces reversible thrombocytopenia in torpor. Therefore, we transfused labeled platelets in hibernating Syrian hamster (Mesocricetus auratus) and platelets were analyzed using flow cytometry and electron microscopy. The half-life of labeled platelets was extended from 20 to 30 h in hibernating animals compared to non-hibernating control hamsters. More than 90% of labeled platelets were cleared from the circulation during torpor, followed by emergence during arousal which supports storage-and-release to govern thrombocytopenia in torpor. Furthermore, the low number of immature platelets, plasma level of interleukin-1α and normal numbers of megakaryocytes in bone marrow make platelet synthesis or megakaryocyte rupture via interleukin-1α unlikely to account for the recovery of platelet counts upon arousal. Finally, using large-scale electron microscopy we revealed platelets to accumulate in liver sinusoids, but not in spleen or lung, during torpor. These results thus demonstrate that platelet dynamics in hibernation are caused by storage and release of platelets, most likely by margination to the vessel wall in liver sinusoids. Translating the molecular mechanisms that govern platelet retention in the liver, may be of major relevance for hemostatic management in (accidental) hypothermia and for the development of novel anti-thrombotic strategies.
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Haley, Kristina M., Joseph E. Aslan, Garth W. Tormoen, Sandra M. Baker, Cassandra P. Loren, Jonathan Chernoff, and Owen J. T. McCarty. "The PAK Signaling System Links Rho Gtpase Activation to Platelet Lamellopodia Formation, Aggregation and Aggregate Stability Under Shear." Blood 120, no. 21 (November 16, 2012): 1060. http://dx.doi.org/10.1182/blood.v120.21.1060.1060.
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Abstract Abstract 1060 Platelets serve as the primary mediators of hemostasis and thrombosis, circulating as surveyors for gaps in vascular integrity. As platelets encounter exposed extracellular matrix proteins, receptors on the platelet surface trigger intracellular signaling events that result in rapid platelet activation and a complex rearrangement of platelet morphology to form filopodia and lamellipodia. Rac1, a member of the Rho GTPase family, has emerged as a key regulator in platelet actin dynamics. However, the specific downstream events following Rac1 activation that mediate platelet actin cytoskeleton reorganization remain ill-defined. The Rho GTPase, Rac, supports the autocatalytic activation of the p21 activated kinases, or PAKs, to mediate actin reorganization processes in focal adhesion formation and cell migration. Upon activation by GTP-bound Rac, the PAKs phosphorylate a number of substrates to coordinate actin dynamics. Platelets express a number of PAK isoforms, and like Rac, PAK has been shown to be activated as platelets spread on collagen in a Src and PI3K dependent manner. Furthermore, the adaptor protein SLP-76 has been proposed to potentiate PAK activity downstream of Rac activation to mediate platelet lamellipodia formation. However, the specific roles of PAK in platelet function have yet to be characterized. Thus we set out to elucidate the role of PAK in platelet function and to define the connection between Rac activation, PAK, and platelet cytoskeletal reorganization. Our initial experiments with mass spectrometry revealed that following platelet activation, Rac1 associates with a set of PAK effectors, GIT1, GEFH1, LIMK1, and Merlin. We next demonstrated a co-localization of Rac1 and PAK with actin at the leading edge of spread platelets on fibrinogen. In addition, inhibition of PAK signaling by two different pharmacologic inhibitors blocked platelet focal adhesion and lamellopodia formation on both fibrinogen and collagen. Inhibition of PAK signaling abrogated intracellular calcium mobilization in platelets, prevented platelet aggregation to the GPVI-agonist, CRP, and destabilized platelet lamellipodia, resulting in the retraction of lamellipodia in spread platelets. Finally, inhibition of PAK resulted in the disaggregation of platelet aggregates formed under shear flow conditions. Together, these results demonstrate that the PAK signaling system is a key orchestrator of platelet actin dynamics, linking Rho GTPase activation to PAK effector function and platelet lamellopodia formation, thus filling an important gap in the understanding of platelet actin cytoskeletal organization. In addition, these data characterize the integral role of PAK in platelet spreading, aggregation, and aggregate stability. Elucidating the mechanisms that mediate platelet spreading and aggregate formation may highlight important steps in the platelet activation cascade at which to pharmacologically intervene in order to inhibit or treat pathologic thrombi formation. Disclosures: No relevant conflicts of interest to declare.
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Stalker, Timothy J., Jie Wu, and Lawrence F. Brass. "Platelet Expression of a Genetically Encoded Calcium Indicator Reveals Platelet Activation Gradients in Real Time during Thrombus Formation in Vivo." Blood 124, no. 21 (December 6, 2014): 96. http://dx.doi.org/10.1182/blood.v124.21.96.96.
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Abstract Introduction: Recent studies have demonstrated that platelet activation during hemostatic thrombus formation in vivo is heterogeneous in time and space. We have previously shown that in response to a penetrating injury in the microcirculation platelet accumulation and activation are driven by gradients of soluble agonists emanating from the site of injury. These gradients result in a characteristic thrombus architecture in which a core of fully activated platelets that have released their alpha granules is overlaid by a shell of less activated platelets that frequently embolize. While dependent on ADP/P2Y12 signaling, the extent and dynamics of platelet activation in the shell region remain poorly understood. Here, we used intravital imaging of platelet cytosolic calcium concentration to examine platelet activation in real time following vascular injury in vivo. Methods: We generated transgenic mice expressing a genetically encoded calcium indicator (GCaMP3) specifically in megakaryocytes and platelets by crossing PF4-Cre mice with Ai38 mice carrying the GCaMP3 transgene. GCaMP3 fluorescence was visualized in platelets following laser-induced injury in mouse cremaster arterioles using spinning disk confocal intravital microscopy. Results: Rapid and dynamic changes in GCaMP3 fluorescence were observed during platelet accumulation following vascular injury. Platelets immediately adjacent to the site of injury exhibited a rapid and sustained increase in cytosolic calcium. Peak cytosolic calcium levels in the core region occurred within the first minute post-injury, prior to peak P-selectin expression. Platelets in the shell region were characterized by dynamic changes in cytosolic calcium at the level of individual platelets, with the appearance of transient “waves” of calcium signaling propagating among groups of platelets. At the population level, cytosolic calcium concentration was substantially lower in the shell region as compared to the core. Conclusions: Expression of a genetically encoded calcium indicator in platelets allows for the visualization of platelet activation events in real time in vivo. Platelets within the core region of a thrombus exhibit a rapid and sustained increase in cytosolic calcium concentration, indicating robust activation. In contrast, platelets in the shell region exhibit transient increases in cytosolic calcium indicating weak activation, consistent with their increased likelihood of embolization. The examination of platelet calcium signaling in vivo provides a sensitive readout of platelet activation that will shed new light on mechanisms regulating hemostasis and thrombosis, and may be useful in assessing the impact of anti-thrombotic agents on platelet function. Research support was provided by the American Heart Association and National Heart, Lung and Blood Institute. Disclosures Stalker: Medicines Company: Research Funding. Brass:Medicines Company: Research Funding.
Dissertations / Theses on the topic "Platelet dynamics/thrombosis"
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Lane, I. F. "The relationship between platelet-vessel wall interaction thrombosis and atherosclerosis." Thesis, University of Oxford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233551.
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Bark, David Lawrence Jr. "Mechanistic numerical study of trhombus growth." Thesis, Atlanta, Ga. : Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/22550.
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Andersen, Brandon Thomas. "Multi-Processor Computation of Thrombus Growth and Embolization in a Model of Blood-Biomaterial Interaction Based on Fluid Dynamics." BYU ScholarsArchive, 2012. https://scholarsarchive.byu.edu/etd/3465.
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This work describes the development and testing of a real-time three-dimensional computational fluid dynamics simulation of thrombosis and embolization to be used in the design of blood-contacting devices. Features of the model include the adhesion and aggregation of blood platelets on device material surfaces, shear and chemical activation of blood platelets, and embolization of platelet aggregates due to shear forces. As thrombus develops, blood is diverted from its regular flow field. If shear forces on a thrombus are sufficient to overcome the strength of adhesion, the thrombus is dislodged from the wall. Development of the model included preparing thrombosis and embolization routines to run in a parallel processing configuration, and estimating necessary parameters for the model including the adhesion strength of platelet conglomerations to the device surfaces and the criterion threshold for the coalescence of neighboring thrombi. Validation of the model shows that the effect of variations in geometry may be accurately predicted through computational simulation. This work is based on previous work by Paul Goodman, Daniel Lattin, Jeff Ashton, and Denzel Frost.
Book chapters on the topic "Platelet dynamics/thrombosis"
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Barkalow, Kurt L., Hervé Falet, and John Hartwig. "Dynamics of the platelet cytoskeleton." In Platelets in Thrombotic and Non-Thrombotic Disorders, 93–103. Cambridge University Press, 2002. http://dx.doi.org/10.1017/cbo9780511545283.007.
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White, Gilbert C., Harold R. Roberts, and Nigel S. Key. "The biology of haemostasis and thrombosis." In Oxford Textbook of Medicine, edited by Chris Hatton and Deborah Hay, 5490–509. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0543.
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Haemostasis—a component of the wound defence mechanism—is a process by which vessel wall components and platelets act in concert with procoagulant and anticoagulant proteins to form a plug of cells and cross-linked fibrin. The plug is later remodelled and replaced by new tissue as part of wound healing. These processes are very complex and involve highly controlled pathways of interaction between cells, glycans, and membrane-bound and soluble proteins of coagulation and fibrinolysis, as well as their cognate inhibitors. Thrombosis—this is an abnormal state leading to formation of a clot that partially or completely obstructs the flow of blood within the blood vessel; dislodgement leads to thromboembolism. To understand the biology of haemostasis and thrombosis, it is necessary to know the roles of the vessel wall, the platelets, the coagulation and fibrinolytic systems, and their respective inhibitors. Fibrinolysis and coagulation are interrelated: fibrin clots are normally lysed by plasmin locally released from plasminogen by the action of tissue plasminogen activator, and this process can be enhanced by some procoagulant factors (e.g. activated factor XII, and protein C). This system, so delicately controlled and normally maintained in a dynamic equilibrium, is strongly influenced by components involved in inflammatory and other defence mechanisms in the host. An integrated understanding of these processes offers the potential for improved means to predict the adverse complications of many diseases and ultimately to prevent their occurrence.
Conference papers on the topic "Platelet dynamics/thrombosis"
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Badimon, J. J., L. Badimon, A. Galvez, J. Camunas, and V. Fuster. "DYNAMICS AND LOCALIZATION OF PLATELET DEPOSITION ON A SYNTHETIC VASCULAR GRAFT: CONTINUOUS IMAGING." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643954.
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The in vivo dynamics of thrombus formation have not been extensively studied, mainly due to technical limitations. We assessed the dynamics and localization of platelet deposition on a prosthetic vascular graft for the first 24 hours after implantation in swine, with continuous monitoring during the initial 6 hours, and the effect of heparin. Polytetrafluoro-ethylene (PTFE) grafts (5cm. L × 0.5 cm. ID) were inplanted in one of the common carotids of 13 normal pigs; 8 received iv heparin (150uAg) perioperatively. 111 In-labelled autologous platelets were injected 5 min before reperfusion of the graft. From 10 min to 24 hrs after unclamping the vessel sequential gamma camera images of the neck were taken and stored in an on-line computer. Pinpoint analysis of the platelet deposition was performed by creating seven regions of interest of 5 × 5 pixels over both graft and contralateral carotid territories. We obtained the ratio of the 111 In-activity in each region of the graft, including both anastomoses, with respect to its contralateral homologous region. The ratios differed along the graft in both groups of animals, with maximal values at the anastomosis. Peak ratios were reached within 1 to 3 hrs, and were significatively lower in heparinized pigs (anastomosis: 1.95±0.36; graft: 1.3±0.66) than in rion-heparinized-pigs (anastomosis: 3.23±0.66; graft: 2.16±0.41; p<0.05). Heparinized pigs showed a progressive decrease of the ratios up to 24 hrs. In contrast, platelet deposition in non-heparinized-pigs continued up to 6 hrs. Patency at 24 hrs was 88% in heparinized-pigs versus 20% in non-heparinized-pigs. We conclude that computer assisted pinpoint analysis of platelet deposition may help to a better understanding of the thrombotic process differentiating platelet-graft interaction from platelet anastomosis interaction. The deposition of platelets and graft patency is strongly influenced by the stabilizing effect of procoagulant moieties, and the presence of the anastomosis (release of vessel wall procoagulant and platelet activating products and induction of blood flow disturbances) induces localized activation and deposition of platelets.
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Longmire, K., and M. M. Frojmovic. "PLATELET AGGREGATION DYNAMICS TO ADENOSINE DIPHOSPHATE IN NON-STIRRED SUSPENSIONS: LONG-RANGEINTERACTIONS FOR HUMAN, BUT NOT RABBIT, PLATELETS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644464.
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The simplest experimental approach for a theoretical description of platelet aggregation is based on kinetics of early multiplet formation (‹4 platelets per aggregate)occurring with diffusion-dependent particle collisions (no flow). The Smoluchowski theory was used to calculate collision efficiencies, αβ, from a linear plot of platelet particle count (Nt)−1 vs time (t) following addition of adenosine diphosphate (ADP) to citrated platelet-rich-plasma (PRP) for 7 human (H) and 2 rabbit (R) donors. A 0.1 ml sample of PRP was stirred with ADP for 0.5s, then immediately transferred to a 37°C bath for no-stir (diffusion) studies or further stirred with ADP for stir-induced aggregation studies. Samples were fixed with 0.5 ml 0.8% glutaraldehyde with particle count (Nt) determined with a resistive counter and % aggregation (PA) computed (reproducibility/sensitivity ‹ 5%). For stir conditions, R platelets were as sensitive and as rapidly aggregated by ADP (2-10 μM) as H platelets, with ∼ 1 s time lag for onset of PA. However, for no-stir conditions, linear regression analysis of data for ADP (5-10 μM) induced PA for H platelets for 0-30 s gave αβ = 7.5±4.6 (r = 0.9±0.05). Analysis at longer “diffusion” times showed a second phase (60-300 s) in some H donors with aB = 0.5±0.4 (4/9 donors), while R platelets showed only 1 phase with αβ = 0.65±0.15 (0-60 to 0-900 s) (r = 0.8±0.1). The ADP sensitivity ([ADP]½ corresponding to 50% of maximal changes) for the abnormally rapid PA in no stir H PRP for early times, measured over 0.4-100 μM range, was found to be ∼9 μM (5-17 μM range) and 3.5 μM (3-10 μM) for measurements respectively at 5-10 and 20-30s; these values were ∼ 3-8 × greater than lADPji measured for stirred suspensions for rate/extent of PA or rate of turbidometrically-measured macroaggregation (TA), while › [ADP] threshold for secondary aggregation in TA (10 H donors). These abnormally large aB values and their ADP sensitivity observed for human platelets are consistent with long-range interactions mediated by“chemotactic” agents released from the cells but distinct from normal dense granule release requiring macroaggregation, or by as yet uncharacterized membrane or polymetric bridges.
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Bluestein, Danny, João S. Soares, Peng Zhang, Chao Gao, Seetha Pothapragada, Na Zhang, Marvin J. Slepian, and Yuefan Deng. "Multiscale Modeling of Flow Induced Thrombogenicity Using Dissipative Particle Dynamics and Molecular Dynamics." In ASME 2013 2nd Global Congress on NanoEngineering for Medicine and Biology. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/nemb2013-93094.
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The coagulation cascade of blood may be initiated by flow induced platelet activation, which prompts clot formation in prosthetic cardiovascular devices and arterial disease processes. While platelet activation may be induced by biochemical agonists, shear stresses arising from pathological flow patterns enhance the propensity of platelets to activate and initiate the intrinsic pathway of coagulation, leading to thrombosis. Upon activation platelets undergo complex biochemical and morphological changes: organelles are centralized, membrane glycoproteins undergo conformational changes, and adhesive pseudopods are extended. Activated platelets polymerize fibrinogen into a fibrin network that enmeshes red blood cells. Activated platelets also cross-talk and aggregate to form thrombi. Current numerical simulations to model this complex process mostly treat blood as a continuum and solve the Navier-Stokes equations governing blood flow, coupled with diffusion-convection-reaction equations. It requires various complex constitutive relations or simplifying assumptions, and is limited to μm level scales. However, molecular mechanisms governing platelet shape change upon activation and their effect on rheological properties can be in the nm level scales. To address this challenge, a multiscale approach which departs from continuum approaches, may offer an effective means to bridge the gap between macroscopic flow and cellular scales. Molecular dynamics (MD) and dissipative particle dynamics (DPD) methods have been employed in recent years to simulate complex processes at the molecular scales, and various viscous fluids at low-to-high Reynolds numbers at mesoscopic scales. Such particle methods possess important properties at the mesoscopic scale: complex fluids with heterogeneous particles can be modeled, allowing the simulation of processes which are otherwise very difficult to solve by continuum approaches. It is becoming a powerful tool for simulating complex blood flow, red blood cells interactions, and platelet-mediated thrombosis involving platelet activation, aggregation, and adhesion.
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Bluestein, Danny, João S. Soares, Peng Zhang, Chao Gao, Seetha Pothapragada, Na Zhang, Marvin J. Slepian, and Yuefan Deng. "Multiscale Modeling of Flow Induced Thrombogenicity With Dissipative Particle Dynamics (DPD) and Molecular Dynamics (MD)." In ASME 2013 Conference on Frontiers in Medical Devices: Applications of Computer Modeling and Simulation. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/fmd2013-16176.
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The coagulation cascade of blood may be initiated by flow induced platelet activation, which prompts clot formation in prosthetic cardiovascular devices and arterial disease processes. While platelet activation may be induced by biochemical agonists, shear stresses arising from pathological flow patterns enhance the propensity of platelets to activate and initiate the intrinsic pathway of coagulation, leading to thrombosis. Upon activation platelets undergo complex biochemical and morphological changes: organelles are centralized, membrane glycoproteins undergo conformational changes, and adhesive pseudopods are extended. Activated platelets polymerize fibrinogen into a fibrin network that enmeshes red blood cells. Activated platelets also cross-talk and aggregate to form thrombi. Current numerical simulations to model this complex process mostly treat blood as a continuum and solve the Navier-Stokes equations governing blood flow, coupled with diffusion-convection-reaction equations. It requires various complex constitutive relations or simplifying assumptions, and is limited to μm level scales. However, molecular mechanisms governing platelet shape change upon activation and their effect on rheological properties can be in the nm level scales. To address this challenge, a multiscale approach which departs from continuum approaches, may offer an effective means to bridge the gap between macroscopic flow and cellular scales. Molecular dynamics (MD) and dissipative particle dynamics (DPD) methods have been employed in recent years to simulate complex processes at the molecular scales, and various viscous fluids at low-to-high Reynolds numbers at mesoscopic scales. Such particle methods possess important properties at the mesoscopic scale: complex fluids with heterogeneous particles can be modeled, allowing the simulation of processes which are otherwise very difficult to solve by continuum approaches. It is becoming a powerful tool for simulating complex blood flow, red blood cells interactions, and platelet-mediated thrombosis involving platelet activation, aggregation, and adhesion.
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Zhang, Peng, Jawaad Sheriff, João S. Soares, Chao Gao, Seetha Pothapragada, Na Zhang, Yuefan Deng, and Danny Bluestein. "Multiscale Modeling of Flow Induced Thrombogenicity Using Dissipative Particle Dynamics and Coarse Grained Molecular Dynamics." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14187.
Full textAbstract:
The coagulation cascade of blood may be initiated by flow induced platelet activation, which prompts clot formation in prosthetic cardiovascular devices and arterial disease processes. While platelet activation may be induced by biochemical agonists, shear stresses arising from pathological flow patterns enhance the propensity of platelets to activate and initiate the intrinsic pathway of coagulation, leading to thrombosis. Upon activation platelets undergo complex biochemical and morphological changes: organelles are centralized, membrane glycoproteins undergo conformational changes, and adhesive pseudopods are extended. Activated platelets polymerize fibrinogen into a fibrin network that enmeshes red blood cells. Activated platelets also cross-talk and aggregate to form thrombi. Current numerical simulations to model this complex process mostly treat blood as a continuum and solve the Navier-Stokes equations governing blood flow, coupled with diffusion-convection-reaction equations. It requires various complex constitutive relations or simplifying assumptions, and is limited to μm level scales. However, molecular mechanisms governing platelet shape change upon activation and their effect on rheological properties can be in the nm level scales. To address this challenge, a multiscale approach which departs from continuum approaches, may offer an effective means to bridge the gap between macroscopic flow and cellular scales. Coarse Grained Molecular dynamics (CGMD) and discrete/dissipative particle dynamics (DPD) methods have been employed in recent years to simulate complex processes at the molecular scales, and various viscous fluids at low-to-high Reynolds numbers at mesoscopic scales. Such particle methods possess important properties at the mesoscopic scale: complex fluids with heterogeneous particles can be modeled, allowing the simulation of processes which are otherwise very difficult to solve by continuum approaches. It is becoming a powerful tool for simulating complex blood flow, red blood cells interactions, and platelet-mediated thrombosis involving platelet activation, aggregation, and adhesion.
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Gear, A. R. L., and G. D. Jones. "SUB-SECOND CALCIUM DYNAMICS IN ADP AND THROMBIN-STIMULATED PLATELETS; ASSESSED BY A C0NTINU0US-EL0W APPROACH." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644531.
Full textAbstract:
There is now evidence that many platelet reactions begin within 1 sec of platelet stimulation. These include "shape change," aggregation and biochemical events such as protein phosphorylation. Our laboratory has devised quenched-flow approaches for following such early events (J Lab Clin Med 100, 866, 1982) and we have extended these to fluorimetric analyses of rapid calcium changes. A micro, flow-through cell, with a sensing volume of 0.1 μ1, is placed on line from the quenched-flow apparatus. Indo-1 loaded, human platelets are pumped through the system and reaction times from 0.25 sec can be followed. Ratioing emission changes at 400 and 480 nm, after excitation at 355 nm, provides an index of free calcium. ADP (10 μM) induced a rapid increase in Ca++ to about 1 μM by 1.5 sec, beginning near 0.3 sec. This was faster and greater than the first increase caused by thrombin (10U/ml). However, thrombin induced a second (> 5s) and larger increase in free platelet calcium. Control experiments where the Indo-1 loaded platelets were simply pumped through the 0.3 mm ID reaction tubing, revealed a slight increase above resting calcium values, indicating some shear-induced activation. The use of the continuous-flow fluorescent cell coupled to the quenched-flow apparatus enables following calcium dynamics under Theological conditions very close to those iui vivo.Correlations with other early events, such as protein phosphorylation, become possible. Supported by NIH HL-27014.
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Mousel, J. A., H. S. Udaykumar, and K. B. Chandran. "Multiscale Modeling of Platelet Dynamics in Blood Flow With Application to Thrombus Formation." In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-192780.
Full textAbstract:
From an averaged point of view, blood can often be treated computationally as a single-phase fluid of non-Newtonian character. Such a model may be appropriate if information regarding the bulk motion of the blood is all that is required. If, however, one seeks to describe the mechanisms leading to diseases such as thrombosis in the presence of foreign surfaces such as prosthesis, accurate predictions of platelet behavior in the dynamic environment of the blood are required. There are several effects that necessitate a careful treatment of platelet dynamics. For example, it is well known that the presence of red blood cells has a significant impact on radial distribution of platelets as well as the shear stress experienced by the platelets [1]. Therefore, the paths of and forces experienced by individual platelets are to be determined in order to predict the location and predilection for thrombus formation. However, since the length scales of the platelets are much smaller than the typical dimensions of the flow regions through which blood flows, it is not possible to capture platelet dynamics in a single-scale computation. Therefore, a multiscale technique for incorporating the dynamics of platelets and platelet-RBC interactions into large-scale flow simulations is required. We therefore examine a suspension of ellipsoidal and circular rigid particles that are representative of red blood cells and platelets carried in a Newtonian fluid to study the interaction or red blood cells and platelets.
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Palankar, R., M. Medvidov, J. Wesche, and A. Greinacher. "Single-molecule Labeling and Tracking of FcγRIIA on Human Platelets Reveals Differential Mobility Dynamics, which Depends on Platelet Cytoskeletal Integrity." In 63rd Annual Meeting of the Society of Thrombosis and Haemostasis Research. Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-1680095.
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Palankar, R., M. Medvidov, J. Wesche, and A. Greinacher. "Single-molecule Labeling and Tracking of FcγRIIA on Human Platelets Reveals Differential Mobility Dynamics, which Depends on Platelet Cytoskeletal Integrity." In 63rd Annual Meeting of the Society of Thrombosis and Haemostasis Research. Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-1680196.
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Zhao, Rui, Joie Marhefka, Marina Kameneva, and James Antaki. "The Effect of Red Cell Dynamics on Platelet Spatial Distribution in Sudden Expansion." In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-176027.
Full textAbstract:
Thrombosis is a common complication associated with blood contacting devices [1]. Platelets often (or preferably) deposit in specific regions which contain complex flow featuring separations, recirculation zones and stagnation points [2, 3].