Academic literature on the topic 'Platelet response'
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Journal articles on the topic "Platelet response"
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DeHelian, Daniel, Shuchi Gupta, Jie Wu, et al. "RGS10 and RGS18 differentially limit platelet activation, promote platelet production, and prolong platelet survival." Blood 136, no. 15 (2020): 1773–82. http://dx.doi.org/10.1182/blood.2019003251.
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Abstract G protein–coupled receptors are critical mediators of platelet activation whose signaling can be modulated by members of the regulator of G protein signaling (RGS) family. The 2 most abundant RGS proteins in human and mouse platelets are RGS10 and RGS18. While each has been studied individually, critical questions remain about the overall impact of this mode of regulation in platelets. Here, we report that mice missing both proteins show reduced platelet survival and a 40% decrease in platelet count that can be partially reversed with aspirin and a P2Y12 antagonist. Their platelets have increased basal (TREM)-like transcript-1 expression, a leftward shift in the dose/response for a thrombin receptor–activating peptide, an increased maximum response to adenosine 5′-diphosphate and TxA2, and a greatly exaggerated response to penetrating injuries in vivo. Neither of the individual knockouts displays this constellation of findings. RGS10−/− platelets have an enhanced response to agonists in vitro, but platelet count and survival are normal. RGS18−/− mice have a 15% reduction in platelet count that is not affected by antiplatelet agents, nearly normal responses to platelet agonists, and normal platelet survival. Megakaryocyte number and ploidy are normal in all 3 mouse lines, but platelet recovery from severe acute thrombocytopenia is slower in RGS18−/− and RGS10−/−18−/− mice. Collectively, these results show that RGS10 and RGS18 have complementary roles in platelets. Removing both at the same time discloses the extent to which this regulatory mechanism normally controls platelet reactivity in vivo, modulates the hemostatic response to injury, promotes platelet production, and prolongs platelet survival.
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Kim, Soochong, and Satya P. Kunapuli. "Negative Regulation of Gq-Mediated Pathways in Platelets by G12/13 Pathways through Fyn Kinase." Blood 112, no. 11 (2008): 2854. http://dx.doi.org/10.1182/blood.v112.11.2854.2854.
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Abstract Platelets contain high levels of Src family kinases (SFKs) suggesting an important role for these enzymes in platelet function. In this study, we have investigated the regulation of platelet function by SFKs downstream of G12/13 pathways. Calcium-independent platelet shape change induced by selective G12/13 stimulation with YFLLRNP was potentiated with a small mobilization of intracellular calcium in the presence of SFK inhibitors PP1 or PP2, which was abolished by the chelation of intracellular calcium, suggesting that SFKs downstream of G12/13 negatively regulate calcium mobilization in platelets. In addition, PP1 or PP2 caused a leftward shift of human platelet aggregation, secretion, and calcium response induced by low concentrations of agonists that activate platelets through G12/13 signaling such as PAR1-activating peptide SFLLRN and PAR4-activating peptide AYPGKF. However, 2-MeSADP-induced calcium response and platelet aggregation were not affected by the presence of PP1 or PP2, suggesting that SFKs downstream of G12/13, but not Gq/Gi, pathways are involved in this platelet response. Moreover, platelet aggregation and secretion caused by combined stimulation of G12/13 and Gi/Gz (YFLLRNP + 2-MeSADP with P2Y1 antagonist/epinephrine) were also potentiated in the presence of PP1 or PP2 confirming the contribution of SFKs downstream of G12/13 as a negative regulator to platelet activation. Potentiation of platelet aggregation in the presence of SFK inhibitors was not affected in the presence of GF109203X, while PP2 failed to potentiate platelet aggregation in the presence of 5,5′-dimethyl-BAPTA indicating that potentiation of cytosolic calcium may have an important role in this enhanced platelet responses by SFK inhibition. Moreover, PP1 or PP2 failed to potentiate platelet responses in the presence of Gq selective inhibitor YM-254890 or in Gq-deficient platelets, indicating that SFKs negatively regulate platelet responses through modulation of Gq signaling pathways. Importantly, AYPGKF-induced platelet aggregation, secretion, and calcium response were potentiated in Fyn-, but not in Lyn-, deficient platelets compared to the wild-type mouse platelets, whereas 2-MeSADP-induced platelet response was not affected in these platelets. We conclude that SFKs activated downstream of G12/13, but not Gq/Gi, pathways negatively regulate platelet responses by inhibiting intracellular calcium mobilization in platelets through Gq signaling pathways. Specifically, we define that Fyn plays a major role in this negatively regulatory pathway.
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Naylor-Adamson, Leigh, Zoe Booth, Simon Hart та ін. "Bruton's Tyrosine Kinase Inhibitors Impair Fcγriia-Mediated Responses of Healthy Donor Platelets and Chronic Lymphocytic Leukaemia Derived Platelets to Bacteria". Blood 136, Supplement 1 (2020): 1. http://dx.doi.org/10.1182/blood-2020-142624.
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Platelets play a key role in innate immunity and can interact with bacteria through multiple molecular mechanisms. One key receptor for platelet-bacteria interactions is FcγRIIa, a low affinity IgG immune receptor found on the surface of platelets, which is associated with platelet aggregation, phagocytosis and the release of bactericidal substances and cytokines from alpha and dense granules. The signalling pathways that regulate FcγRIIa mediated platelet responses to bacteria are not fully understood. Downstream of the FcγRIIa receptor is the protein Bruton's tyrosine kinase (Btk) and potentially other Tec family kinases, yet the role of these kinases in platelet-bacteria interactions is unknown. Btk is a therapeutic target in chronic lymphocytic leukaemia (CLL) with inhibitors of Btk (iBtks) including ibrutinib and acalabrutinib. However, iBtks have off-target effects on platelets, inhibiting aggregation with associated haemorrhagic side effects. iBtk treatment is also associated with a higher incidence of infection in CLL patients. The effect of iBtks on platelet immune function has not been evaluated. We hypothesise that Btk has a role in platelet FcγRIIa signalling in response to bacterial agonists, and that iBtks inhibit such responses, contributing towards the increased risk of infection seen with such therapies in CLL. We show that ibrutinib and acalabrutinib inhibit healthy donor FcγRIIa-mediated platelet aggregation, alpha and dense granule release in response to incubation with Staphylococcus aureus and Escherichia coli, and also in response to FcγRIIa crosslinking with the monoclonal antibody IV.3 (anti-FcγRIIa). The observed lack of granule secretion will reduce the bactericidal substances released by the platelet, as well as the amount of cytokine and chemokine secretion limiting cross-talk with other immune cells. Phosphorylation of Btk at tyrosine 223 (a marker of Btk activation) was detected in response to FcγRIIa agonists, and was inhibited by both ibrutinib and acalabrutinib. Little is known about the effect of iBtk treatment on CLL-platelet responses to bacteria. CLL patients tend to be on concurrent medications for comorbid conditions that could alter platelet responses. We show that treatment-naïve and ibrutinib-treated CLL platelets have aggregation and alpha granule release to thrombin receptor activator peptide 6 and ADP comparable to healthy controls, indicating that CLL platelet responses to these FcγRIIa-independent agonists are normal. Moreover, platelets derived from iBtk naïve CLL patients aggregate normally to bacteria in the presence of autologous plasma. However, platelets from ibrutinib-treated CLL patients have significantly inhibited aggregation and alpha granule release in response to S.aureus, E.coli, and IV.3 crosslinking. Moreover, Btk is phosphorylated at Y223 in response to bacterial agonists in treatment-naïve, but not in ibrutinib-treated CLL platelets, highlighting the lack of Btk activation in iBtk-treated patients. An X-linked agammaglobulinaemia (XLA) patient with a known Btk loss of function mutation was examined to investigate if Btk is vital for the FcγRIIa pathway. XLA-derived platelets aggregated normally in response to multiple bacterial species, suggesting Btk is redundant in mediating platelet aggregatory responses to bacteria. These results suggest that other Tec family kinases might have a role in platelet FcγRIIa activation to bacteria, which could be affected by iBtk treatment too. In conclusion, we propose that iBtks impair the FcγRIIa pathway in platelets, reducing platelet-bacteria responses, possibly contributing to the increased risk of infections in observed in CLL. Disclosures No relevant conflicts of interest to declare.
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Auger, Jocelyn, Imke Munnix, Judith Cosemans, and Johan Heemskerk. "Platelet response heterogeneity in thrombus formation." Thrombosis and Haemostasis 102, no. 12 (2009): 1149–56. http://dx.doi.org/10.1160/th09-05-0289.
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SummaryVascular injury leads to formation of a structured thrombus as a consequence of platelet activation and aggregation, thrombin and fibrin formation, and trapping of leukocytes and red cells. This review summarises current evidence for heterogeneity of platelet responses and functions in the thrombus-forming process. Environmental factors contribute to response heterogeneity, as the platelets in a thrombus adhere to different substrates, and sense specific (ant)agonists and rheological conditions. Contraction of platelets and interaction with fibrin and other blood cells cause further response variation. On the other hand, response heterogeneity can also be due to intrinsic differences between platelets in age and in receptor and signalling proteins. As a result, at least three subpopulations of platelets are formed in a thrombus: aggregating platelets with (reversible) integrin activation, procoagulant (coated) platelets exposing phosphatidylserine and binding coagulation factors, and contracting platelets with cell-cell contacts. This recognition of thrombus heterogeneity has implications for the use and development of antiplatelet medication.
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Norol, Françoise, Philippe Bierling, Françoise Roudot-Thoraval, et al. "Platelet Transfusion: A Dose-Response Study." Blood 92, no. 4 (1998): 1448–53. http://dx.doi.org/10.1182/blood.v92.4.1448.
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Abstract Early recommendations on prophylactic transfusion of thrombocytopenic patients involved a standard platelet dose of about 0.5 × 1011/10 kg body weight. Given the lack of data supporting this dose, we prospectively studied the dose response to platelet transfusions in adults and children with hematologic malignancies. Each patient received, in similar clinical conditions, a medium, high, and very high dose of fresh (< 24 hours old) ABO-compatible platelets, in the form of apheresis platelet concentrates (APC). For the adults, the medium dose was defined as APC containing between 4 and 6 × 1011 platelets, the high dose between 6 and 8 × 1011, and the very high dose > 8 × 1011; for the children, the three doses corresponded to 2 to 4, 4 to 6, and > 6 × 1011 platelets. The end points were the platelet increment, platelet recovery, and the transfusion interval, and the results were compared with a paired t-test. Sixty-nine adults and 13 children could be assessed. Recoveries in the adults were similar with the three doses (from 28% to 30%), but the high and very high doses led to a significantly better platelet increment (52 and 61 × 109/L, respectively) than the medium dose (33 × 109/L, P < .01). The main difference was in the transfusion interval, which increased with the dose of platelets transfused, from 2.6 days with the medium dose to 3.3 and 4.1 days with the high and very high doses, respectively (P< .01). The positive effect of the high dose was observed regardless of pretransfusional clinical status, but was more marked in patients with no clinical factors known to impair platelet recovery. In these patients, a platelet dose of 0.07 × 1011 per kg of body weight led to a transfusion interval of more than 2 days in 95% of cases. In patients with clinical factors favoring platelet consumption, the proportion of transfusions yielding an optimal platelet increment and transfusion interval increased with the dose of platelets.The platelet dose-effect was also significant in the children, in whom the high and very high doses led to 1.5-fold to twofold higher posttransfusion platelet counts and transfusion intervals. We conclude that transfusion of high platelet doses can reduce the number of platelet concentrates required by thrombocytopenic patients and significantly reduce donor exposure. © 1998 by The American Society of Hematology.
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Norol, Françoise, Philippe Bierling, Françoise Roudot-Thoraval, et al. "Platelet Transfusion: A Dose-Response Study." Blood 92, no. 4 (1998): 1448–53. http://dx.doi.org/10.1182/blood.v92.4.1448.416k10_1448_1453.
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Early recommendations on prophylactic transfusion of thrombocytopenic patients involved a standard platelet dose of about 0.5 × 1011/10 kg body weight. Given the lack of data supporting this dose, we prospectively studied the dose response to platelet transfusions in adults and children with hematologic malignancies. Each patient received, in similar clinical conditions, a medium, high, and very high dose of fresh (< 24 hours old) ABO-compatible platelets, in the form of apheresis platelet concentrates (APC). For the adults, the medium dose was defined as APC containing between 4 and 6 × 1011 platelets, the high dose between 6 and 8 × 1011, and the very high dose > 8 × 1011; for the children, the three doses corresponded to 2 to 4, 4 to 6, and > 6 × 1011 platelets. The end points were the platelet increment, platelet recovery, and the transfusion interval, and the results were compared with a paired t-test. Sixty-nine adults and 13 children could be assessed. Recoveries in the adults were similar with the three doses (from 28% to 30%), but the high and very high doses led to a significantly better platelet increment (52 and 61 × 109/L, respectively) than the medium dose (33 × 109/L, P < .01). The main difference was in the transfusion interval, which increased with the dose of platelets transfused, from 2.6 days with the medium dose to 3.3 and 4.1 days with the high and very high doses, respectively (P< .01). The positive effect of the high dose was observed regardless of pretransfusional clinical status, but was more marked in patients with no clinical factors known to impair platelet recovery. In these patients, a platelet dose of 0.07 × 1011 per kg of body weight led to a transfusion interval of more than 2 days in 95% of cases. In patients with clinical factors favoring platelet consumption, the proportion of transfusions yielding an optimal platelet increment and transfusion interval increased with the dose of platelets.The platelet dose-effect was also significant in the children, in whom the high and very high doses led to 1.5-fold to twofold higher posttransfusion platelet counts and transfusion intervals. We conclude that transfusion of high platelet doses can reduce the number of platelet concentrates required by thrombocytopenic patients and significantly reduce donor exposure. © 1998 by The American Society of Hematology.
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Chouchane, Osoul, Valentine Léopold, Christine C. A. van Linge, et al. "Role of Liver Kinase 1B in Platelet Activation and Host Defense During Klebsiella pneumoniae-Induced Pneumosepsis." International Journal of Molecular Sciences 26, no. 8 (2025): 3714. https://doi.org/10.3390/ijms26083714.
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Pneumonia is the most common cause of sepsis, with Klebsiella pneumoniae frequently implicated as a causative pathogen. Platelets play a crucial role in host defense during sepsis, and their activation is essential for effective immune responses, which is at least in part induced through activation of the collagen receptor glycoprotein (GP)VI. Platelets require energy for their activation, and Liver kinase B1 (LKB1) is a key regulator of energy metabolism. We sought to determine the role of LKB1 in platelet function and host response during K. pneumoniae-induced pneumosepsis. Platelet-specific-Lkb1-deficient mice were generated and compared to control littermates. Platelet counts were unaffected by Lkb1 deficiency in naïve mice. However, Lkb1-deficient platelets exhibited significant hyperreactivity to GPVI stimulation, an effect not observed after stimulation of the thrombin receptor protease-activated receptor 4. During K. pneumoniae infection, platelets of both Lkb1-deficient and control mice became equally hyporesponsive to GPVI stimulation, without differences between genotypes. Platelet-specific Lkb1 deficiency did not alter bacterial outgrowth or dissemination, inflammatory responses, or lung pathology. These findings suggest that while Lkb1 plays a role in regulating platelet activation in response to GPVI stimulation, it does not significantly impact platelet activation or the host response during pneumonia-induced sepsis.
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Cloutier, Nathalie, Isabelle Allaeys, Genevieve Marcoux, et al. "Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration." Proceedings of the National Academy of Sciences 115, no. 7 (2018): E1550—E1559. http://dx.doi.org/10.1073/pnas.1720553115.
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There is a growing appreciation for the contribution of platelets to immunity; however, our knowledge mostly relies on platelet functions associated with vascular injury and the prevention of bleeding. Circulating immune complexes (ICs) contribute to both chronic and acute inflammation in a multitude of clinical conditions. Herein, we scrutinized platelet responses to systemic ICs in the absence of tissue and endothelial wall injury. Platelet activation by circulating ICs through a mechanism requiring expression of platelet Fcγ receptor IIA resulted in the induction of systemic shock. IC-driven shock was dependent on release of serotonin from platelet-dense granules secondary to platelet outside-in signaling by αIIbβ3 and its ligand fibrinogen. While activated platelets sequestered in the lungs and leaky vasculature of the blood–brain barrier, platelets also sequestered in the absence of shock in mice lacking peripheral serotonin. Unexpectedly, platelets returned to the blood circulation with emptied granules and were thereby ineffective at promoting subsequent systemic shock, although they still underwent sequestration. We propose that in response to circulating ICs, platelets are a crucial mediator of the inflammatory response highly relevant to sepsis, viremia, and anaphylaxis. In addition, platelets recirculate after degranulation and sequestration, demonstrating that in adaptive immunity implicating antibody responses, activated platelets are longer lived than anticipated and may explain platelet count fluctuations in IC-driven diseases.
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Page, Martin J., and Etheresia Pretorius. "A Champion of Host Defense: A Generic Large-Scale Cause for Platelet Dysfunction and Depletion in Infection." Seminars in Thrombosis and Hemostasis 46, no. 03 (2020): 302–19. http://dx.doi.org/10.1055/s-0040-1708827.
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AbstractThrombocytopenia is commonly associated with sepsis and infections, which in turn are characterized by a profound immune reaction to the invading pathogen. Platelets are one of the cellular entities that exert considerable immune, antibacterial, and antiviral actions, and are therefore active participants in the host response. Platelets are sensitive to surrounding inflammatory stimuli and contribute to the immune response by multiple mechanisms, including endowing the endothelium with a proinflammatory phenotype, enhancing and amplifying leukocyte recruitment and inflammation, promoting the effector functions of immune cells, and ensuring an optimal adaptive immune response. During infection, pathogens and their products influence the platelet response and can even be toxic. However, platelets are able to sense and engage bacteria and viruses to assist in their removal and destruction. Platelets greatly contribute to host defense by multiple mechanisms, including forming immune complexes and aggregates, shedding their granular content, and internalizing pathogens and subsequently being marked for removal. These processes, and the nature of platelet function in general, cause the platelet to be irreversibly consumed in the execution of its duty. An exaggerated systemic inflammatory response to infection can drive platelet dysfunction, where platelets are inappropriately activated and face immunological destruction. While thrombocytopenia may arise by condition-specific mechanisms that cause an imbalance between platelet production and removal, this review evaluates a generic large-scale mechanism for platelet depletion as a repercussion of its involvement at the nexus of responses to infection.
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Stalker, Timothy J. "Platelet Activation Gradients During Thrombus Formation." Blood 126, no. 23 (2015): SCI—13—SCI—13. http://dx.doi.org/10.1182/blood.v126.23.sci-13.sci-13.
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The hemostatic response requires the tightly regulated interaction of the coagulation system, platelets, other blood cells and components of the vessel wall at a site of vascular injury. The dysregulation of this response may result in excessive bleeding if the response is impaired, and pathologic thrombosis with vessel occlusion and tissue ischemia if the response is overly robust. Extensive studies over the past decades have sought to unravel the regulatory mechanisms that coordinate the multiple biochemical and cellular responses in time and space to ensure that an optimal response to vascular damage is achieved. We and others have observed that platelet activation at a site of injury in vivo is heterogeneous, with a gradient of platelet activation extending from the site of injury. Platelets immediately adjacent to the injured vessel wall are densely packed and fully activated forming a stably adherent core region. This stable core is overlaid by a shell of less activated platelets that are more loosely packed. Genetic and pharmacologic studies have shown that the formation of these regions is dependent on partially overlapping gradients of distinct platelet agonists, with ADP serving as a mediator of platelet recruitment and retention in the shell region, and thrombin necessary for full platelet activation in the core region. The distribution of platelet agonists and other plasma solutes in time and space is in turn determined in part by their transport in the plasma microenvironments that evolve as platelets accumulate. Platelet mass consolidation and the subsequent narrowing of the gaps between platelets are important mechanisms by which plasma solutes are retained within the platelet mass to promote platelet activation. Consolidation also regulates the escape of plasma and platelet-derived bioactive molecules into the extravascular space. These studies and others examining how cellular, biochemical and physical factors are integrated to shape the optimal response to vascular injury in vivo will be discussed. Disclosures No relevant conflicts of interest to declare.
Dissertations / Theses on the topic "Platelet response"
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Murphy, Christine Therese. "Mechanisms of stimulus-response coupling in platelet-activating factor stimulated platelets." Thesis, University of Bath, 1992. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304999.
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Rattray, Andrew. "Platelet response to haemodynamic shear forces." Thesis, University of Liverpool, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367819.
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Muller, Michael John. "Modulation of the response to cutaneous injury /." [St. Lucia, Qld.], 2000. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16146.pdf.
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Navaratnam, K. "Platelet function and response to low-dose aspirin in pregnancy." Thesis, University of Liverpool, 2017. http://livrepository.liverpool.ac.uk/3009774/.
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Pre-eclampsia is a serious multisystem disorder unique to pregnant women and associated with significant maternal and perinatal morbidity and mortality worldwide. Despite the investment of decades of basic science and clinical research, the pathophysiology of pre-eclampsia has been incompletely illustrated. In low doses, the cyclooxygenase inhibitor and antiplatelet, aspirin, can redress the thromboxane/prostacyclin imbalance observed in pregnancies affected by pre-eclampsia. Low-dose aspirin is currently recommended for high risk pregnancies in many countries, despite affording only modest overall risk reduction. It has been demonstrated that aspirin-treated individuals experience variable antiplatelet and clinical effects, with ‘non-responders’ having a preponderance for adverse clinical outcomes. The aim of this research was to investigate whether aspirin non-responsiveness exists in pregnant women at high risk of pre-eclampsia and assess whether platelet response to aspirin relates to markers of placental function and/or adverse clinical outcomes. An additional aim was to conduct an unbiased genome-wide assessment of genetic factors which may influence an individual’s response to aspirin. This was made possible by first establishing reference ranges for cyclooxygenase-selective platelet function in pregnancy and developing nuclear magnetic resonance and liquid chromatography mass spectrometry protocols to detect aspirin metabolites and determine adherence. Women at high risk of pre-eclampsia, according to National Institute of Health and Care Excellence criteria, were assessed longitudinally for adherence and platelet function. With exact adherence assessments and cyclooxygenase-selective platelet function testing, aspirin non-responsiveness could not be identified. Additionally, there were no significant associations between platelet response to aspirin, markers of placental function, genetic factors and adverse clinical outcomes. However, a significant proportion of women exhibited variable response to low-dose aspirin, changing their response status throughout their pregnancies. This variable response strongly suggests suboptimal aspirin adherence and/or suboptimal dosing in this population. With the recent findings of increased reduction in the risk of pre-eclampsia with higher doses of aspirin, there is now a valuable opportunity to deepen our understanding of the pharmacokinetics and pharmacodynamics of aspirin in pregnancy. Advances in technology available for genomics and access to biobanked maternal DNA from high-quality, well-phenotyped cohorts provide a strong foundation from which to examine pre-eclampsia disease genomics.
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Allen, David L. "A study of the Human Platelet Antigen 1a (HPA-1a) antibody response in neonatal alloimmune thrombocytopenia (NAIT)." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:44a10539-de5d-44dc-9c51-5f43cf3c3a82.
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Neonatal alloimmune thrombocytopenia (NAIT) is caused by maternal alloantibodies against fetal platelet antigens inherited from the father and which are absent from maternal platelets. In Caucasians, antibodies against the Leu33 (HPA-1a) polymorphism of integrin β3 (part of the platelet αIIbβ3 complex) account for >70% of cases. Antenatal screening for these antibodies does not currently take place in the UK, partly because of the absence of sensitive, predictive tests. We hypothesized that the poor sensitivity and predictive abilities of current assays are due to the use of β3 in an inappropriate conformation, resulting in sub-optimal binding of HPA-1a antibodies. We hypothesized firstly that in vitro induced changes to αIIbβ3 might alter accessibility of the HPA-1a epitopes to alloantibodies, thus reducing assay sensitivity. Secondly, we hypothesized that HPA-1a antibodies are stimulated by, and preferentially recognise, β3 in association with αv, a molecule present on placental syncytiotrophoblasts, and that reactivity against platelet αIIbβ3 reflects only cross-reactivity with αvβ3. Our first hypothesis was proven by demonstrating that use of the cation chelating compound EDTA, used by many diagnostic laboratories as a component of assay reagents or present in blood samples as anticoagulant, resulted in significantly reduced assay sensitivity. These findings were confirmed in an international workshop. Support for our second hypothesis was provided by demonstrating enhanced reactivity of a small panel of examples of anti-HPA-1a against αvβ3 compared to αIIbβ3 and by molecular modelling data. We also showed that HPA-1a antibodies can inhibit platelet function by using a novel application of the ROTEM® delta thromboelastograph and an immunofluorescence assay in which we demonstrated blocking of platelet function using a monoclonal antibody, PAC-1, that binds only to activated αIIbβ3. These studies provide possible explanations for the poor sensitivity and predictive abilities of current assays and suggest further areas for research.
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Järemo, Petter. "Platelets and the inflammatory response in coronary heart disease /." Linköping, 2003. http://www.bibl.liu.se/liupubl/disp/disp2003/med816s.pdf.
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Barbosa, Alzira Maria de Castro. "Chronic immune thrombocytopenic purpura and infection Helicobacter pylori: platelet response to the bacteria elimination of treatment." Universidade Federal do CearÃ, 2015. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=16378.
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Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico<br>The Chronic Immune Thrombocytopenic Purpura (ITPc) is a condition caused by autoimmune response resulting awareness of platelets by self antiplatelet antibodies, causing lysis of platelets. Infection with H. pylori has been shown to likely factor for the development of PTIc, with possible platelet response relationship in PTIc after treatment of bacterial eradication. The objective was to evaluate possible effects of eradication of Helicobacter pylori in the number of platelets of patients with PTIC patients at the University Hospital Walter CantÃdio. Were invited to participate in the study 29 patients with PTIc, 15 remained and all were treated for H. pylori and were followed for a period of 6 months to a year for clinical evaluation and platelet count. All patients underwent endoscopy for diagnosis of infection and, after treatment, held breath test to confirm eradication. PCR was performed for the presence of H. pylori cagA gene. Of the 15 patients 01 (6.6%) were male and 14 (93.3%) were female, the mean age was 47.7 years (27-68), the mean disease duration was 7.43 years (1-25). After the treatment, 13 patients (86.7%) eradicated H. pylori 04 (30.7%) had clinical response; and 03 (75.0%) complete response and 01 (25.0%) partial response to PTIc. It was possible to evaluate the presence of H. pylori CagA gene in 09 patients strains, 06 of these (54.5%) had CagA-positive strains. Of the 04 patients of the group who responded to treatment, 03 (75.0%) were cagA-positive. The treatment for eradication of Helicobacter pylori increased the number of platelets in 30% of patients with PTIc after six months of follow-up of these patients.<br>A PÃrpura TrombocitopÃnica ImunolÃgica CrÃnica (PTIc) à uma afecÃÃo causada por resposta auto-imune decorrente da sensibilizaÃÃo das plaquetas por auto anticorpos antiplaquetÃrios, causando lise das plaquetas. A infecÃÃo pelo H. pylori tem sido mostrada como provÃvel fator para o desenvolvimento de PTIc, com possÃvel relaÃÃo de resposta plaquetÃria na PTIc apÃs o tratamento de erradicaÃÃo da bactÃria. O objetivo foi avaliar possÃveis efeitos da erradicaÃÃo do Helicobacter pylori no nÃmero de plaquetas dos pacientes com PTIc atendidos no Hospital UniversitÃrio Walter CantÃdio. Foram convidados a participar do estudo 29 pacientes com PTIc, 15 permaneceram e todos foram tratados para o H. pylori, sendo acompanhados por um perÃodo de 6 meses a um ano para a avaliaÃÃo clÃnica e contagem de plaquetas. Todos realizaram endoscopia digestiva para diagnÃstico da infecÃÃo e, apÃs o tratamento, realizaram teste respiratÃrio para confirmaÃÃo da erradicaÃÃo. Foi realizado PCR para averiguar a presenÃa do gene cagA do H. pylori. Dos 15 pacientes tratados 01 (6,6%) era do gÃnero masculino e 14 (93,3%) foram do gÃnero feminino, a mÃdia de idade foi de 47,7 anos (27-68), O tempo mÃdio de doenÃa foi de 7,43 anos (1-25). ApÃs o tratamento, 13 pacientes (86,7%), erradicaram o H. pylori, 04 (30,7%) obtiveram reposta clÃnica; sendo 03 (75,0%) resposta completa e 01 (25,0%) resposta parcial à PTIc. Foi possÃvel avaliar a presenÃa do gene cagA do H. pylori em cepas de 09 pacientes, desses 06 (54,5%) apresentaram cepas cagA-positivas. Dos 04 pacientes do grupo que responderam ao tratamento, 03 (75,0%) foram cagA-positivos. O tratamento para erradicaÃÃo do H.pylori aumentou de forma sustentada, mais de seis meses de seguimento, o nÃmero de plaquetas dos pacientes com PTIc, em trinta por cento dos pacientes avaliados. NÃo houve associaÃÃo estatÃstica significativa com nenhum dos fatores de risco avaliados, tais como, idade, gÃnero e tempo de doenÃa dos portadores e presenÃa do gene cagA.
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Narayanan, Padmini. "Interleukin 1 Receptor1 signaling in Platelet Inflammatory responses Interleukin-1ß processing and secretion." Cleveland State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=csu1425911007.
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Nijm, Johnny. "Inflammation and cortisol response in coronary artery disease /." Linköping : Univ, 2007. http://www.bibl.liu.se/liupubl/disp/disp2007/med1037s.pdf.
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Balasubramaniam, Karthik. "Platelet dependent thrombosis, blood thrombogenicity and response to antiplatelet therapy in health, ageing and type 2 diabetes mellitus." Thesis, University of Newcastle upon Tyne, 2016. http://hdl.handle.net/10443/3499.
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Elderly and type 2 diabetes mellitus (T2DM) patients with stable coronary artery disease (CAD) have increased risk of atherothrombotic events despite recommended secondary prevention therapy. High platelet reactivity drives this risk. Novel approaches to antiplatelet therapy are needed. Objectives: To: determine the effect of age and T2DM on blood thrombogenicity and response to dual antiplatelet therapy in stable CAD assess the effect of changes in platelet count on thrombus quantity and quality with Rafigrelide Methods: Study 1: Patients with stable CAD, 4 groups: age < 75 non-DM, age≥75 T2DM, age≥75 non-DM and age<75 T2DM studied at baseline and one week after clopidogrel. I performed Badimon chamber study, thromboelastography, VerifyNow® and Multiplate® aggregometry, coagulation and inflammatory biomarkers and scanning electron microscopy. Study 2: Twelve volunteers took Rafigrelide (novel platelet lowering agent) singly and then with aspirin. I performed Badimon chamber study and thromboelastography at pre-defined intervals. Results: Study 1: At baseline and after clopidogrel therapy, there was no difference in thrombus area between the four groups. Serum TNFα levels were higher in elderly T2DM patients. Other coagulation and inflammatory markers were similar between the groups. Clopidogrel reduced thrombus area, lowered platelet content of thrombus and increased fibrin diameter and density in all four groups. Elderly and T2DM patients demonstrated high platelet reactivity and hyporesponsiveness to clopidogrel. Significant reduction in thrombus area was demonstrated both in good- and hypo-responders to clopidogrel. Point of care tests and thrombus area showed no correlation. Post chamber blood confirmed release of P selectin, CD40 ligand and PAI-1 from activated platelets. ii Study 2: Rafigrelide reduced platelet count and thrombus area, delayed initiation of clot formation and reduced over all clot strength. Platelet count positively correlated with thrombus area. Conclusion: Elderly and T2DM patients had similar over all blood thrombogenicity but higher platelet reactivity when compared to young and non-diabetic patients. Addition of clopidogrel reduced thrombus area with ultrastructural changes in fibrin favouring fibrinolysis. Reduction in platelet count with Rafigrelide reduced thrombus formation and lowered viscoelastic strength. Dual antiplatelet therapy and novel therapeutic strategies may reduce future thrombotic risk in these high risk populations.
Books on the topic "Platelet response"
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J, Westwick, ed. Mechanisms of stimulus-response coupling in platelets. Plenum Press, 1985.
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Westwick, J., M. F. Scully, D. E. MacIntyre, and V. V. Kakkar, eds. Mechanisms of Stimulus—Response Coupling in Platelets. Springer US, 1986. http://dx.doi.org/10.1007/978-1-4615-9442-0.
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Curry, Nicola, and Raza Alikhan. Normal platelet function. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0281.
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The platelet is a small (2–4 µm in diameter), discoid, anucleate cell that circulates in the blood. In health, it plays a vital role in haemostasis, and in disease it contributes to disorders of bleeding and thrombosis. Platelets are produced from the surface of megakaryocytes in the bone marrow, under tight homeostatic control regulated by the cytokine thrombopoietin. Platelets have a lifespan of approximately 7–10 days, and usually circulate in the blood stream in a quiescent state. Intact, undamaged vessel walls help to maintain platelets in this inactive state by releasing nitric oxide, which acts both to dilate the vessel wall and to inhibit platelet adhesion, activation, and aggregation. After trauma to the blood vessel wall, platelets are activated and, acting in concert with the endothelium and coagulation factors, form a stable clot. This chapter addresses platelet structure and function, and the response of platelets to vessel injury.
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Badimon, Lina, Felix C. Tanner, Giovanni G. Camici, and Gemma Vilahur. Pathophysiology of thrombosis. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198755777.003.0018.
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Ischaemic heart disease and stroke are major causes of death and morbidity worldwide. Coronary and cerebrovascular events are mainly a consequence of a sudden thrombotic occlusion of the vessel lumen. Arterial thrombosis usually develops on top of a disrupted atherosclerotic plaque because of the exposure of thrombogenic material, such as collagen fibrils and tissue factor (TF), to the flowing blood. TF, either expressed by subendothelial cells, macrophage- and/or vascular smooth muscle-derived foam-cells in atherosclerotic plaques, is a key element in the initiation of thrombosis due to its ability to induce thrombin formation (a potent platelet agonist) and subsequent fibrin deposition at sites of vascular injury. Adhered platelets at the site of injury also play a crucial role in the pathophysiology of atherothrombosis. Platelet surface receptors (mainly glycoproteins) interact with vascular structures and/or Von Willebrand factor triggering platelet activation signalling events, including an increase in intracellular free Ca2+, exposure of a pro-coagulant surface, and secretion of platelet granule content. On top of this, interaction between soluble agonists and platelet G-coupled protein receptors further amplifies the platelet activation response favouring integrin alpha(IIb)beta(3) activation, an essential step for platelet aggregation. Blood-borne TF and microparticles have also been shown to contribute to thrombus formation and propagation. As thrombus evolves different circulating cells (red-blood cells and leukocytes, along with occasional undifferentiated cells) get recruited in a timely dependent manner to the growing thrombus and further entrapped by the formation of a fibrin mesh.
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Levi, Marcel, and Tom van der Poll. Coagulation and the endothelium in acute injury in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0307.
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Vascular endothelial cells play a pivotal mediatory role in many responses to systemic inflammation, including the cross-talk between coagulation and inflammation in sepsis. Endothelial cells respond to the cytokines expressed and released by activated leukocytes, but can also release cytokines themselves. Furthermore, endothelial cells are able to express adhesion molecules and growth factors that may not only promote the inflammatory response further, but also affect a myriad of downstream responses. It has recently become clear that, in addition to these mostly indirect effects of the endothelium, injured endothelial cells directly interfere with platelet-vessel wall interactions, neutrophil entrapment through formation of extracellular nets, and activation of inflammation and coagulation mediated by microparticles. The role of the glycocalyx as an important interface between the endothelium and regulation of coagulation in inflammatory states has also gained a lot of recent attention.
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Badimon, Lina, and Gemma Vilahur. Atherosclerosis and thrombosis. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199687039.003.0040.
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Atherosclerosis is the main underlying cause of heart disease. The continuous exposure to cardiovascular risk factors induces endothelial activation/dysfunction which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. This results in the accumulation of lipids (low-density lipoprotein particles) in the extracellular matrix and the triggering of an inflammatory response. Accumulated low-density lipoprotein particles suffer modifications and become pro-atherogenic, enhancing leucocyte recruitment and further transmigration across the endothelium into the intima. Infiltrated monocytes differentiate into macrophages which acquire a specialized phenotypic polarization (protective or harmful), depending on the stage of the atherosclerosis progression. Once differentiated, macrophages upregulate pattern recognition receptors capable of engulfing modified low-density lipoprotein, leading to foam cell formation. Foam cells release growth factors and cytokines that promote vascular smooth muscle cell migration into the intima, which then internalize low-density lipoprotein via low-density lipoprotein receptor-related protein-1 receptors. As the plaque evolves, the number of vascular smooth muscle cells decline, whereas the presence of fragile/haemorrhagic neovessels increases, promoting plaque destabilization. Disruption of this atherosclerotic lesion exposes thrombogenic surfaces that initiate platelet adhesion, activation, and aggregation, as well as thrombin generation. Both lipid-laden vascular smooth muscle cells and macrophages release the procoagulant tissue factor, contributing to thrombus propagation. Platelets also participate in progenitor cell recruitment and drive the inflammatory response mediating the atherosclerosis progression. Recent data attribute to microparticles a potential modulatory effect in the overall atherothrombotic process. This chapter reviews our current understanding of the pathophysiological mechanisms involved in atherogenesis, highlights platelet contribution to thrombosis and atherosclerosis progression, and provides new insights into how atherothrombosis may be modulated.
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Badimon, Lina, and Gemma Vilahur. Atherosclerosis and thrombosis. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199687039.003.0040_update_001.
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Atherosclerosis is the main underlying cause of heart disease. The continuous exposure to cardiovascular risk factors induces endothelial activation/dysfunction which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. This results in the accumulation of lipids (low-density lipoprotein particles) in the intimal layer and the triggering of an inflammatory response. Accumulated low-density lipoprotein particles attached to the extracellular matrix suffer modifications and become pro-atherogenic, enhancing leucocyte recruitment and further transmigration across the endothelium into the intima. Infiltrated pro-atherogenic monocytes (mainly Mon2) differentiate into macrophages which acquire a specialized phenotypic polarization (protective/M1 or harmful/M2), depending on the stage of the atherosclerosis progression. Once differentiated, macrophages upregulate pattern recognition receptors capable of engulfing modified low-density lipoprotein, leading to foam cell formation. Foam cells release growth factors and cytokines that promote vascular smooth muscle cell migration into the intima, which then internalize low-density lipoproteins via low-density lipoprotein receptor-related protein-1 receptors becoming foam cells. As the plaque evolves, the number of vascular smooth muscle cells decline, whereas the presence of fragile/haemorrhagic neovessels and calcium deposits increases, promoting plaque destabilization. Disruption of this atherosclerotic lesion exposes thrombogenic surfaces rich in tissue factor that initiate platelet adhesion, activation, and aggregation, as well as thrombin generation. Platelets also participate in leucocyte and progenitor cell recruitment are likely to mediate atherosclerosis progression. Recent data attribute to microparticles a modulatory effect in the overall atherothrombotic process and evidence their potential use as systemic biomarkers of thrombus growth. This chapter reviews our current understanding of the pathophysiological mechanisms involved in atherogenesis, highlights platelet contribution to thrombosis and atherosclerosis progression, and provides new insights into how atherothrombosis may be prevented and modulated.
Book chapters on the topic "Platelet response"
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Lüscher, Ernst F. "Plasma Membrane Receptors and Platelet Response." In Platelet Membrane Glycoproteins. Springer US, 1985. http://dx.doi.org/10.1007/978-1-4684-4880-1_1.
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Sternberg, David, and Joshua Sonett. "Platelet Activation After Lung Transplantation." In Inflammatory Response in Cardiovascular Surgery. Springer London, 2013. http://dx.doi.org/10.1007/978-1-4471-4429-8_46.
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Wainwright, Cherry L., and James R. Parratt. "Platelet-derived Substances in Acute Myocardial Injury." In Myocardial Response to Acute Injury. Macmillan Education UK, 1992. http://dx.doi.org/10.1007/978-1-349-12522-7_9.
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Bevers, Edouard M., Paul Comfurius, and Robert F. A. Zwaal. "Mechanisms Involved in Platelet Procoagulant Response." In Advances in Experimental Medicine and Biology. Springer US, 1993. http://dx.doi.org/10.1007/978-1-4615-2994-1_15.
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Detwiler, Thomas C., Bernice M. Martin, and Richard D. Feinman. "Stimulus-Response Coupling in the Thrombin-Platelet Interaction." In Novartis Foundation Symposia. John Wiley & Sons, Ltd., 2008. http://dx.doi.org/10.1002/9780470720172.ch5.
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Shannon, Oonagh. "Determining Platelet Activation and Aggregation in Response to Bacteria." In Methods in Molecular Biology. Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-6673-8_17.
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Braquet, P., M. Paubert-Braquet, and M. Rola-Pleszczynski. "The Role of Platelet Activating Factor in the Immune Response." In Lipid Mediators in the Immunology of Shock. Springer US, 1987. http://dx.doi.org/10.1007/978-1-4613-0919-2_49.
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Kurachi, Michio, Kayoko Hongoh, Akiko Watanabe, and Hironaka Aihara. "Suppression of Bronchial Response to Platelet Activating Factor Following Taurine Administration." In Advances in Experimental Medicine and Biology. Springer US, 1987. http://dx.doi.org/10.1007/978-1-4899-0405-8_20.
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Smith, J. Bryan, Carol Dangelmaier, and Gerard Mauco. "Quantitation of Arachidonate Released during the Platelet Phosphatidylinositol Response to Thrombin." In Prostaglandins, Leukotrienes, and Lipoxins. Springer US, 1985. http://dx.doi.org/10.1007/978-1-4684-4946-4_20.
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Lapetina, Eduardo G., and Wolfgang Siess. "Platelet Response in Relation to Metabolism of Inositides and Protein Phosphorylation." In Calcium in Biological Systems. Springer US, 1985. http://dx.doi.org/10.1007/978-1-4613-2377-8_5.
Full textConference papers on the topic "Platelet response"
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Labow, R. S., E. Meek, G. A. Adams, and G. Rock. "AGGREGATION RESPONSE OF PLATELETS DURING INHIBITION OF PHOSPHOLIPASE A2." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644542.
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Arachidonic acid (AA) is liberated from platelet membrane phospholipids during stimulation and promotes cellular aggregation through the synthesis of thromboxane A2. Two pathways; phospholipase A2 (PLA2) or phospholipase C (PLC) followed by the action of acylglycerolipases, are thought to be activated during platelet stimulation and supply the necessary AA. We have reported that mono (2-ethylhexyl)phthalate (MEHP), a physiological metabolite of the plasticizer di(2-ethylhexyl)-phthalate (DEHP), commonly used in a variety of medical devices and storage containers, inhibits PLA2, but not PLC in platelet lysates. The effects of MEHP on intact platelets were studied. PLA2 activity in intact platelets or lysates was assayed by incubating them with 2-14C-arachidonyl-phosphatidylcholine and measuring formation of free 14C-arachidonic acid in 10 min. Platelet lysates hydrolyzed 10% of the substrate while 2.6% was hydrolyzed by intact platelets. The amount of MEHP needed to inhibit 14C-AA liberation was 0.35 mM for platelet lysates and 0.7 mM for intact platelets. Platelet aggregation induced by collagen was inhibited by MEHP (1 mM), although responses to adenosine diphosphate, AA and ionophore were unaffected. Identical effects on platelet aggregation were found when indomethacin (0.1 mM) was added. Higher concentrations of MEHP blocked platelet aggregation induced by adenosine diphosphate or AA but not ionophore or synergistic pairs of these stimuli, indicating a more generalized membrane disruption at higher MEHP concentrations. These results suggest that MEHP acts in a similar manner to indomethacin to block PLA2-mediated liberation of arachidonate during platelet aggregation(supported by MRC and NHRDP, Canada)
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Gentry, P. A., and G. S. Bondy. "The aggregation of bovine platelets is not dependent on thromboxane B2 production." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644500.
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Bovine and human platelets appear to be equally sensitive to inhibition by several environmental toxins even though the bovine is not generally recognised as a species prone to thromboembolic and hemorrhagic disease. During the examination of the mechanism of action of the toxins it became necessary to establish parameters for normal bovine platelet function.Bovine platelets suspended in homologous plasma demonstrate various responses to different agonists. Bovine platelets aggregate effectively and irreversibly to fibrillar form collagen and adenosine-diphosphate (ADP), undergo reversible aggregation in response to platelet activating factor (PAF), exhibit a minimal aggregation response to serotonin (5HT) and arachidonic acid (AA) and are refractory to acid-soluble collagen (calf skin). A synergistic aggregation response is observed with the combination of ADP and 5HT, an additive response with ADP and PAF, while the addition of AA has no effect on the ADP induced aggregation response. A biphasic response has not been observed with any of the agonists or with the combinations of agonists. There is no direct correlation between the maximum aggregation response induced by ADP and PAF and the amount of thromboxane B2 (TXB2) released from the stimulated platelets. Similarly when acetylsalicylic acid (ASA) is added to the platelet suspensions, TBXg release can be completely inhibited without any observable effect on the aggregation response. Platelet aggregation was also unaffected by indomethacin and dipyridamole. Verapamil is a weak inhibitor of ADP induced aggregation but is a potent inhibitor of PAF stimulated platelets. Bovine platelets appear to have some distinct characteristics since they exhibit some responses which are not only different from human platelets but are also different from platelets obtained from other large animals such as the sheep and horse.
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Okita, J. R., M. M. Frojmovic, S. Kristopeit, T. Wong, and T. J. Kunicki. "MONTREAL PLATELET SYNDROME: DECREASED ACTIVITY OF PLATELET CALPAINS ASSOCIATED WITH AGGREGATION ABNORMALITIES." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642822.
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The Montreal platelet syndrome (MPS) is an inherited disorder of platelet function characterized by a) severe thrombocytopenia, b) formation of "giant" platelets upon physical or biochemical stimulation, c) spontaneous aggregation (stir-induced microaggregate formation) and d) a lack of aggregation in response to thrombin. The Bernard-Soulier syndrome (BSS) is similar to MPS in that both syndromes are characterized by "giant" platelets and an abnormal aggregation response to thrombin. BSS patients have a deficiency of specific platelet glycoproteins (GPs). From our investigations we conclude MPS patients have apparently normal amounts of major platelet GPs. However, a defect in calpains (calcium-activated neutral proteinases) was detected in MPS platelets. The specific activity of calpains was decreased by 70% (p<0.001) in the cytosolic fraction of platelets from MPS patients as compared to that of platelets from normal control donors. The calpain activity of platelets from BSS patients was within the normal range.During the course of the biochemical studies, platelets from the MPS patients were shown to exhibit concurrent functional defects, i.e., stir-induced spontaneous aggregation and reduced to absent aggregation response to thrombin. It is concluded that MPS can be distinguished from BSS at the molecular level as follows: 1) MPS platelets contain normal amounts of GPs Ib, V and IX which are decreased or absent in BSS platelets; 2) The specific activity of calpains is reduced in MPS platelets but normal in BSS platelets. Supported by NIH (HL-33925, HL-32279), Amer. Heart Assoc. (85—GA—67, 83-186), Canadian Med. Res. Council (248-59) and Quebec Heart Fndn.
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Van Nueten, J. M., W. J. Janssens, and F. De Clerck. "VASOCONSTRICTION IN RESPONSE TO HUMAN PLATELET-VESSEL WALL INTERACTIONS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644598.
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Human blood platelets, stimulated with thrombin, induced contractions of isolated basilar artery segments of the dog. These platelet-mediated vascular contractions were inhibited in a concentration-dependent way by flunarizine, a Ca2+-entry blocker, selective for vascular tissues. This inhibition increased gradually as a function of time after contact with flunarizine to reach its maximum after 60-90 min. Biochemical and pharmacological analyses, using the 5-HT2-serotonergic antagonist ritanserin, the thromboxane A2/prostaglandin endo-peroxide antagonist BM 13.177 and the fatty acid cyclo-oxygenase inhibitor suprofen, showed that 5-hydroxytryptamine and prostanoids (thromboxane A2, prostaglandine endoperoxides) were the main mediators involved. They further suggested amplification between 5-hydroxytryptamine and prostanoids at the vascular level.(1) Incubation period; (2) Inhibition of platelet-mediated vascular contractions.This study demonstrates that 5-hydroxytryptamine, acting in concert with thromboxane A2 and/or prostaglandine-endoper-oxides, is responsible for the vasoconstrictor effects of aggregating platelets. It further indicates that influx of calcium ions is involved in these vasoconstrictor responses.
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Ware, J. A., B. A. Clark, M. Smith, and E. W. Salzman. "ABNORMALITIES OF CYTOPLASMIC [Ca++] IN PLATELETS FROM UREMIC PATIENTS STUDIED WITH AEQU0RIN AND INDO-1." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644748.
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Uremic patients have a hemorrhagic tendency, often with prolonged bleeding times and abnormalities of platelet function in vitro. Whether these defects result from plasma factors, abnormalities in platelet surface receptors, or intracellular mediators is unknown. Accordingly, blood was obtained from 16 patients with severe uremia (BUN >90), and platelets were washed, loaded with aequorin or indo-1, gel-filtered, and resuspended in either plasma or buffer. Of the 16 patients, 4 had template bleeding times greater than 12 minutes, but platelet aggregation in plasma was not consistently impaired. However, the rise in cytoplasmic [Ca++] in response to the Ca++-ionophore A23187 or ADP in aequorin-loaded platelets from the 4 patients with long bleeding times was much lower than in uremic patients with normal bleejljLng times or in normal volunteers. The reduced [Ca++] response was associated with decreased aggregation of gel-filtered platelets in buffer. Prolonged bleeding time was less consistently correlated with decreased responses to epinephrine or arachidonate. Suspending washed aequorin-loaded uremic platelets in normal plasma for 10-20 min did not reverse the decreased agonist-induced rise in [Ca++]; platelets from a normal donor resuspended in uremic pla^iya responded normally. The agonist-induced rise in [Ca++] shown by indo-1 was not abnormal in patients with prolonged bleeding times; however, uremic patients generally had higher indo-l-indicated basal platelet cytoplasmic [Ca++] than normal. We conclude that the hemorrhagic tendency in some patients with uremia (|s associated with abnormal intracellular platelet [Ca++] regulation marked by elevated resting [Ca++] and a decreased rise in cytoplasmic [Ca++] in response to certain agonists; this latter abnormality appears to be correlated with prolonged bleeding times.
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Joist, J. H., J. E. Bauman, and S. P. Sutera. "PLATELET ALTERATIONS IN RESPONSE TO REPETITIVE, SHORT-DURATION LAMINAR SHEAR STRESS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642843.
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We examined platelet aggregation (PAG = loss of single platelets), platelet dense granule release, and platelet injury (LDH loss) in normal human citrated platelet-rich plasma subjected to biologically more relevant repetitive, laminar shear stress of 25 and 50 dyn/cm2 in a computer-controlled cone-plate viscometer. Shear pulse duration (1-3 sec), shear pulse ramp function (rate of shear stress increase and decrease per pulse, 0.6-4 sec), number of shear pulses (1-20) and pauses between shear pulses (0-5 sec) were varied in different combinations to assess the effects of each variable on platelet alterations. Maximum PAG (92±8%) was observed with three 1 sec shear pulses, 0.6 sec ramp function and 1 sec between shear pause. PAG decreased with increasing ramp function, increasing number of shear pulses (>10), and increasing pause duration. Rapid platelet deaggregation (starting at 5 sec) was observed after a single 1 sec shear exposure. The rate of deaggregation decreased with increasing shear pulse number, increasing shear pulse amplitude, and increasing shear pulse duration. In contrast to PAG, dense granule release increased progressively with increasing shear pulse number, duration, and amplitude. No appreciable platelet injury (LDH loss) was observed under the conditions used. The findings indicate that massive reversible PAG can be induced by a single 1 sec shear pulse and that the extent of PAG with more prolonged, repetitive shear exposure is largely a function of platelet deaggregation rather than PAG. Thus, data previously reported from our laboratory and other investigators using prolonged (>5 sec) exposure of platelets to shear stress may require reevaluation.
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Wyler, B., and K. J. Clemetson. "THE ROLE OF GPIb IN PLATELET ACTIVATION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642922.
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Platelet membrane glycoprotein lb (GPIb) is known to contain a receptor for von Willebrand factor (vWf) and for thrombin. The role of GPIb in platelet activation was investigated by comparing the effect of removal of the binding sites by specific proteolysis with that of blocking them using specific antibodies. Specific removal of the 45 kDa outer part of GPIb by treatment of platelets with human leukocyte elastase caused loss of platelet agglutination response to von Willebrand factor (vWf) but also a weaker activation by thrombin similar to that found with Bernard-Soulier syndrome platelets which lack GPIb. Removal of the major part of the external region of the GPIba chain, including the 45 kDa domain, by calcium activated protease or by chymotrypsin, produced similar effects. The 45 kDa region of GPIba was purified by tryptic cleavage of isolated glycocalicin followed by gel filtration. Antibodies to this fragment were produced in rabbits and showed high specificity and affinity for the 45 kDa polypeptide. Fab fragments of IgG prepared from this anti serum affect platelet response to vWf and thrombin in a dose-dependent way. In both protease-treated and antibody-treated platelets the reduced response to thrombin, but not to vWf could be overcome by increasing the dose of thrombin. In contrast to removal of the 45 kDa domain, antibody treatment affected not only the platelet response to vWf and thrombin but also to collagen, ADP, PAF and arachidonic acid. Only the response to the calcium ionophore A23,187 was unaltered.Though not the essential receptor GPIb is clearly involved in platelet response to thrombin. A possible mechanism could involve a conformational change in the cytoplasmic/inter-membranous part of GPIb induced by binding of thrombin to the 45 kDa domain. Binding of antibodies might affect platelet activation by other agonists via a general down regulation effect. These results support the two receptor models for thrombin activation of platelets as proposed for other cell -types. In platelets the first receptor appears to be GPIb but the second receptor has not yet been identified.
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Gool, R. Van, C. P. M. Reutelingsperger, G. Hornstra, and H. C. Hemkera. "PLATELET FUNCTION IN PLASMA AT PHYSIOLOGICAL CALCIUM CONCENTRATION. THE USE OF VAC AS AN ANTICOAGULANT." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643764.
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We have purified from human placenta an anticoagulatory protein (VAC, Mr= 32,000), which inhibits phospholipid dependent procoagulant reactions through a calcium dependent high affinity binding to procoagulant phospholipids..When tested in citrated platelet rich plasma (cPRP), VAC does not affect platelet aggregation and secretion in reponse to ADP, collagen and thrombin. Purified VAC (0.05 μM, final concentration; f.c.) was used as an anticoagulant to prepare PRP (VAC-PRP). Platelet aggregation (optical density method) and release of newly absorbed 14C-sero-tonin (5HT) in response to adenosine diphospate (ADP) were measured and compared with platelet responses incPRP obtained simultaneously fromthe same donor.The response of ADP stimulated platelets in VAC-PRP differs strikingly from that in cPRP. In the latter, platelets react with a dose-dependent primary aggregation, followed by a thrombin (Ila)-independent second wave of aggregation associated with 5HT-secre-tion.Platelets in VAC-PRP, however, demonstratean increased primary aggregation in responseto ADP, which is followed by a IIa-mediated second wave of aggregation and 5HT-secretion.Increasing the VAC concentration does not affect the primary aggregation response, but delayed the IIa-dependent secondary events in a dose-dependent way. At 0.5 μ M VAC, platelets react to ADP (10 μM f.c.) with reversible aggregation only. No matter this high ADP-dose, secretion reaction does not occur. At this VAC concentration, epinephrine (5 μM f.c.) does not cause aggregation and 5HT-release at all, whereas incPRP both reactions occur quite readily. Although in VAC-PRP, epinephrine retains its synergistic effect on ADP to aggregate platelets, no 5HT release was ever observed and the resulting aggregation was alwaysreversible It is concluded that VAC is a suitable anticoagulant to investigate platelet function in the presence of physiological calcium concentration. Since platelet aggregation and release appear very different from results obtained in the usual way (cPRP, low calcium concentration) the physiological meaning of this latter method needs re-evaluation. Finally, our results cast severe doubt on epinephrine as an important platelet stimulant under physiological conditions.
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Melki, Imene, Nathalie Cloutier, Isabelle Allaeys, et al. "AI-05 Platelet response to immune complexes." In LUPUS 21ST CENTURY 2018 CONFERENCE, Abstracts of the Fourth Biannual Scientific Meeting of the North and South American and Caribbean Lupus Community, Armonk, New York, USA, September 13 – 15, 2018. Lupus Foundation of America, 2018. http://dx.doi.org/10.1136/lupus-2018-lsm.5.
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SANJAR, S., D. SMITH, J. MORLEY, L. MAZZONI, and C. TAPPARELLI. "PAF ANTAGONISM AND THE RESPONSE TO ALLERGEN." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644865.
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Intravenous infusion of platelet activating factor (PAF) causes platelets to aggregate and accumulate within the lung. A similar effect is observed when allergen is injected into sensitised animals. Since PAF is released in allergic reactions, it might be considered to be a mediator of this phenomenon. Intrathoracic accumulation of 111-Indium labelled platelets was detected by use of collimated sodium iodide crystal detectors as a part of an automated isotope monitoring system (AIMS 8000, Mumed ltd.). Intravenous infusion of PAF (600 ng/kg/h) caused progressive increase of the intrathoracic platelet content (TPC) (59%). Infusion of small doses of allergen (BGG, 300 ug/kg/h) produced comparable increase of TPC, whether animals were sensitised actively (1 mg/kg BGG+FCA i.p. and boosted two weeks later) (30%) or passively (i.v. injection of 0.25 ml anti-BGG serum) (53%) or received intravenous injections of preformed immune complexes. At a dose of 2 mg/kg/h, ginkgolide B (−5%) or kadsuranone (−1%) fully inhibited increased TPC in response to PAF. However, at higher doses (6 mg/kg/h) ginkgolide B did not diminish TPC in animals that were actively (33%) or passively (60%) sensitised, nor did kadsuranone (6 mg/kg/h) diminish the response in passively sensitised animals (42%) compared to vehicle animals (43%). These observations can be extended to acute bronchospasm and airway hyperreactivity which are secondary to platelet activation in these animals. It can be concluded that PAF formation appears to be a minor determinant of the acute response to allergen in the guinea-pig.
Reports on the topic "Platelet response"
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Thorbecke, G. J., and Zoltan Ovary. Effect of Adjuvants on Response to Pneumococcal Polysaccharide Injected Intraperitoneally. Platelet-Derived Immunoregulatory Activity. Defense Technical Information Center, 1985. http://dx.doi.org/10.21236/ada162996.
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