The Experts below are selected from a list of 267 Experts worldwide ranked by ideXlab platform
Neal S Kleiman - One of the best experts on this subject based on the ideXlab platform.
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role of reticulated Platelets and platelet size heterogeneity on platelet activity after dual antiplatelet therapy with aspirin and clopidogrel in patients with stable coronary artery disease
Journal of the American College of Cardiology, 2008Co-Authors: Sasidhar Guthikonda, Carlos L Alviar, Muthiah Vaduganathan, Mehmet E Arikan, Armando Tellez, Timothy Delao, Juan F Granada, Jing Fei Dong, Neal S KleimanAbstract:Objectives The aim of this study was to evaluate the relationship between reticulated Platelets (RPs), platelet size, and platelet function in patients with stable coronary artery disease (CAD) taking aspirin and clopidogrel. Background Reticulated Platelets are young Platelets that are larger and possibly more active than non-RPs. Methods Flow cytometry was used to measure RPs after staining with thiazole orange and to define the upper 20% and lower 20% of Platelets by size. Platelet aggregation was measured with light transmission aggregometry (LTA); platelet activation was assessed by measuring activated platelet surface expression of P-selectin and glycoprotein (GP) IIb/IIIa. Results Ninety patients were recruited and stratified into tertiles of %RPs. Patients in the upper tertile displayed greater platelet aggregation to 5-μmol/l adenosine diphosphate (ADP) (50.7 ± 16.4% vs. 34.2 ± 17.3%, p 20%) was higher in the upper tertile (53% vs. 17%, p 50%) was also elevated in the upper tertile (50% vs. 13%, p = 0.003). The larger platelet gate had a higher % of RPs compared with the smaller gate (15.4 ± 16.7% vs. 1.7 ± 2.3%, p Conclusions The proportion of circulating RPs strongly correlates with response to antiplatelet therapy in patients with stable CAD. Large Platelets exhibit increased reactivity despite dual antiplatelet therapy, compared with smaller Platelets.
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Platelets and platelet inhibitors in acute myocardial infarction
Cardiology Clinics, 1995Co-Authors: Suraj G. Kamat, Neal S KleimanAbstract:Platelets and platelet-rich thrombi play a pivotal role in the pathogenesis of acute myocardial infarction. A ruptured atherosclerotic plaque evokes a hemostatic response that is mediated by Platelets, its membrane receptors, adhesive ligands, the presence or generation of platelet agonists, and the activation of the coagulation cascade with fibrin generation. The interaction of Platelets with the coagulation and the fibrinolytic systems is complex; new and exciting developments, however, in the ability to pharmacologically control platelet responses during thrombolysis in acute myocardial infarction will enhance our understanding of these interactions and will eventually translate into clinical benefit.
Alan D. Michelson - One of the best experts on this subject based on the ideXlab platform.
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Flow cytometry
Platelets, 2012Co-Authors: Michelle A. Berny-lang, A.l. Frelinger Iii, Alan D. MichelsonAbstract:Platelets is the definitive current source of state-of-the-art knowledge about Platelets and covers the entire field of platelet biology, pathophysiology, and clinical medicine. Recently there has been a rapid expansion of knowledge in both basic biology and the clinical approach to platelet-related diseases including thrombosis and hemorrhage. Novel platelet function tests, drugs, blood bank storage methods, and gene therapies have been incorporated into patient care or are in development. This book draws all this information into a single, comprehensive and authoritative resource.Comprehensive and definitive source of knowledge about Platelets for clinicians, pathologists and scientists Integrates the entire field of platelet biology, pathophysiology, and clinical medicine Full color reference comprising 64 chapters, 1400 pages, and 16,000 references Contributions from 126 world leaders in their fields New chapters on topics such as the regulation of platelet life span, platelet microRNAs, GPVI and CLEC-2, monitoring of antiplatelet therapy, novel antiplatelet therapy, and making Platelets ex vivo
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Flow cytometry
Platelets, 2011Co-Authors: Alan D. Michelson, Md Linden, Mr Barnard, Mi Furman, A. L. FrelingerAbstract:Platelets is the definitive current source of state-of-the-art knowledge about Platelets and covers the entire field of platelet biology, pathophysiology, and clinical medicine. Recently there has been a rapid expansion of knowledge in both basic biology and the clinical approach to platelet-related diseases including thrombosis and hemorrhage. Novel platelet function tests, drugs, blood bank storage methods, and gene therapies have been incorporated into patient care or are in development. This book draws all this information into a single, comprehensive and authoritative resource.· First edition won Best Book in Medical Science Award from the Association of American Publishers· Contains fourteen new chapters on topics such as platelet genomics and proteomics, inhibition of platelet function by the endothelium, clinical tests of platelet function, real time in vivo imaging of Platelets, and inherited thrombocytopenias· A comprehensive full color reference comprising over 70 chapters, 1400 pages, and 16,000 references
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Evaluation of platelet function by flow cytometry
Methods, 2000Co-Authors: Alan D. Michelson, Marc R. Barnard, Lori A. Krueger, A. L. Frelinger, Mark I. FurmanAbstract:Platelet function in whole blood can be comprehensively evaluated by flow cytometry. Flow cytometry can be used to measure platelet reactivity, circulating activated Platelets, platelet-platelet aggregates, leukocyte-platelet aggregates, procoagulant platelet-derived microparticles, and calcium flux. Clinical applications of whole blood flow cytometric assays of platelet function in disease states (e.g., acute coronary syndromes, angioplasty, and stroke) may include identification of patients who would benefit from additional antiplatelet therapy and prediction of ischemic events. Circulating monocyte-platelet aggregates appear to be a more sensitive marker of in vivo platelet activation than circulating P-selectin-positive Platelets. Flow cytometry can also be used in the following clinical settings: monitoring of GPIIb-IIIa antagonist therapy, diagnosis of inherited deficiencies of platelet surface glycoproteins, diagnosis of storage pool disease, diagnosis of heparin-induced thrombocytopenia, and measurement of the rate of thrombopoiesis. © 2000 Academic Press.
Asru K. Sinha - One of the best experts on this subject based on the ideXlab platform.
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Isolation and study of insulin activated nitric oxide synthase inhibitory protein in acute myocardial infarction subjects
Journal of Thrombosis and Thrombolysis, 2012Co-Authors: Gausal. A. Khan, Kushal Chakraborty, Shyamali Basuroy, Sharmistha Chakraborty Patra, Gannareddy Girish, G. Bhattacharya, Asru K. SinhaAbstract:Insulin inhibits platelet aggregation through nitric oxide synthesis by stimulating platelet insulin activated nitric oxide synthase. Impaired platelet insulin activated nitric oxide synthase in acute myocardial infarction (AMI) patients had been reported and thus our aim was to identify and isolate the factors impairing insulin activated nitric oxide in acute myocardial infarction patients’ plasma and study its effect on Platelets aggregation in vitro. The insulin activated nitric oxide synthase inhibitor was identified as a protein and was purified from the plasma of AMI subjects using DEAE cellulose and Sephadex G-50 column, molecular weight determined by SDS-PAGE, nitric oxide quantified by methaemoglobin method, inhibitor protein quantified in plasma by immunoblot and ELISA, platelet aggregation studies done using an aggregometer, thromboxane-A2 in the Platelets determined by radioimmunoassay, ^125I-insulin radioligand binding studies done using normal subject Platelets. The purified nitric oxide synthase inhibitor protein was ~66 kDa, concentration in AMI subjects’ plasma varied from 114 to 9,090 μM and was undetected in normal subjects’ plasma. The inhibitor protein competes with insulin for insulin receptor binding sites. The Incubation of the normal subject PRP with 5.0 μM inhibitor for 30 min followed by 0.4 μM ADP addition caused platelet aggregation in vitro, 130 μM aspirin or 400 μU insulin/ml addition was able to abrogate 0.4 μM ADP induced platelet aggregation even in the presence of 5.0 μM inhibitor. A potent inhibitory protein against insulin activated nitric oxide synthase in Platelets appears in circulation of AMI subjects impairing nitric oxide production, potentiating ADP induced platelet aggregation and increasing the thromboxane-A2 level in Platelets.
Joseph E. Italiano - One of the best experts on this subject based on the ideXlab platform.
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Anti-Coagulation Agents Provide a Mechanism to Inhibit Tumor Cells From Hijacking the Angiogenic Potential of Platelets
Blood, 2011Co-Authors: Elisabeth M. Battinelli, Beth A. Markens, Joseph E. ItalianoAbstract:Abstract 1149 While an association between cancer and Platelets has been long recognized, the cause and effect relationship linking the two remains unclear. Provocatively, recent studies suggest that anti-platelet agents can increase overall survival and decrease metastatic disease in cancer patients. Because angiogenesis is crucial for tumor growth beyond 1–2 mm 3 , one view is that Platelets may regulate new blood vessel growth through release of the vast array of angiogenesis promoters and stimulators stored in platelet alpha granules. We previously demonstrated that physiological agonists as well as tumor cells (MCF-7 breast cancer cells) could direct the preferential release of pro-angiogenic regulatory proteins from Platelets, providing a mechanism for how tumor cells may promote new blood vessel growth in the tumor microenvironment (Battinelli et. al Blood, 2011). In line with these observations, we recently showed that the pro-angiogenic potential of Platelets could be attenuated by the anti-platelet agent aspirin providing one mechanism by which platelet inhibitors may attenuate metastatic spread. These observations motivated the hypothesis that agents with anti-thrombotic effects, including LMWH, may also alter the release of angiogenesis regulatory proteins from Platelets. Our results reveal that Platelets pretreated with daltaparin (a LMWH) showed significant decreases in the amount of VEGF released in response to activation by either the platelet agonist ADP (0.633+/−0.63 with dalteparin vs. 55.71+/−13.92 without dalteparin, p Disclosures: No relevant conflicts of interest to declare.
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Mechanics of proplatelet elaboration
Journal of Thrombosis and Haemostasis, 2007Co-Authors: Joseph E. Italiano, S. Patel-hett, J. H. HartwigAbstract:The cellular and molecular basis of the intricate process by which megakaryocytes (MKs) form and release Platelets remains poorly understood. Work has shown that proPlatelets, long cytoplasmic extensions made by mature MKs, are essential intermediates in platelet biogenesis. Microtubules are the main structural component of proPlatelets and it is microtubule sliding, driven by dynein motors within cortical bundles, which elongates and thins proPlatelets. Kinesin motors carry their cargo of platelet-specific granules and organelles into the proPlatelets using the microtubule bundles as tracks. Extension of proPlatelets is associated with repeated actin-dependent bending and bifurcation, which results in considerable amplification of free proplatelet ends. Large proPlatelets, dissociated from the residual MK cell body, have the capacity to mature Platelets. Only the ends of proPlatelets form marginal microtubule coils similar to that observed in mature Platelets, demonstrating that platelet formation completes primarily at proplatelet ends. Understanding the molecular basis of platelet formation requires detailed knowledge of how the MK microtubule machinery interacts to generate proPlatelets and release Platelets.
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The biogenesis of Platelets from megakaryocyte proPlatelets
Journal of Clinical Investigation, 2005Co-Authors: Sunita R. Patel, J. H. Hartwig, Joseph E. ItalianoAbstract:Platelets are formed and released into the bloodstream by precursor cells called megakaryocytes that reside within the bone marrow. The production of Platelets by megakaryocytes requires an intricate series of remodeling events that result in the release of thousands of Platelets from a single megakaryocyte. Abnormalities in this process can result in clinically significant disorders. Thrombocytopenia (platelet counts less than 150,000/microl) can lead to inadequate clot formation and increased risk of bleeding, while thrombocythemia (platelet counts greater than 600,000/microl) can heighten the risk for thrombotic events, including stroke, peripheral ischemia, and myocardial infarction. This Review will describe the process of platelet assembly in detail and discuss several disorders that affect platelet production.
Perumal Thiagarajan - One of the best experts on this subject based on the ideXlab platform.
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Sulfatides Activate Platelets Through P-Selectin and Enhance Platelet and Platelet–Leukocyte Aggregation
Arteriosclerosis Thrombosis and Vascular Biology, 2004Co-Authors: Michael Merten, C. Beythien, Kai Gutensohn, P. Kühnl, Thomas Meinertz, Perumal ThiagarajanAbstract:Objective— Sulfatides are sulfated glycosphingolipids present on the surface of a variety of cells; however, their exact physiological function is not known. Recently, we have shown that the inhibition of sulfatide–P-selectin interactions leads to disaggregation of platelet aggregates. Methods and Results— In this study, we show that sulfatides activated Platelets as they increased activation of GPIIb/IIIa (PAC-1 epitope) and expression of P-selectin on the platelet surface. Furthermore, sulfatides aggregated washed Platelets in a dose-dependent manner and enhanced platelet aggregation in platelet-rich plasma. Previous activation of Platelets was necessary for this effect. Monoclonal anti–P-selectin antibodies inhibited not only sulfatide-induced PAC-1 binding to Platelets but also sulfatide-induced platelet aggregation, suggesting that sulfatides activate platelet GPIIb/IIIa via signaling through P-selectin. The proaggegatory effect of sulfatides was also observed in an ex vivo thrombosis model using whole blood and pulsatile flow at 37°C. In this model, sulfatides significantly enhanced platelet aggregation and the formation of platelet–leukocyte aggregates. Conclusions— We show that sulfatide-P-selectin interactions lead to subsequent platelet activation and P-selectin expression, forming a positive feedback loop that can potentiate formation of stable platelet aggregates. In addition, sulfatides enhance the aggregation of platelet–leukocyte aggregates. These mechanisms may play a significant role in hemostasis and thrombosis.
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collagen induced exposure of anionic phospholipid in Platelets and platelet derived microparticles
Journal of Biological Chemistry, 1991Co-Authors: Perumal Thiagarajan, Jonathan F TaitAbstract:Abstract We have shown recently that the calcium-dependent phospholipid-binding protein annexin V (placental anticoagulant protein I) can be used to study the exposure of anionic phospholipid after platelet activation. In this study we have further examined the mechanism of this process. Collagen-induced exposure of annexin V binding sites correlated directly with increased ability to support activity of the reconstituted prothrombinase complex. The potency of annexin V as an inhibitor of platelet prothrombinase was the same as its Kd for Platelets. Prior incubation of Platelets with 5'-p-fluorosulfonylbenzoyladenosine or p-chloromercuribenzenesulfonate had no significant effect on annexin V binding. Similarly, inhibition of platelet cyclic endoperoxide synthesis by acetylsalicylic acid or indomethacin did not inhibit annexin V binding. Staurosporine inhibited collagen-induced, but not A23187-induced, annexin V binding. Agents that increase intraplatelet cyclic nucleotides partially inhibited collagen-induced annexin V binding. Thus, collagen-induced exposure of anionic phospholipid appears to depend primarily on increases in intraplatelet free calcium and may be independent of ADP- or endoperoxide-mediated pathways. Binding sites for annexin V on microparticles derived from collagen-stimulated Platelets were demonstrated by flow cytometry and gel filtration. In addition, prior incubation of Platelets with 100 nM annexin V inhibited factor Va binding to both Platelets and platelet-derived microparticles. These results support the concept that the procoagulant effect of Platelets and platelet-derived microparticles is mediated by calcium-induced exposure of anionic phospholipids.