Platelet Activation: A series of progressive, overlapping events, triggered by exposure of the PLATELETS to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.Thromboxane A2: An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).Platelet Aggregation: The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.Receptors, Thromboxane: Cell surface proteins that bind THROMBOXANES with high affinity and trigger intracellular changes influencing the behavior of cells. Some thromboxane receptors act via the inositol phosphate and diacylglycerol second messenger systems.Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase.Receptors, Thromboxane A2, Prostaglandin H2: A subclass of eicosanoid receptors that have specificity for THROMBOXANE A2 and PROSTAGLANDIN H2.Thromboxane B2: A stable, physiologically active compound formed in vivo from the prostaglandin endoperoxides. It is important in the platelet-release reaction (release of ADP and serotonin).Prostaglandins H: A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. The most frequently encountered member of this group is the prostaglandin H2.Thromboxane-A Synthase: An enzyme found predominantly in platelet microsomes. It catalyzes the conversion of PGG(2) and PGH(2) (prostaglandin endoperoxides) to thromboxane A2. EC 5.3.99.5.Prostaglandin Endoperoxides, Synthetic: Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds.Platelet Count: The number of PLATELETS per unit volume in a sample of venous BLOOD.Platelet Adhesiveness: The process whereby PLATELETS adhere to something other than platelets, e.g., COLLAGEN; BASEMENT MEMBRANE; MICROFIBRILS; or other "foreign" surfaces.15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid: A stable prostaglandin endoperoxide analog which serves as a thromboxane mimetic. Its actions include mimicking the hydro-osmotic effect of VASOPRESSIN and activation of TYPE C PHOSPHOLIPASES. (From J Pharmacol Exp Ther 1983;224(1): 108-117; Biochem J 1984;222(1):103-110)Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)Platelet Membrane Glycoproteins: Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.Prostaglandin H2: A cyclic endoperoxide intermediate produced by the action of CYCLOOXYGENASE on ARACHIDONIC ACID. It is further converted by a series of specific enzymes to the series 2 prostaglandins.Receptors, Prostaglandin: Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.6-Ketoprostaglandin F1 alpha: The physiologically active and stable hydrolysis product of EPOPROSTENOL. Found in nearly all mammalian tissue.Platelet Factor 4: A CXC chemokine that is found in the alpha granules of PLATELETS. The protein has a molecular size of 7800 kDa and can occur as a monomer, a dimer or a tetramer depending upon its concentration in solution. Platelet factor 4 has a high affinity for HEPARIN and is often found complexed with GLYCOPROTEINS such as PROTEIN C.Prostanoic Acids: 2-Octylcyclopentaneheptanoic acids. The family of saturated carbon-20 cyclic fatty acids that represent the parent compounds of the prostaglandins.Thrombin: An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.P-Selectin: Cell adhesion molecule and CD antigen that mediates the adhesion of neutrophils and monocytes to activated platelets and endothelial cells.Platelet Glycoprotein GPIIb-IIIa Complex: Platelet membrane glycoprotein complex important for platelet adhesion and aggregation. It is an integrin complex containing INTEGRIN ALPHAIIB and INTEGRIN BETA3 which recognizes the arginine-glycine-aspartic acid (RGD) sequence present on several adhesive proteins. As such, it is a receptor for FIBRINOGEN; VON WILLEBRAND FACTOR; FIBRONECTIN; VITRONECTIN; and THROMBOSPONDINS. A deficiency of GPIIb-IIIa results in GLANZMANN THROMBASTHENIA.Platelet Aggregation Inhibitors: Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.Platelet Glycoprotein GPIb-IX Complex: Platelet membrane glycoprotein complex essential for normal platelet adhesion and clot formation at sites of vascular injury. It is composed of three polypeptides, GPIb alpha, GPIb beta, and GPIX. Glycoprotein Ib functions as a receptor for von Willebrand factor and for thrombin. Congenital deficiency of the GPIb-IX complex results in Bernard-Soulier syndrome. The platelet glycoprotein GPV associates with GPIb-IX and is also absent in Bernard-Soulier syndrome.Arachidonic AcidsAdenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.Platelet Function Tests: Laboratory examination used to monitor and evaluate platelet function in a patient's blood.Platelet Transfusion: The transfer of blood platelets from a donor to a recipient or reinfusion to the donor.Platelet Activating Factor: A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.Bleeding Time: Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function.Thrombosis: Formation and development of a thrombus or blood clot in the blood vessel.beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, pre-eclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders.Membranes: Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures.Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation.Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.Intracellular Membranes: Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.Receptors, Purinergic P2Y12: A subclass of purinergic P2Y receptors that have a preference for ADP binding and are coupled to GTP-BINDING PROTEIN ALPHA SUBUNIT, GI. The P2Y12 purinergic receptors are found in PLATELETS where they play an important role regulating PLATELET ACTIVATION.Epoprostenol: A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).Thrombocytopenia: A subnormal level of BLOOD PLATELETS.von Willebrand Factor: A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in VON WILLEBRAND DISEASES is due to the deficiency of this factor.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).HydrazinesPlatelet Membrane Glycoprotein IIb: Platelet membrane glycoprotein IIb is an integrin alpha subunit that heterodimerizes with INTEGRIN BETA3 to form PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX. It is synthesized as a single polypeptide chain which is then postranslationally cleaved and processed into two disulfide-linked subunits of approximately 18 and 110 kDa in size.Blood Coagulation: The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot.Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Erythrocyte Membrane: The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.Megakaryocytes: Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Membranes, Artificial: Artificially produced membranes, such as semipermeable membranes used in artificial kidney dialysis (RENAL DIALYSIS), monomolecular and bimolecular membranes used as models to simulate biological CELL MEMBRANES. These membranes are also used in the process of GUIDED TISSUE REGENERATION.Antigens, Human Platelet: Human alloantigens expressed only on platelets, specifically on platelet membrane glycoproteins. These platelet-specific antigens are immunogenic and can result in pathological reactions to transfusion therapy.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Hemostasis: The process which spontaneously arrests the flow of BLOOD from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements (eg. ERYTHROCYTE AGGREGATION), and the process of BLOOD COAGULATION.Membrane Fluidity: The motion of phospholipid molecules within the lipid bilayer, dependent on the classes of phospholipids present, their fatty acid composition and degree of unsaturation of the acyl chains, the cholesterol concentration, and temperature.Prostaglandin Endoperoxides: Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc.Receptors, Thrombin: A family of proteinase-activated receptors that are specific for THROMBIN. They are found primarily on PLATELETS and on ENDOTHELIAL CELLS. Activation of thrombin receptors occurs through the proteolytic action of THROMBIN, which cleaves the N-terminal peptide from the receptor to reveal a new N-terminal peptide that is a cryptic ligand for the receptor. The receptors signal through HETEROTRIMERIC GTP-BINDING PROTEINS. Small synthetic peptides that contain the unmasked N-terminal peptide sequence can also activate the receptor in the absence of proteolytic activity.Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Cytoplasmic Granules: Condensed areas of cellular material that may be bounded by a membrane.Kinetics: The rate dynamics in chemical or physical systems.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Apyrase: A calcium-activated enzyme that catalyzes the hydrolysis of ATP to yield AMP and orthophosphate. It can also act on ADP and other nucleoside triphosphates and diphosphates. EC 3.6.1.5.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Antigens, CD63: Ubiquitously-expressed tetraspanin proteins that are found in late ENDOSOMES and LYSOSOMES and have been implicated in intracellular transport of proteins.Crotalid Venoms: Venoms from snakes of the subfamily Crotalinae or pit vipers, found mostly in the Americas. They include the rattlesnake, cottonmouth, fer-de-lance, bushmaster, and American copperhead. Their venoms contain nontoxic proteins, cardio-, hemo-, cyto-, and neurotoxins, and many enzymes, especially phospholipases A. Many of the toxins have been characterized.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Dual Specificity Phosphatase 2: A dual specificity phosphatase subtype that plays a role in intracellular signal transduction by inactivating MITOGEN-ACTIVATED PROTEIN KINASES. It has specificity for EXTRACELLULAR SIGNAL-REGULATED MAP KINASES and is primarily localized to the CELL NUCLEUS.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.Platelet Factor 3: A phospholipid from the platelet membrane that contributes to the blood clotting cascade by forming a phospholipid-protein complex (THROMBOPLASTIN) which serves as a cofactor with FACTOR VIIA to activate FACTOR X in the extrinsic pathway of BLOOD COAGULATION.Blood Proteins: Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.Basement Membrane: A darkly stained mat-like EXTRACELLULAR MATRIX (ECM) that separates cell layers, such as EPITHELIUM from ENDOTHELIUM or a layer of CONNECTIVE TISSUE. The ECM layer that supports an overlying EPITHELIUM or ENDOTHELIUM is called basal lamina. Basement membrane (BM) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. BM, composed mainly of TYPE IV COLLAGEN; glycoprotein LAMININ; and PROTEOGLYCAN, provides barriers as well as channels between interacting cell layers.Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro.Thrombasthenia: A congenital bleeding disorder with prolonged bleeding time, absence of aggregation of platelets in response to most agents, especially ADP, and impaired or absent clot retraction. Platelet membranes are deficient in or have a defect in the glycoprotein IIb-IIIa complex (PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX).Cell Line: Established cell cultures that have the potential to propagate indefinitely.Receptor, PAR-1: A thrombin receptor subtype that couples to HETEROTRIMERIC GTP-BINDING PROTEINS resulting in the activation of a variety of signaling mechanisms including decreased intracellular CYCLIC AMP, increased TYPE C PHOSPHOLIPASES and increased PHOSPHOLIPASE A2.Receptors, Collagen: Collagen receptors are cell surface receptors that modulate signal transduction between cells and the EXTRACELLULAR MATRIX. They are found in many cell types and are involved in the maintenance and regulation of cell shape and behavior, including PLATELET ACTIVATION and aggregation, through many different signaling pathways and differences in their affinities for collagen isoforms. Collagen receptors include discoidin domain receptors, INTEGRINS, and glycoprotein VI.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Epinephrine: The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.Immunoglobulin Fab Fragments: Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Calcimycin: An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.Receptors, Purinergic P2Y1: A subclass of purinergic P2Y receptors that have a preference for ATP and ADP. The activated P2Y1 receptor signals through the G-PROTEIN-coupled activation of PHOSPHOLIPASE C and mobilization of intracellular CALCIUM.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Molecular Weight: The sum of the weight of all the atoms in a molecule.Pentanoic AcidsProstaglandin-Endoperoxide Synthases: Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Heparin: A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Platelet Storage Pool Deficiency: Disorder characterized by a decrease or lack of platelet dense bodies in which the releasable pool of adenine nucleotides and 5HT are normally stored.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Platelet-Rich Plasma: A preparation consisting of PLATELETS concentrated in a limited volume of PLASMA. This is used in various surgical tissue regeneration procedures where the GROWTH FACTORS in the platelets enhance wound healing and regeneration.Eicosanoids: A class of compounds named after and generally derived from C20 fatty acids (EICOSANOIC ACIDS) that includes PROSTAGLANDINS; LEUKOTRIENES; THROMBOXANES, and HYDROXYEICOSATETRAENOIC ACIDS. They have hormone-like effects mediated by specialized receptors (RECEPTORS, EICOSANOID).Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Cyclooxygenase 1: A constitutively-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes.Cell Adhesion: Adherence of cells to surfaces or to other cells.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Phosphatidylinositols: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Leukocytes: White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process.Oligopeptides: Peptides composed of between two and twelve amino acids.Hemorheology: The deformation and flow behavior of BLOOD and its elements i.e., PLASMA; ERYTHROCYTES; WHITE BLOOD CELLS; and BLOOD PLATELETS.Bernard-Soulier Syndrome: A familial coagulation disorder characterized by a prolonged bleeding time, unusually large platelets, and impaired prothrombin consumption.Vasoconstrictor Agents: Drugs used to cause constriction of the blood vessels.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Thrombopoietin: A humoral factor that stimulates the production of thrombocytes (BLOOD PLATELETS). Thrombopoietin stimulates the proliferation of bone marrow MEGAKARYOCYTES and their release of blood platelets. The process is called THROMBOPOIESIS.Dinoprost: A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions.Phosphatidic Acids: Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Thrombopoiesis: The process of generating thrombocytes (BLOOD PLATELETS) from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW via the MEGAKARYOCYTES. The humoral factor with thrombopoiesis-stimulating activity is designated THROMBOPOIETIN.Microscopy, Electron, Scanning: Microscopy in which the object is examined directly by an electron beam scanning the specimen point-by-point. The image is constructed by detecting the products of specimen interactions that are projected above the plane of the sample, such as backscattered electrons. Although SCANNING TRANSMISSION ELECTRON MICROSCOPY also scans the specimen point by point with the electron beam, the image is constructed by detecting the electrons, or their interaction products that are transmitted through the sample plane, so that is a form of TRANSMISSION ELECTRON MICROSCOPY.Phosphatidylserines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.Mice, Inbred C57BLEnzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Microfilament Proteins: Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell.Edetic Acid: A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Membrane Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.Thrombocytosis: Increased numbers of platelets in the peripheral blood. (Dorland, 27th ed)Purinergic P2Y Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2Y RECEPTORS. Included under this heading are antagonists for specific P2Y receptor subtypes.Hirudins: Single-chain polypeptides of about 65 amino acids (7 kDa) from LEECHES that have a neutral hydrophobic N terminus, an acidic hydrophilic C terminus, and a compact, hydrophobic core region. Recombinant hirudins lack tyr-63 sulfation and are referred to as 'desulfato-hirudins'. They form a stable non-covalent complex with ALPHA-THROMBIN, thereby abolishing its ability to cleave FIBRINOGEN.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Purpura, Thrombocytopenic: Any form of purpura in which the PLATELET COUNT is decreased. Many forms are thought to be caused by immunological mechanisms.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Methacrylates: Acrylic acids or acrylates which are substituted in the C-2 position with a methyl group.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Prostaglandins, Synthetic: Compounds obtained by chemical synthesis that are analogs or derivatives of naturally occurring prostaglandins and that have similar activity.Blood Cell Count: The number of LEUKOCYTES and ERYTHROCYTES per unit volume in a sample of venous BLOOD. A complete blood count (CBC) also includes measurement of the HEMOGLOBIN; HEMATOCRIT; and ERYTHROCYTE INDICES.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Prostaglandins E: (11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.CD40 Ligand: A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.PhosphoproteinsIntegrin alpha2beta1: An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Blood Preservation: The process by which blood or its components are kept viable outside of the organism from which they are derived (i.e., kept from decay by means of a chemical agent, cooling, or a fluid substitute that mimics the natural state within the organism).Receptors, Purinergic P2: A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.Fibrin: A protein derived from FIBRINOGEN in the presence of THROMBIN, which forms part of the blood clot.Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.Fibrinolytic Agents: Fibrinolysin or agents that convert plasminogen to FIBRINOLYSIN.Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.Cell Size: The quantity of volume or surface area of CELLS.Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)Solubility: The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Receptors, Fibrinogen: Receptors that bind FIBRINOGEN through distinct adhesive sequences on the fibrinogen molecule. Although MACROPHAGE-1 ANTIGEN is considered an important signaling molecule for fibrinogen interaction, a variety of INTEGRINS from all three major families, (beta1, beta2, and beta3) have been shown to bind fibrinogen.Phospholipases A: Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Blood Coagulation Disorders: Hemorrhagic and thrombotic disorders that occur as a consequence of abnormalities in blood coagulation due to a variety of factors such as COAGULATION PROTEIN DISORDERS; BLOOD PLATELET DISORDERS; BLOOD PROTEIN DISORDERS or nutritional conditions.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Antigens, CD36: Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS.Thrombospondins: A family of related, adhesive glycoproteins which are synthesized, secreted, and incorporated into the extracellular matrix of a variety of cells, including alpha granules of platelets following thrombin activation and endothelial cells. They interact with a number of BLOOD COAGULATION FACTORS and anticoagulant factors. Five distinct forms have been identified, thrombospondin 1, -2, -3, -4, and cartilage oligomeric matrix protein (COMP). They are involved in cell adhesion, platelet aggregation, cell proliferation, angiogenesis, tumor metastasis, VASCULAR SMOOTH MUSCLE growth, and tissue repair.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Fluorescent Dyes: Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.Receptors, IgG: Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).Thromboplastin: Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation.BenzoxepinsStress, Mechanical: A purely physical condition which exists within any material because of strain or deformation by external forces or by non-uniform thermal expansion; expressed quantitatively in units of force per unit area.Octoxynol: Nonionic surfactant mixtures varying in the number of repeating ethoxy (oxy-1,2-ethanediyl) groups. They are used as detergents, emulsifiers, wetting agents, defoaming agents, etc. Octoxynol-9, the compound with 9 repeating ethoxy groups, is a spermatocide.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.Hemorrhage: Bleeding or escape of blood from a vessel.Phospholipases A2: Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES.Vasoconstriction: The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.Anticoagulants: Agents that prevent clotting.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).

*Thromboxane

... stimulating activation of new platelets as well as increasing platelet aggregation. Platelet aggregation is achieved by ... mediating expression of the glycoprotein complex GP IIb/IIIa in the cell membrane of platelets. Circulating fibrinogen binds ... The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ... Thromboxane is named for its role in clot formation (thrombosis). Thromboxane-A synthase, an enzyme found in platelets, ...

*Thromboxane A2

This is achieved by increasing expression of the glycoprotein complex GPIIb/IIIa on the cell membrane of platelets. The same ... it stimulates activation of new platelets as well as increases platelet aggregation. ... Thromboxane A2 (TXA2) is a type of thromboxane that is produced by activated platelets and has prothrombotic properties: ... "Thromboxane A2-induced contraction of rat caudal arterial smooth muscle involves activation of Ca2+ entry and Ca2+sensitization ...

*Platelet

Platelets secrete thromboxane A2, which acts on the platelet's own thromboxane receptors on the platelet surface (hence the so- ... Platelet activation causes its membrane surface to become negatively charged. One of the signaling pathways turns on scramblase ... 2007). "Programmed anuclear cell death delimits platelet life span". Cell. 128 (6): 1173-86. doi:10.1016/j.cell.2007.01.037. ... The platelet-rich plasma (PRP) is removed from the red cells, then centrifuged at a faster setting to harvest the platelets ...

*Low-density lipoprotein receptor-related protein 8

It is involved with cell-to-cell communication and migration of neurons, and causes the activation of Dab1. F-spondin is a ... Thromboxane A2 functions to activate more platelets, and this leads to a greater chance for blood clots to form. There is also ... and platelets. ApoER2 is thought to play a key role in the process of platelet binding. β2GPI has the proper binding site for ... ApoE binding leads to the cleavage of ApoER2 into secreted proteins by the actions of the plasma membrane protein gamma ...

*GNAQ

"Platelet signal transduction defect with Galpha subunit dysfunction and diminished Galphaq in a patient with abnormal platelet ... Activation is terminated by a GTPase intrinsic to the G-alpha subunit. G-alpha-q is the alpha subunit of one of the ... Cell. Biochem. 144 (1): 45-51. doi:10.1007/BF00926739. PMID 7791744. Allgeier A, Offermanns S, Van Sande J, Spicher K, Schultz ... Johnson GJ, Leis LA, Dunlop PC (1996). "Specificity of G alpha q and G alpha 11 gene expression in platelets and erythrocytes. ...

*Fatty acid metabolism

Conversely, thromboxanes (produced by platelet cells) are vasoconstrictors and facilitate platelet aggregation. Their name ... and the activation of protein kinase C (PKC), which is then translocated from the cell cytoplasm to the cell membrane. Although ... Prostacyclins are powerful locally acting vasodilators and inhibit the aggregation of blood platelets. Through their role in ... All cells in the body need to manufacture and maintain their membranes and the membranes of their organelles. Whether they rely ...

*GNA13

Offermanns S, Hu YH, Simon MI (Oct 1996). "Galpha12 and galpha13 are phosphorylated during platelet activation". The Journal of ... "G proteins of the G12 family are activated via thromboxane A2 and thrombin receptors in human platelets". Proceedings of the ... Offermanns S, Mancino V, Revel JP, Simon MI (Jan 1997). "Vascular system defects and impaired cell chemokinesis as a result of ... "Mutation of an N-terminal acidic-rich region of p115-RhoGEF dissociates alpha13 binding and alpha13-promoted plasma membrane ...

*Prostaglandin

Conversely, thromboxanes (produced by platelet cells) are vasoconstrictors and facilitate platelet aggregation. Their name ... They are produced by almost all nucleated cells. They are autocrine and paracrine lipid mediators that act upon platelets, ... "Activation of the murine EP3 receptor for PGE2 inhibits cAMP production and promotes platelet aggregation". Journal of Clinical ... Cyclooxygenases blocking by lornoxicam in acute stage of inflammation reduced the frequency of membrane formation by 43% in the ...

*Biochemical cascade

After activation of these enzymes, some adaptor proteins are phosphorylated, like BLNK (B cells) and LAT (T cells). These ... platelet-derived thromboxane A2 (TxA2) (TP receptor) and ADP (P2Y1 and P2Y12 receptors) that is either released from damaged ... In somatic cells it binds to receptors in nucleus; however, in spermatozoon its receptors are present in plasmatic membrane. ... The blood cells (erythrocytes, leukocytes and platelets) are produced by hematopoiesis. The erythrocytes have as main function ...

*Coagulation

... platelet factor 4, and thromboxane A2 (TXA2), which, in turn, activate additional platelets. The granules' contents activate a ... cAMP inhibits platelet activation by decreasing cytosolic levels of calcium and, by doing so, inhibits the release of granules ... a platelet membrane constituent) are required for the tenase and prothrombinase complexes to function. Calcium mediates the ... Hoffman, M; Monroe DM, 3rd (June 2001). "A cell-based model of hemostasis" (PDF). Thrombosis and haemostasis. 85 (6): 958-65. ...

*Aspirin

Thromboxanes are responsible for the aggregation of platelets that form blood clots. Heart attacks are caused primarily by ... Acetylsalicylic acid is quickly absorbed through the cell membrane in the acidic conditions of the stomach. The increased pH ... "Effects of low-to-high doses of aspirin on platelet aggregability and metabolites of thromboxane A2 and prostacyclin". Stroke. ... Guitton MJ, Caston J, Ruel J, Johnson RM, Pujol R, Puel JL (2003). "Salicylate induces tinnitus through activation of cochlear ...
In this study, we show that the platelet surface expression of glycoprotein (GP) V is regulated by two independent mechanisms. While confirming that both thrombin and neutrophil elastase proteolyse GPV, we show that neutrophil cathepsin G, thrombin receptor activating peptide (TRAP), and a combination of ADP and epinephrine can each result in a decrease in the platelet surface expression of GPV by a nonproteolytic mechanism: a cytoskeletal-mediated redistribution of platelet surface GPV to the surface-connected canalicular system (SCCS). Four independent lines of evidence documented the nonproteolytic nature of this decrease in the platelet surface expression of GPV. First, flow cytometric studies showed that cathepsin G, TRAP, and ADP/epinephrine decreased the platelet surface expression of GPV without changing the total platelet content of GPV. Second, immunoelectron microscopy directly demonstrated ...
Platelet storage pool deficiency is a type of coagulopathy characterized by defects in the granules in platelets, particularly a lack of granular non-metabolic ADP. Individuals with ADP deficient storage pool disease present a prolonged bleeding time due to impaired aggregation response to fibrillar collagen.[citation needed] The presentation (signs/symptoms) of an individual with platelet storage pool deficiency is as follows: Unusual bleeding(after surgical procedure) Anemia Decrease mean platelet volume Myelodysplasia The condition of platelet storage pool deficiency can be acquired or inherited(genetically passed on from the individuals parents).Some of the causes of platelet storage pool deficiency when acquired are: Hairy-cell leukemia Cardiovascular bypass In terms of the pathophysiology of platelet storage pool deficiency one must consider several ...
The ability of high shear to activate platelets and induce their adhesion and aggregation has been well studied (Ruggeri, 1993; Kroll et al., 1996; Frojmovic, 1998). The importance of shear in platelet adhesion and aggregation has been viewed in the perspective of arterial stenosis caused by atherosclerotic plaques in the coronary, carotid, and peripheral arteries. The interaction of vWF with the glycoprotein Ib/IX/V complex is the initial step that is followed by the binding of vWF to glycoprotein IIb/IIIa to induce platelet activation and aggregation (Kroll et al., 1996). Shear-induced platelet aggregation is often associated with platelet thrombus formation (Kroll et al., 1996). The exposed subendothelium in pathological conditions can serve as the substrate for platelet adhesion and aggregation under elevated shear stress. Such shear-induced ...
Background: Coated-platelets, a subset of activated platelets observed with dual-agonist stimulation with collagen and thrombin, represent 30% of the platelet population in normal controls. In recently published work, we have shown that elevated coated-platelet levels (,45%) are predictive of stroke in asymptomatic carotid stenosis. We now investigate if platelet count and mean platelet volume (MPV) are related to coated-platelet levels.. Methods: Coated-platelet levels were measured in a cohort of asymptomatic outpatients referred for carotid ultrasound studies. Platelet count and mean platelet volume for each subject were recorded from the VA electronic medical record at the closest possible time period (within ≤6 months) to the date of coated-platelet sample. Correlations between each ...
With platelet activation, there is modulation of platelet surface molecule expression. In flow cytometric analyses of in vivo platelet activation, results are often confounded by activation induced in vitro by the preparative procedures. It is particularly important therefore to prevent or retard platelet activation as soon as possible after withdrawal of the blood sample. Taking blood into paraformaldehyde, or fixing the cells with paraformaldehyde as soon as possible after withdrawal, has been employed to prevent platelet activation in vitro, but paraformaldehyde-fixed platelets cannot be further used in functional studies. We investigated the efficacy of Diatube-H, a commercially available combination of platelet antagonists (theophylline, adenosine, and dipyridamole), in ...
Introduction: S100A1 is a member of the S100 family of calcium-binding proteins. S100A1 controls Ca2+ dynamics in cardiomyocytes and plays an important role in heart failure. S100A1 is also strongly expressed in mouse platelets, but its role in platelet biology has not been investigated.. Goal: To determine the role of S100A1 in platelet activation and thrombosis.. Methods and Results: Platelet activation in response to threshold levels of convulxin, a specific agonist for the collagen receptor GPVI, showed significantly increased activation of αIIbβ3 integrin and α-granule release in S100A1-deficient (SKO) platelets compared with wild-type (WT) platelets. Consistently, SKO platelets also showed a more robust aggregation response to convulxin and collagen. In contrast, SKO ...
TY - JOUR. T1 - Influence of rheologic changes and platelet-neutrophil interactions on cell filtration in sepsis. AU - Kirschenbaum, Linda A.. AU - Aziz, Mohammed. AU - Astiz, Mark E.. AU - Saha, Dhanonjoy C.. AU - Rackow, Eric C.. PY - 2000/1/1. Y1 - 2000/1/1. N2 - We examined the role of erythrocyte (red blood cell; RBC) aggregation and deformability, neutrophil (polymorphonuclear neutrophil; PMN) deformability, whole-blood viscosity, and platelet-neutrophil interactions on cell filtration in subjects who were critically ill with sepsis (CIS), critically ill noninfected subjects (CINS), and healthy controls (C). We assessed cell deformability by filtration through filters of 5-μm pore size. Whole blood, RBC, PMN, and combinations of PMN and RBC were studied. Viscometry was done on isolated RBC. Platelet-PMN interactions were assessed with monoclonal antibodies to CD41 and activated CD53 ...
MalaCards based summary : Mean Platelet Volume/count Quantitative Trait Locus 5, is also known as mean platelet volume qtl5. An important gene associated with Mean Platelet Volume/count Quantitative Trait Locus 5 is MPVQTL5 (Mean Platelet Volume QTL5 ...
Oxidized LDL and platelets play a central role in the pathogenesis of atherosclerosis and ischemic cardiovascular diseases. Lysophosphatidic acid (LPA) is a thrombogenic substance that accumulates in mildly-oxidized LDL and in human atherosclerotic lesions, and is responsible for the initial platelet activation, shape change, induced by mildly-oxidized LDL and extracts of lipid-rich atherosclerotic plaques (Siess et al., 1999 Proc Natl Acad Sci USA 1999). LPA directly induced platelet shape change in blood and platelet-rich plasma (PRP) obtained from all blood donors. Albumin was one of the main inhibiting factors of platelet shape change in plasma. Interestingly LPA, at concentrations slightly above plasma levels, induced platelet shape change and aggregation in blood. 1-alkyl-LPA (16:0) was almost 20-fold more potent than 1-acyl-LPA (16:0). LPA-stimulated ...
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Platelet aggregation requires the binding of fibrinogen to its receptor, a heterodimer consisting of the plasma-membrane glycoproteins (GP) IIb and IIIa. Although the GPIIb-IIIa complex is present on the surface of unstimulated platelets, it binds fibrinogen only after platelet activation. We have used an immunogold-surface replica technique to study the distribution of GPIIb-IIIa and bound fibrinogen over broad areas of surface membranes in unstimulated, as well as thrombin-activated and ADP-activated human platelets. We found that the immunogold-labeled GPIIb-IIIa was monodispersed over the surface of unstimulated platelets, although the cell surface lacked immunoreactive fibrinogen. On thrombin-stimulated platelets, approximately 65% of the GPIIb-IIIa molecules were in ...
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Platelet membrane glycoprotein Ib (GPIb), a receptor for von Willebrand factor and thrombin, is present on the platelet surface membrane, in intraplatelet stores, and in plasma (as the proteolytic fragment glycocalicin). We examined the hypothesis that after plasmin-mediated cleavage of platelet surface GPIb, platelets can replenish their surface GPIb pool. Incubation of washed platelets with plasmin (1 hour, 22 degrees C) resulted in loss of platelet surface GPIb, but further incubation (3 hours, 37 degrees C) in autologous plasma resulted in restoration of platelet surface GPIb, as determined by ristocetin-induced platelet agglutination and a flow cytometric assay of platelet binding of three GPIb-specific monoclonal antibodies. Despite the restoration of ...
A method for determining platelet activation by utilizing numeric counts of platelets before a sample of platelets has been activated and after the activatable platelets are activated with a platelet activation agonist and using the difference between such counts as an, indication of the platelet activity of the sample. There is also disclosed a method for using the electronic impedance cell counting technique for determining platelet activation wherein EDTA is used as a preservative by counting the platelets in an EDTA preserved sample using an electronic impedance cell counting technique and subtracting from that number the number of platelets remaining after the activatable ...
inbook{d2d8fceb-9b60-4916-ad95-3b1f6f9113f7, abstract = {,p,Many pathogenic bacteria have been reported to interact with human platelets to mediate platelet activation and aggregation. The importance of these interactions to the immune response or pathogenesis of bacterial infection has not been clarified. It may therefore be valuable to assess platelet responses mediated by diverse strains of bacteria. Here, I describe a method to study platelet integrin activation and granule release using flow cytometry, and a complementary method to study platelet aggregation using a dedicated platelet aggregometer. The combination of these methods represents a rapid and cost-effective strategy to provide mechanistic insight on the type of platelet response mediated by the bacteria.,/p,}, author = {Shannon, Oonagh}, issn = {10643745}, keyword = ...
Platelet-fibrin thrombi in the lumen of atherostenotic carotid arteries may underlie transient ischemic attacks and cerebral infarction. For this reason, we investigated the antiplatelet and antithrombotic effects of a novel and potent platelet fibrinogen receptor (glycoprotein IIb/IIIa) antagonist (SK&F 106760).. The effects of 0.1-3.0 mg/kg i.v. SK&F 106760 on platelet aggregation were examined ex vivo in canine platelet-rich plasma (n = 20). In addition, the antithrombotic effects of SK&F 106760 were compared with those of aspirin in an acute canine model of extracranial carotid artery thrombosis with high-grade stenosis. Sham-operated (n = 4), vehicle-treated (n = 6), SK&F 106760-treated (n = 8), aspirin-treated (n = 9), and SK&F 106760+aspirin-treated (n = 5) dogs were examined.. The intravenous administration of SK&F 106760 caused a dose-related inhibition of ex vivo platelet aggregation. In the ...
SOUZA, AM et al. Platelet indices in dogs with thrombocytopenia and dogs with normal platelet counts. Arch. med. vet. [online]. 2016, vol.48, n.3, pp.277-281. ISSN 0301-732X. http://dx.doi.org/10.4067/S0301-732X2016000300005.. It is well known that thrombocytopenia is the most commonly acquired haemostatic disorder in dogs and can be potentially life-threatening. With the use of automated analysers, platelet indices such as Mean Platelet Volume (MPV), Platelet Distribution Width (PDW), and Platelet Large Cell Ratio (P-LCR), became routinely available, allowing data comparison and error checks which results in a more effective quality control. The aim of this study was to evaluate the pattern of platelet indices (MPV, PDW and P-LCR) in dogs with thrombocytopenia and with normal platelet values. The results of 351 CBCs processed in an automated veterinary ...
Giant platelet disorders are rare disorders featuring abnormally large platelets, thrombocytopenia and a tendency to bleeding. Giant platelets cannot stick adequately to an injured blood vessel walls, resulting in abnormal bleeding when injured. Giant platelet disorder occurs for inherited diseases like Bernard-Soulier syndrome, gray platelet syndrome and May-Hegglin anomaly. Symptoms usually present from the period of birth to early childhood as: nose bleeds, bruising, and/or gum bleeding. Problems later in life may arise from anything that can cause internal bleeding such as: stomach ulcers, surgery, trauma, or menstruation. Abnormality of the abdomen, nosebleeds, heavy menstrual bleeding, purpura, too few platelets circulating in the blood, and prolonged bleeding time have also been listed as symptoms of various Giant Platelet Disorders. ...
human platelet receptor for type III collagen: MW 68-72 kDa; platelet receptor involved in platelet interaction with type III collagen, localized within platelet lipid rafts where it could interact with other platelet receptors for collagen (GP VI and alpha2beta1 integrin) for efficient platelet activation
Using a highly sensitive marker of platelet function, we have shown that platelet activation is increased in patients with stable COPD compared with controls matched for age and previous cigarette smoke exposure. Moreover, platelet activation is further increased in patients with COPD during an acute exacerbation. Taken together, these findings suggest that platelet function may be modified as a consequence of COPD.. We suggest that platelet activation represents a novel mechanism linking COPD, inflammation and cardiovascular disease. Platelet activation is known to predict an adverse outcome in patients with stable coronary disease15 and to identify patients likely to have recurrent cardiovascular events following percutaneous coronary intervention.16 The interaction between platelets and inflammatory ...
TY - JOUR. T1 - A study of whole blood platelet and white cell aggregation using a laser flow aggregometer. AU - Sun, J.. AU - Abel, E. W.. AU - Bancroft, A.. AU - McLaren, M.. AU - Belch, J. J. F.. PY - 2003. Y1 - 2003. N2 - Both platelet aggregation and white blood cell aggregation are involved in pathological processes such as thrombosis, atherosclerosis and chronic inflammation. People in older age groups are likely to suffer from cardiovascular diseases and may have increased white cell and platelet aggregation which could contribute to this increased risk. This study aimed to compare white cell and platelet aggregation between different age and gender groups. Whole blood white cell aggregation and platelet aggregation were carried out on healthy volunteers using cytometric techniques. It was found that both white cell ...
Systematic review (Open Access) on the comparison of different platelet transfusion thresholds prior to insertion of central lines in patients with thrombocytopenia from Cochrane Database of Systematic Reviews Comparison of different platelet transfusion thresholds prior to insertion of central lines in patients with thrombocytopenia #vascularaccess #FOAMva #FOAMed #FOAMcc #POCUS #patientsafety
Megakaryocytes generate platelets by remodeling their cytoplasm into long proplatelet extensions, which serve as assembly lines for platelet production. Although the mechanics of proplatelet elongation have been studied, the terminal steps of proplatelet maturation and platelet release remain poorly understood. To elucidate this process, released proplatelets were isolated, and their conversion into individual platelets was assessed. This enabled us to (a) define and quantify the different stages in platelet maturation, (b) identify a new intermediate stage in platelet production, the preplatelet, (c) delineate the cytoskeletal mechanics involved in preplatelet/proplatelet interconversion, and (d) model proplatelet fission ...
Platelet Aggregation Test - The DiaMed Impact R tests platelet function Specializing in Platelet Function testing, bleeding time, platelet count, platelet function analysis. Bleeding time lab test and platelet function analyzer ideal tool for platelet function studies.
Approach and Results-To model standard antiplatelet therapy, platelets were treated in vitro with aspirin, the P2Y12 receptor blocker prasugrel active metabolite, and aspirin plus prasugrel active metabolite. Different proportions of uninhibited platelets were then introduced. Light transmission aggregometry analysis demonstrated clear positive associations between proportions of drug-free platelets and percentage platelet aggregation in response to a range of platelet agonists. Using differential platelet labeling coupled with advanced flow cytometry and confocal imaging, we found aggregates formed in mixtures of aspirin-inhibited platelets and drug-free platelets were characterized by intermingled platelet populations. This distribution is in accordance ...
Cardiovascular disease is a chronic disease influenced by many factors, with activated blood platelets being one of them. Platelets play a central role in the formation of plaques within blood vessels, contributing to early inflammatory events. Consumption of diets rich in plant-based products protects against the development of cardiovascular disease. Polyphenols, which are secondary plant metabolites found in a wide range of foodstuffs and beverages, may be partially responsible for these effects. Their protective properties include inhibitory effects on platelet function in vitro and in vivo. However, the bioavailability of many polyphenols is poor and it is unclear whether sufficient quantities can be obtained by dietary means to exert protective effects. Consequently, this review summarizes 25 well-controlled human intervention studies examining the effect of polyphenol-rich diets on platelet function. ...
Our finding that mean platelet component is lower in acute myocardial infarction than in unstable angina, reflecting greater platelet activation, confirms the central role of thrombogenicity in the pathogenesis of acute coronary syndromes. Indeed, platelet activation was an independent predictor of the mode of presentation and, even in the subgroup of patients with unstable angina at high risk of future events, platelet activation was significantly lower than in those with myocardial infarction.. Some studies have not found a difference in platelet activation between unstable angina and myocardial infarction. However, Garlichs and colleagues2 found greater expression of the CD40 ligand in unstable angina than in myocardial infarction. This appears counterintuitive but may reflect greater hydrolysis and release of the ligand in myocardial infarction. Mathur ...
BioAssay record AID 488052 submitted by ChEMBL: Antiplatelet activity in human platelet rich plasma assessed as inhibition of ADP-induced platelet aggregation measured for 6 mins by aggregometry.
The use of arachidonic acid (AA) to stimulate platelets is considered as a specific approach to study aspirin treatment efficacy. However, very high concentrations of AA are used, and it has been previously reported that AA can induce cell lysis in other settings. Several clinical studies have reported decreased responses to AA in whole blood tests in the presence of clopidogrel. Our aim was to investigate whether unspecific effects contribute to AA-induced aggregation and platelet activation in light transmission aggregometry (LTA) in platelet-rich plasma (PRP), and in assays using whole blood, multiple electrode aggregometry (MEA, Multiplate?), and flow cytometry. We report that cell lysis, especially of red blood cells, does occur at concentrations of AA used in the clinical tests and that ADP is very important for the AA-induced platelet ...
Platelets labeled with indium-111 have been used successfully as a marker of active thrombosis in man. To establish the diagnostic accuracy of platelet scintigraphy in comparison to contrast venography in the diagnosis of acute lower limb venous thrombosis, we evaluated 103 consecutive patients divided into two groups. Platelets were labeled by the indium-111 oxine method. Patients from group I (n = 73, 56 had venograms) were asymptomatic and underwent platelet scintigraphy 1.1 +/- 0.6 days (mean +/- 1 SD) after a major orthopedic procedure. Patients from group II (n = 30, all had venograms) were symptomatic and underwent platelet scintigraphy 1.2 +/- 1.7 days after venography. In group II, 15 patients with positive findings on contrast venography were treated with intravenous heparin; five others with positive venograms did not receive heparin until platelet scintigraphy ...
TY - JOUR. T1 - Inhibitory signaling of 17β-estradiol in platelet activation. T2 - The pivotal role of cyclic AMP-mediated nitric oxide synthase activation. AU - Wu, Gong-Jhe. AU - Lee, Jie Jen. AU - Chou, Duen-Suey. AU - Jayakumar, Thanasekaran. AU - Hsiao, George. AU - Chen, Wei Fan. AU - Sheu, Joen-Rong. PY - 2010/12/15. Y1 - 2010/12/15. N2 - Arterial thromboses are mostly composed of platelets adherent to ruptured endothelial surfaces. Platelets are anucleated cells; therefore, they represent an excellent and unique model to selectively investigate the signaling pathways mediating the nongenomic effects of estrogen. The aim of this study was to examine the signal transduction pathways of 17β-estradiol in preventing platelet activation. In this study, 17β-estradiol (5~10μM) exhibited more-potent activity of inhibiting ...
Reuters) - Scientists have for the first time created blood platelet cells by reprogramming stem cells derived from adult cells, offering the potential for a renewable supply of the fragile blood component.. Researchers at the Center for iPS Cell Research and Application at Kyoto University in Japan presented data here at a meeting of the American Society of Hematology showing they were able to create the cells in the laboratory and confirm they had the same life span as normal human platelets when infused in mice.. "The next step will be to conduct a trial to determine whether our platelets can function in the human body and potentially provide a stable supply of platelets at a predefined quality and quantity that can then be used for transfusion therapy," D. Koji Eto, professor at the Kyoto center and ...
Normal primary platelet aggregation requires agonist-mediated activation of membrane GPIIb-IIIa, binding of fibrinogen to GPIIb-IIIa, and cellular events after ligand binding. PAC1 monoclonal antibody distinguishes between resting and activated states of GPIIb-IIIa, and other antibodies preferentially recognize GPIIb (PMI-1) or IIIa (anti-LIBS1) after the binding of fibrinogen or fibrinogen-mimetic peptides, such as GRGDSP. Using these antibodies and platelet flow cytometry, we studied two distinct persistent platelet aggregation abnormalities. Platelets from a thrombasthenic variant, which contained near-normal amounts of GPIIb-IIIa, failed to aggregate or bind PAC1 in response to agonists. In addition, GRGDSP, which binds to normal GPIIb-IIIa without prior cell activation, failed to increase the binding of PMI-1 or anti-LIBS1 to the ...
Platelets are cell fragments which are mainly an essential component when it comes to blood clotting and coagulation. The platelets along with the red blood cells and white blood cells, function together for the regulation and normal functioning of blood in our body. The blood cells have each of their own different life span as well as different functions. Among these three, the platelets are the smallest but one of the most important factors in blood clotting. If the platelets dont get regulated properly, such as when they dont get renewed at normal intervals, then the blood dysfunction or disorder might occur.. The general lifespan of a platelet is about 10 days. The normal platelet count in the human blood ranges from 150,000 to 450,000 per micro liter of blood. The ...
SUMMARY Acquired qualitative platelet disorders are frequent causes of abnormal platelet function measured in vitro, although by themselves are usually associated with little or no clinical bleeding. However, there are important exceptions. Nevertheless, their major clinical impact becomes apparent in the additional presence of thrombocytopenia, or additional acquired or congenital disorders of hemostasis. Acquired disorders of platelet function can be conveniently classified into those that result from drugs, hematologic diseases, and systemic disorders. Drugs are the most frequent cause of acquired qualitative platelet dysfunction. Aspirin is the most notable drug in this regard because of its frequent use, its irreversible effect on platelet prostaglandin synthesis, and its documented effect on hemostatic competency, although this effect is minimal in normal individuals. Other nonsteroidal antiinflammatory drugs ...
This study is the first to show that platelet activation is increased by the brachytherapy currently applied in clinical practice. A notable increase was found after brachytherapy compared with PCI without irradiation. We have previously identified increased platelet activation after conventional PCI as an independent risk factor for acute ischaemic events.20 The data on radiation delivery devices submitted for US Food and Drug Administration (FDA) approval showed that patients treated with radiation benefit from a reduction in recurrent stenosis but also have the disadvantage of an increased rate of thrombotic events.192324 Thrombotic occlusions are associated with increased mortality after PCI21 and an increased risk of myocardial infarctions after VBT.1419232526 The increase in platelet activation after brachytherapy is not suppressed by concomitant treatment with aspirin and clopidogrel. Both drugs were ...
Results: 22 hypoxemic patients were selected for the study based on their diagnosis of COPD (from history and spirometry) along with age and sex matched controls. Presence of comorbidities and other factors that cause platelet activation were excluded. Level of platelet aggregation was determined by several experiments. By an aggregometer using platelet agonists (thrombin and ADP) it was found that platelet aggregation was significantly higher in hypoxemic COPD patients than normal healthy controls. Fluorescence spectrophotometer was used to measure intracellular calcium as a marker of platelet activation and it was found that hypoxemic COPD patients had significantly higher platelet aggregation than normal healthy controls. However no significant difference was found in other markers of platelet activation studied namely ...
Extracts of Helicobacter pylori (HP) have been shown to induce leukocyte adhesion in mesenteric venules, but the effects of HP infection on gastric microvessels are unknown. Inflammatory cell interactions in the gastric microcirculation were studied by intravital videomicroscopy in mice inoculated with either saline or fresh isolates of HP. Platelet aggregates were detected and quantified in murine portal blood, while endothelial P-selectin expression was determined using the dual radiolabeled mAb technique. Platelet activation and aggregation were studied in HP-infected patients and controls by measuring the platelet-aggregate ratio and platelet P-selectin expression. HP infection induced a marked increase in the flux of rolling leukocytes and the appearance of platelet and leukocyte- platelet aggregates in murine gastric venules. The HP-induced rolling and ...
This thesis describes the Chandler loop, which makes it possible to conduct studies in vitro of molecular and cellular interactions between whole blood and stents. It was possible to monitor activation and inhibition of the cascades systems, leukocytes and platelets by combining different platelet inhibitors and heparin coating of stents. The clinical study was performed on patients with ACS undergoing PCI and stent implantation. In this study platelet activation markers P-selectin, and αIIb/β3 as well as inflammatory markers were followed from baseline during the first 48 hours post-PCI. The same parameters were evaluated in healthy controls for comparison at baseline. In vitro: The activation of blood in the Chandler loops were more pronounced for unmodified stent grafts than for partially heparin coated stent grafts. Heparin coated stent grafts dreated the same ...
In a previous report, we suggested that platelet hyperactivity, possibly through stimulated free radical-induced arachidonate acid metabolism, might be involved in the known thrombogenic risk of OC intake.15 We were also the first to show that dietary FD potentiated platelet activation.7 The present study was designed to determine whether FD could amplify OC effects and whether an impaired folate metabolism could contribute to the thrombogenicity of OC. We found that feeding rats with a folic acid-deficient diet enhanced OC-induced platelet hyperactivity. Although a rat model has been used with a high dose of estrogen that may not be comparable with that for women, we also observed that OC treatment led to a loss of folates associated with moderate hyperhomocysteinemia. We further suggested that involvement of an impaired folate metabolism in the prothrombotic effects caused by OC might be secondary to the OC-induced oxidative stress, which ...
Protease-activated receptors (PAR)-1 and -4 are the principal receptors for thrombin-mediated platelet activation. Functional genetic variation has been described in the human PAR1 gene, but not in the PAR4 gene (F2RL3). We sought to identify variants in and around F2RL3 and to determine their association with perioperative myocardial injury (PMI) after coronary artery bypass graft surgery. We further explored possible mechanisms for F2RL3 single nucleotide polymorphism (SNP) associations with PMI including altered receptor expression and platelet activation. Twenty-three SNPs in the F2RL3 gene region were genotyped in two phases in 934 Caucasian subjects. Platelets from 43 subjects (23 major allele, 20 risk allele) homozygous for rs773857 (SNP with the strongest association with PMI) underwent flow cytometry to assess PAR4 receptor number and response to activation by a specific PAR4 ...
We investigated the effects of dietary polyunsaturated fatty acids (PUFAs) on blood lipids and processes that determine hemostatic potential: platelet activation, coagulation, and fibrinolysis. For 8 to 10 weeks, Wistar rats were fed a high-fat diet containing various amounts (2% to 16%) of n-3 PUFAs derived from fish oil (FO) or a diet enriched in n-6 PUFAs from sunflower seed oil (SO). Only the FO diets caused a reduction in mean platelet volume, platelet arachidonate level, and formation of thromboxane B2 by activated platelets, but neither of the diets had a measurable effect on platelet activation. The FO-rich diets decreased the plasma concentrations of triglycerides and cholesterol, whereas the SO diet reduced triglycerides only. Parameters of fibrinolysis and standard coagulation times, ie, activated partial thromboplastin time and prothrombin time, ...
Postprandial hyperglycemia is associated with platelet activation. We thus investigated if meal-induced platelet activation could be attenuated by meal insulin. A randomized, double-blind, cross-over study was performed to compare postprandial platelet activation after premeal injections of placebo or insulin aspart (0.1 and 0.2 units/kg) in 18 patients with type 2 diabetes mellitus (T2DM). Platelet activation was assessed by flow cytometry, without and with stimulation by the thromboxane analog U46619 or ADP. Measurements were before and after premeal blood glucose standardization (to 6-7 mmol/L by insulin infusion, if needed) and at 90 min after the meal. Premeal insulin reduced postprandial hyperglycemia by 2-3 mmol/L compared with placebo. Postmeal insulin levels were doubled with placebo and further elevated with insulin injections. The standardized ...
Second hand cigarette smoke (SHS) is one of the major risk factors for cardiovascular disease (CVD) and has been shown to substantiate platelet activation and aggregation in several studies [1, 2]. Most of these studies, under chronic or acute exposure conditions or over prolonged exposure, do not represent the initiation of a disease state or hematological damage under normal levels of cigarette smoke. These above studies of platelet activation with SHS together with our previous in-vitro studies demonstrating cardio-protective effects of nicotine [3], have motivated the present investigation of physiological levels of SHS exposure on human subjects and within an in-vitro endothelial cell-platelet system, with cigarettes (or smoke extracts) of varying nicotine content to confirm analogous cardio-protective effects of nicotine.. Copyright © 2007 by ASME ...
Platelets play a central role in maintaining biological hemostasis. Inappropriate platelet activation is responsible for thrombotic diseases such as myocardial infarction and stroke. Therefore, novel agents that can inhibit platelet activation are necessary. However, assays that monitor platelet aggregation are generally time-consuming and require high volumes of blood and specialized equipment. Therefore, a medium- to high-throughput assay that can monitor platelet aggregation would be considered useful. Such an assay should be sensitive, comparable to the "gold standard" assay of platelet aggregometry, and able to monitor multiple samples simultaneously but with low assay volumes. We have developed such a microtiter assay. It can assay an average of 60 independent treatments per 60 ml blood donation and demonstrates greater sensitivity than the current ...
Platelets play a central role in maintaining biological hemostasis. Inappropriate platelet activation is responsible for thrombotic diseases such as myocardial infarction and stroke. Therefore, novel agents that can inhibit platelet activation are necessary. However, assays that monitor platelet aggregation are generally time-consuming and require high volumes of blood and specialized equipment. Therefore, a medium- to high-throughput assay that can monitor platelet aggregation would be considered useful. Such an assay should be sensitive, comparable to the "gold standard" assay of platelet aggregometry, and able to monitor multiple samples simultaneously but with low assay volumes. We have developed such a microtiter assay. It can assay an average of 60 independent treatments per 60 ml blood donation and demonstrates greater sensitivity than the current ...
I have trouble collecting blood from mice for measuring platelet activation. The treatment with a drug is supposed to make platelets more active, but the non-treated controls show large deviation in platelet activation so no measurements are possible. Speaking with local experts helped a bit, but apparently they have the same problem. Apparently it is all about collecting the blood in a special way. Any ideas ...
We propose that TG and TEG will be more sensitive than traditional coagulation assays to detect physiologic variation in hemostasis, fibrinolysis, and platelet activation throughout the menstrual cycle. We expect that TG and TEG will better discriminate patients with vWD than traditional coagulation studies during the menstrual cycle. In this study we plan to measure TG and TEG in healthy women and women with von Willebrands disorder during four phases of the menstrual cycle. We will compare specific measurements of endogenous thrombin generation potential from the TG and fibrinolysis and platelet activation from the TEG with standard measures of coagulation, fibrinolysis, and platelet activation markers during the menstrual cycle ...
Beta-thromboglobulin (β-thromboglobulin, also called Pro-Platelet basic protein) is a protein that is stored in alpha-granules of platelets and released in large amounts after platelet activation. It is a type of Chemokine (C-X-C motif) ligand 7. It is a chemoattractant, strongly for fibroblasts and weakly for neutrophils. It is a stimulator of mitogenesis, extracellular matrix synthesis, glucose metabolism, and plasminogen activator synthesis in human fibroblasts. Beta-Thromboglobulin also affects megakaryocyte maturation, and thus helps in regulating platelet production. Levels of Beta-Thromboglobulin is used to index platelet activation. It is measured by ELISA in blood plasma or urine, and often in conjunction with Platelet factor 4) It is elevated in diabetes mellitus. Cytokines & Cells Online Pathfinder Encyclopaedia ...
Enhanced thromboxane biosynthesis has previously been reported in patients with acute ischemic stroke. In this study we examined the time course of thromboxane biosynthesis after the onset of symptoms in 13 patients with acute cerebral infarction.. We obtained five to eight consecutive 6-hour urine samples from each of these 13 patients within the first 48 hours after onset of symptoms to study the dynamics of platelet activation in this setting. The urinary excretion of the major enzymatic metabolite of thromboxane B2, 11-dehydro-thromboxane B2, was measured by a previously validated radioimmunoassay. The excretion rate was compared with that of 20 control patients with nonvascular neurological diseases.. Eleven patients (85%) had at least one value exceeding 2 SD of the control mean (251 pmol/mmol creatinine). The proportion of samples with an elevated 11-dehydro-thromboxane B2 level was ...
Thrombin signaling of platelets is mediated by a G protein-coupled protease-activated receptor (PAR). The PAR is activated after thrombin binding and subsequent cleavage of the amino terminal end of the receptor. This new amino terminus acts as a tethered ligand and binds intramolecularly to the body of the PAR, resulting in a transmembrane signal. Synthetic thrombin receptor agonist peptides (TRAP) of 6 residues (SFLLRN) and 14 residues (SFLLRNPNDKYEPF), respectively corresponding to aa42-47 and aa42-55 of the human thrombin receptor were found to be as effective as thrombin for Ca2+ mobilization. It was also shown that these peptides are far less active on pig and guinea pig platelets, whereas completely inactive on rat and rabbit platelets.. ...
Platelets play a key and beneficial role for primary hemostasis on the disruption of the integrity of vessel wall. Platelet adhesion and activation at sites of vascular wall injury is initiated by adhesion to adhesive macromolecules, such as collagen and von Willebrand factor (vWF), or by soluble platelet agonists, such as ADP, thrombin, and thromboxane A2. Different receptors are stimulated by various agonists, almost converging in increasing intracellular Ca2+ concentration that stimulate platelet shape change and granule secretion and ultimately induce the "inside-out" signaling process leading to activation of the ligand-binding function of integrin alpha IIb beta 3. Binding of alpha IIb beta 3 to its ligands, mainly fibrinogen, mediates platelet adhesion and aggregation and triggers "outside-in" signaling, resulting in ...
Background-Selective inhibitors of cyclooxygenase-2 (COX-2) increase the risk of myocardial infarction and thrombotic events, but the responsible mechanisms are not fully understood. Methods and Results-We found that ferric chloride-induced arterial thrombus formation was significantly greater in COX-2 knockout (KO) compared to wild type (WT) mice. Cross-transfusion experiments excluded the likelihood that COX-2KO platelets, despite enhanced aggregation responses to collagen and thrombin, are responsible for increased arterial thrombus formation in COX-2KO mice. Importantly, we observed that COX-2 deletion decreased prostacyclin (PGI2) synthase and production, proliferator-activated receptor (PPAR)δ and sirtuin-1 (SIRT1) expression, with consequent increased upregulation of tissue factor (TF), the primary initiator of blood coagulation. Treatment of WT mice with a PGI2 receptor (IP) antagonist or a PPARδ antagonist, which predisposes to arterial thombosis, decreased SIRT1 ...
OBJECTIVES: We sought to examine whether patients with stable coronary artery disease (CAD) have increased platelet reactivity and an enhanced propensity to form monocyte-platelet aggregates. BACKGROUND: Platelet-dependent thrombosis and leukocyte infiltration into the vessel wall are characteristic cellular events seen in atherosclerosis. METHODS: Anticoagulated peripheral venous blood from 19 patients with stable CAD and 19 normal control subjects was incubated with or without various platelet agonists and analyzed by whole blood flow cytometry. RESULTS: Circulating degranulated platelets were increased in patients with CAD compared with control subjects (mean [+/- SEM] percent P-selectin-positive platelets: 2.1 +/- 0.2 vs. 1.5 +/- 0.2, p andlt; 0.01) and were more reactive to stimulation with 1 micromol/liter of adenosine diphosphate (ADP) (28.7 +/- 3.9 ...
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Full Text - The cardiovascular effects of testosterone and dihydrotestosterone are generally attributed to their modulatory action on lipid and glucose metabolism. However, no ex vivo studies suggest that circulating androgen levels influence the activation and reactivity of blood platelets - one of the main components of the haemostasis system directly involved in atherosclerosis. The levels of testosterone, dihydrotestosterone and oestradiol in plasma from men and women aged from 60 to 65 years were measured by LC-MS; the aim was to identify any potential relationships between sex steroid levels and the markers of platelet activation (surface membrane expression of GPII/IIIa complex and P-selectin) and platelet reactivity in response to arachidonate, collagen or ADP, monitored with whole blood aggregometry and flow cytometry. The results of the ex vivo part of the study ...
The TEMPLATE study design will enable unbiased comparison of the effects of TIC versus TIC + ASP on platelet activity in patients with coronary artery disease. It will also enable a longitudinal comparison of the effects TIC and TIC + ASP with the effects of ASP alone in the same patients. The laboratory tests selected for this study will enable measurement of functional platelet responses to a panel of activating agonists using LTA, flow cytometry and flow chamber tests, selected to measure the extent of inhibition of the multiple platelet activation pathways. We will also measure the extent of baseline platelet activity by testing unstimulated platelets by flow cytometry and with the soluble platelet activation biomarker tests. Together, these data will provide a comprehensive description of the overall pharmacodynamic effects of the different ...
Platelets from untreated periodontitis patients are hyper-reactive and form more platelet-leukocyte complexes compared to cells from individuals without periodontitis. It is not known whether the improvement of the periodontal condition achievable by therapy has beneficial effects on the platelet function. We aimed to assess the effects of periodontal therapy on platelet reactivity. Patients with periodontitis (n = 25) but unaffected by any other medical condition or medication were included and donated blood before and after periodontal therapy. Reactivity to ADP or oral bacteria was assessed by flow cytometric analysis of membrane markers (binding of PAC-1, P-selectin, CD63) and platelet-leukocyte complex formation. Reactivity values were expressed as ratio between the stimulated and unstimulated sample. Plasma levels of soluble (s) P-selectin were determined by ...
The work herein examines in vitro platelet aggregation in response to fluid shearing motion. Our specific aim is to characterize shear-induced aggregation by means of kinetic measurements. In doing so we consider plausible physicochemical mechanisms for platelet activation in the shear field. Besides resolving some questions concerning the activation of platelets by shear forces, this study further implicates fluid mechanical factors in thrombosis and arterial disease. Specific results may also apply to the design and evaluation of blood-contacting artificial devices. The experimental procedure centers on the use of a rotational viscometer to apply a controlled shearing motion to platelet suspensions for prescribed times. We quantify aggregation through changes in particle size histograms and associated measures (e.g. total number of particles). Additional insight into the aggregation ...
PAR1, PAR4 and GPIB form functional interdependent units in a receptor complex mediating platelet activation by thrombin in JOURNAL OF THROMBOSIS AND HAEMOSTASIS, vol 9, issue SI, pp 11-11 ...
Phosphatidylinositol 3-kinaseβ (PI3Kβ) plays a predominant role in integrin outside-in signaling and in platelet activation by GPVI engagement. We have shown that the tyrosine kinase Pyk2 mediates PI3Kβ activation downstream of integrin αIIbβ3, and promotes the phosphorylation of the PI3K-associated adaptor protein c-Cbl. In this study, we compared the functional correlation between Pyk2 and PI3Kβ upon recruitment of the two main platelet collagen receptors, integrin α2β1 and GPVI. PI3Kβ-mediated phosphorylation of Akt was inhibited in Pyk2-deficient platelets adherent to monomeric collagen through integrin α2β1, but occurred normally upon GPVI ligation. Integrin α2β1 engagement led to Pyk2-independent association of c-Cbl with PI3K. However, c-Cbl was not phosphorylated in adherent platelets, and phosphorylation of Akt occurred normally in c-Cbl-deficient ...
Tortuous blood vessels are often seen in humans in association with thrombosis, atherosclerosis, hypertension, and aging. Vessel tortuosity can cause high fluid shear stress, likely promoting thrombosis. However, the underlying physical mechanisms and microscale processes are poorly understood. Accordingly, the objectives of this study were to develop and use a new computational approach to determine the effects of venule tortuosity and fluid velocity on thrombus initiation. The transport, collision, shear-induced activation, and receptor-ligand adhesion of individual platelets in thrombus formation were simulated using discrete element method. The shear-induced activation model assumed that a platelet became activated if it experienced a shear stress above a relative critical shear stress or if it contacted an activated platelet. Venules of various levels of tortuosity were simulated for a mean flow ...
Dronedarone has been associated with a reduced number of first hospitalisation due to acute coronary syndromes. Whether this is only due to the reduction in ventricular heart rate and blood pressure or whether other effects of dronedarone may be involved is currently elusive. This study was designed to investigate the role of dronedarone in arterial thrombus formation. C57Bl/6 mice were treated with dronedarone and arterial thrombosis was investigated using a mouse photochemical injury model. Dronedarone inhibited carotid artery thrombus formation in vivo (P , 0.05). Thrombin- and collagen-induced platelet aggregation was impaired in dronedarone-treated mice (P , 0.05), and expression of plasminogen activator inhibitor-1 (PAI1), an inhibitor of the fibrinolytic system, was reduced in the arterial wall (P , 0.05). In contrast, the level of tissue factor (TF), the main trigger of the coagulation cascade, and that of its physiological inhibitor, TF pathway inhibitor, did not differ. Similarly, ...
ible dose of sildenafil during 1 month. In patients with Since endothelial dysfunction is associated with vas- CHF, sildenafil significantly reduced blood pressure, cular inflammation, platelet activation, and rapid pro- resting heart rate and attenuated the heart rate incre- gression of atherosclerosis and its adverse events, strate- ment (6-min treadmill-walking test and maximal exer- gies that enhance NO bioavailability may have a positive cise test, Figure 3) which was attributed to the modula- impact on outcomes in patients with coronary artery dis- tion of the effects of the NO-cGMP pathway on the ease (CAD). Therefore, Halcox et al. [40] hypothesized pacemaker activity of sinoatrial node cells [43]. More- that PDE 5 inhibition with sildenafil may abrogate coro- nary and peripheral vascular endothelial dysfunction in cise and increased the maximal exercise capacity. Treat- patients with CAD, inhibit platelet ...
Erythromelalgia is the main, pathognomonic and presenting symptom in patients with Essential Thrombocythemia and thrombocythemia associated with Polycythemia Vera. Complete relief of erythromelalgic and acrocyanotic pain is obtained with the cyclooxygenase inhibitors aspirin and indomethacin, but not with sodiumsalicylate, dipyridamol, sulfinpyrozone and ticlopedine indicating that platelet-mediated cyclooxygenase metabolites are necessary for erythromelalgia to develop. Local platelet consumption in erythromelalgic areas became evident by the demonstration of arteriolar fibromuscular intimal proliferation and occlusions by platelet-rich thrombi in skin biopsies, by the findings of shortened platelet survival times, significant higher levels of platelet activation markers -thromboglobulin ( -TG), thrombomoduline and increased urinary thromboxane B2 excretion in thrombocythemia patients ...
This is the largest study to date to examine MPV with diabetes and correlate MPV to the degree of glycemic control in a large unselected population. Several small studies have noted a higher MPV in patients with diabetes (21-26). However, the data correlating MPV to glycemic control are conflicting and from relatively small or single-center populations (21-26). Although one study correlated MPV to the presence of metabolic syndrome (27), no study has evaluated MPV and the individual components of the metabolic syndrome. The current analysis is the largest study of platelet activity in diabetes and the only study to evaluate the complex relationship between MPV and diabetes, glycemic control, and the metabolic syndrome with its individual components.. In the current study, platelet activity, as measured by MPV, is significantly higher in the diabetic population and, in particular, in those subjects with diabetes and poor glycemic control. This is consistent with an ...
TY - JOUR. T1 - An ex-vivo model of shear-rate-based activation of blood coagulation. AU - Ranucci, Marco. AU - Ranucci, Matteo. AU - Baryshnikova, Ekaterina. PY - 2018/3/1. Y1 - 2018/3/1. N2 - The study presents a model of shear-stress-based platelet activation. Twenty-eight patients (22 free from anticoagulants and major antiplatelet agents, and six under the effects of P2Y12 platelet inhibitors) participated. The main purpose was to verify the hypothesis that a model of shear-dependent blood activation does not require artificial activators to trigger clot formation. Whole blood collected from the patients received platelet function tests [ADPtest and thrombin receptor-Activating peptide (TRAP)test] and was tested with a cone-on-plate viscosimeter at a shear rate of 100 sS-1. Changes in blood viscosity were characterized by a time-To-gel point (TGP), a maximum clot viscosity and a steady ...
In this study, we investigated the mechanism of platelet activation in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), as well as the activation of the alternative complement pathway by platelets in AAV. CD62P and platelet-leukocyte aggregates in AAV patients were tested by flow cytometry. Platelets were stimulated by plasma from active AAV patients. The effect of the thrombin-protease-activated receptors (PARs) pathway was evaluated by blocking thrombin or PAR1 antagonists. After platelets were activated by plasma from AAV patients, Ca/Mg-Tyrodes buffer and Mg-EGTA buffer were used to measure complement activation in liquid phase and on the surface of platelets. The levels of CD62P-expressing platelets and ...
Platelets play a fundamental role in hemostasis and thrombosis. They are also involved in pathologic conditions resulting from blocked blood vessels, including myocardial infarction and ischemic stroke. Platelet adhesion, activation, and aggregation at sites of vascular injury are regulated by a diverse repertoire of tyrosine kinase-linked and G protein-coupled receptors. Src family kinases (SFKs) play a central role in initiating and propagating signaling from several platelet surface receptors; however, the underlying mechanism of how SFK activity is regulated in platelets remains unclear. CD148 is the only receptor-like protein tyrosine phosphatase identified in platelets to date. In the present study, we show that mutant mice lacking CD148 exhibited a bleeding tendency and defective arterial thrombosis. Basal SFK activity was found to be markedly reduced ...
Summary. Background: Platelet adhesion, activation and aggregation at sites of vascular injury are essential processes for primary hemostasis. Elevation of the intracellular Ca2+ concentration is a central event in platelet activation but the underlying mechanisms are not fully understood. Store-operated calcium entry (SOCE) through Orai1 was shown to be the main Ca2+ influx pathway in murine platelets, but there are additional non-store-operated Ca2+ (non-SOC) and receptor operated Ca2+ (ROC) channels expressed in the platelet plasma membrane.Objective: Canonical transient receptor potential (TRPC) channel 6 is found both in human and murine platelets and has been proposed to mediate diacylglycerol (DAG) activated ROCE but also a role in the regulation of SOCE has been suggested.Methods: To investigate the function of TRPC6 ...
Differences in expression of the platelet activation marker P-selectin (CD62P) between Fabry disease patients and healthy subjects at baseline and after agonist ...
In this blinded, prospective study, we demonstrated aspirin resistance as documented by optical platelet aggregation testing to be negatively associated with long-term outcomes in a population of stable cardiovascular patients. Previous studies have demonstrated aspirin resistance by both clinical evidence of unresponsiveness to aspirin (8)and ex vivo platelet function testing (5,9-13). To date only three studies have evaluated the clinical consequence of aspirin resistance in select populations (14-16). Grotemeyer et al. (14)evaluated 180 acute stroke patients for evidence of aspirins effect on platelet reactivity. Patients with elevated platelet reactivity despite aspirin were more likely to experience vascular death, MI, or CVA. Mueller et al. (15)reported an association between failed inhibition of platelet reactivity by aspirin and risk of reocclusion after peripheral vascular angioplasty in patients with claudication. ...
Platelet activation and aggregation play an important role in the pathogenesis of arterial thrombosis and lead to acute coronary syndrome and complications during and after percutaneous coronary intervention. Clopidogrel, a thienopyridine, inhibits platelet activation induced by adenosine diphosphate (ADP). Alone or in association with aspirin, clopidogrel has successfully proved its benefit in the treatment of atherothrombotic disease (1,2). It also decreases the incidence of coronary artery stent thrombosis (2).. Clopidogrel is a prodrug, and must be metabolized in the liver to acquire its antiaggregation properties. Clopidogrel requires several biotransformation steps, mediated mainly by cytochrome P-450 isoenzymes, to generate an active metabolite. It exerts its antiplatelet effect by forming an inactivating disulfide bond with the platelet P2Y12 ADP receptor. Clopidogrel inhibits the effect of ADP on ...
Inappropriate platelet activation contributes to vascular diseases including stroke and myocardial ischemia. Our laboratory is focused on phospholipid signaling in platelets and its contribution to inappropriate platelet activation. Ongoing projects are directed at understanding the roles of pleckstrin and lipid kinases in platelets. Pleckstrin (p47) was once solely known as an early marker of platelet activation; more recently it has been noted to contain the prototypic Pleckstrin Homology motif. Over the past half dozen years, work derived from our laboratory has demonstrated that pleckstrin plays a dominant role in the reorganization of the platelet, and lymphocyte, cytoskeleton. Furthermore, our laboratory has established these effects are regulated by pleckstrin phosphorylation, require critical lipid-binding residues ...
Dual antiplatelet therapy coupling aspirin with a P2Y12 inhibitor is currently the therapy of choice for the prevention of recurrent thrombotic events following coronary stent implantation. In such a combination, aspirin inhibits platelet TXA2 generation, and the P2Y12 receptor inhibitor prevents ADP‐induced platelet activation. Aspirin and P2Y12 antagonists are regarded as "agonist‐specific" drugs, selectively inhibiting platelet activation by TXA2 or ADP, respectively. Nonetheless, several studies indicate that these drugs exert antithrombotic effects that are unrelated to inhibition of ADP‐ or TXA2‐induced platelet aggregation.31-33 Recent findings suggest that 12‐hydroxyleicosatetraenoic acid, a procoagulant (tissue factor release) and proaggregatory eicosanoid that is generated alongside TXA2 from arachidonic acid-stimulated platelets, may play a ...
We observed the localization of the contractile proteins myosin, filamentous actin, alpha-actinin, tropomyosin, and vinculin in surface-activated, spreading human platelets using a single fluorescence staining procedure and conventional fluorescence microscopy. Myosin was distributed in a speckled pattern that extended radially from the granulomere. F-actin demonstrated cable-networks. Tropomyosin and alpha-actinin occurred in a punctuate distribution, and vinculin was localized at adhesion sites. Although myosin, F-actin, alpha-actinin, tropomyosin, and vinculin were not studied in resting platelets, our data support the idea that these contractile proteins are reorganized and reassembled in activated platelets during platelet function.
in Circulation (2015), 131(7), 656-68. Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet ... [more ▼]. Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet activation is of importance for the development of improved therapies. Recently, protein tyrosine phosphatases (PTPs) have emerged as critical regulators of platelet function. Methods and Results This is the first report implicating the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human and mouse platelets. ...
Aggregation and adhesion of platelets to the vascular wall are consequences of platelet activation and these cascade processes play critical roles in hemostasis and thrombosis at vascular injury sites. In this study, we designed a simple and rapid assay of platelet aggregation and adhesion in a microfluidic system. To activate platelets, either shear stress or agonists was selectively chosen for the required test. For shear-induced platelet activation (SIPA), a rotating stirrer in a circular chamber was designed with considering shear generation with secondary-flow-induced mixing. Agonists such ADP, epinephrine and arachidonic acid were carefully combined with collagen or fibrinogen. When platelets were activated in whole blood, they were driven through the microchannel under vacuum pressure. Activated ...
Staphylococcus aureus is an opportunistic pathogenic bacterium known for its ability to interact with platelets and modulate their function. S. aureus lipoproteins are one of the major groups of bacterial surface molecules and are released into the extracellular milieu where they are recognized by host immune cells. The aim of this study was to determine the role of S. aureus lipoproteins in S. aureus-platelet interactions. Platelet aggregation and binding assays using S. aureus wild type and lgt strains showed that, S. aureus lipoproteins contribute towards binding of the pathogen to platelets. Lipoproteins present in extracellular milieu also bind platelets. Platelet spreading, thrombus formation, agonist induced platelet aggregation and αIIbβ3 activation were inhibited by ...
Interaction of platelets with collagen under conditions of blood flow is a multistep process with tethering via glycoprotein IbIXV (GPIbIXV) over von Willebrand factor, adhesion by direct interaction with the integrin GPIaIIa, and signaling via GPVI. GPVI can be specifically agonized by cross-linked collagen-related peptide (CRP-XL), which results in a signaling cascade very similar to that evoked by native collagen. The GPVI gene has 2 common alleles that differ by 3 replacements in the glycosylated stem and 2 in the cytoplasmic domain. We used CRP-XL to elucidate the variation in responses observed in platelet function in different individuals. We observed a 3-fold difference in the response to CRP-XL in platelet aggregation when comparing platelets from 10 high-frequency allele homozygotes with 8 low-frequency ones (2-way analysis of variance [ANOVA], P , .0001). The difference in functional responses was ...
Bleeding in J-LANCELOT. Major cardiovascular adverse events with atopaxar were not significantly different from placebo (6.6% placebo versus 5.0% atopaxar, p = 0.73 for ACS, and 4.5% placebo versus 1.0% atopaxar, p = 0.07 for CAD). There was a statistically significant dose-dependent increase in liver function abnormalities and QTc prolongation with atopaxar. At trough levels in both populations, mean inhibition of platelet aggregation was 90% with 100 and 200 mg atopaxar, and 20-60% with 50 mg atopaxar.. Thus, the oral platelet thrombin receptor blocker atopaxar significantly inhibits platelet aggregation in patients with stable and unstable coronary artery disease already on regular antiplatelet therapy, but is associated with increased overall, but not major bleeding in 3 phase-II trials. Also asymptomatic liver enzyme elevation and QT prolongation were observed. Whether this additional class of antiplatelet therapy is ...
ANTICOAGULANTS AND THROMBOLYTIC DRUGSHaemostasisVascular injury results firstly in vasoconstriction and formation of platelet plug at the site of injury (primary haemostasis). The platelet plug is then stabilized by the formation of a fibrin meshwork, resulting from activation of the coagulation cascade.Fibrin is eventually cleared through digestion by fibrinolytic enzymes.Primary HaemostasisWhen endothelial integrity is breached, platelets adhere to exposed subendothelial collagen. The adherent platelets become activated result in;1) Exposure of fibrinogen receptors, allowing fibrinogen to bind and cross-link adjacent platelets. The process is known as platelet aggregation. The platelet fibrinogen receptor consists of a complex of glycoproteins IIb and IIIa on the platelet membrane.2) ...
ABSTRACT. Angiotensin II (Ang II) is a critical component of the renin-angiotensin system that contributes to hypertension. Although platelets in blood from hypertensive subjects have an abnormal biological profile, it is unclear if circulating Ang II influences platelet aggregation or thrombus formation. One of the abnormalities presented to the platelets during hypertension is an elevated plasma concentration of serotonin (5-HT) caused by reduced 5-HT uptake secondary to loss of the 5-HT transporter (SERT) on the platelet plasma membrane. In the current study, we evaluated in vivo platelet function after 7 days of subcutaneous Ang II infusion to establish hypertension in mice and additionally assessed the biology of isolated platelets exposed to Ang II in vitro. The administration of Ang II elevated systolic blood pressure, but markers of ...
Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipid molecules. It inhibits platelet activation and is also an effective vasodilator. When used as a drug, it is also known as epoprostenol. The terms are sometimes used interchangeably. Prostacyclin (PGI2) chiefly prevents formation of the platelet plug involved in primary hemostasis (a part of blood clot formation). It does this by inhibiting platelet activation. It is also an effective vasodilator. Prostacyclins interactions in contrast to thromboxane (TXA2), another eicosanoid, strongly suggest a mechanism of cardiovascular homeostasis between the two hormones in relation to vascular damage. It is used to treat pulmonary artery hypertension. Prostacyclin, which has a half-life of 42 seconds, is broken down into 6-keto-PGF1, which is a much weaker vasodilator. As mentioned above, prostacyclin (PGI2) ...
We have developed a transient computational model of mural thrombogenesis, simulating whole blood flow in real time in a parallel plate flow chamber. Finite element computational methods were utilized to solve governing partial differential equations of mass conservation and fluid flow. The spatial and temporal variation of concentrations of four platelet agonists known to be synthesized by or released from activated platelets (ADP, vWF, thromboxane A$\sb2$ and thrombin) were computed. The embolizing shear, tensile stresses and torque acting on the aggregates due to fluid forces caused by blood flow were also quantitated. The maximum thrombin concentrations (occurring in stagnating fluid pockets proximal to the thrombi) at the end of two minute blood perfusion are more than 800 fold larger compared to those required for irreversible platelet aggregation in vitro (1-3 nM) under all blood flow conditions. While ADP and vWF ...
Angiotensin II (Ang II) is a critical component of the reninangiotensin system that contributes to hypertension. Although platelets in blood from hypertensive subjects have an abnormal biological profile, it is unclear if circulating Ang II influences platelet aggregation or thrombus formation. One of the abnormalities presented to the platelets during hypertension is an elevated plasma concentration of serotonin (5-HT) caused by reduced 5-HT uptake secondary to loss of the 5-HT transporter (SERT) on the platelet plasma membrane. In the current study, we evaluated in vivo platelet function after 7 days of subcutaneous Ang II infusion to establish hypertension in mice and additionally assessed the biology of isolated platelets exposed to Ang II in vitro. The administration of Ang II elevated systolic blood pressure, but markers of ...
Initial platelet activity may predict efficacy after chronic oral glycoprotein IIb/IIIa blockade: should we still consider uniform treatment regimens?
Dosing of mice with clopidogrel (50 mg/kg) completely inhibited ADP-induced ex vivo platelet aggregation and signaling (cAMP) and blocked all of the surface P2Y12 receptors on resting platelets. It is interesting to note that the same high dose of clopidogrel (50 mg/kg) prevented vascular occlusion but did not achieve the thrombotic profile associated with P2Y12 deficiency, whereas the direct-acting inhibitor elinogrel did recapitulate the profile of P2Y12(−/−) mice. Addition of elinogrel (1 mg/kg i.v.) to this clopidogrel regimen (50 mg/kg, 3 days) completely blocked the residual thrombosis, confirming that this process was mediated by P2Y12 receptors. On the basis of this data, we hypothesized that residual thrombosis observed in clopidogrel-treated mice might be due to an unblocked (intracellular) pool of P2Y12 exposed on the platelet surface after platelet activation in vivo. In this ...
The results of the present investigation demonstrate that insulin-stimulated platelets release sufficient amounts of ATP and/or adenosine to relax precontracted porcine coronary arteries. The signaling pathway initiated by insulin involves the activation of platelet eNOS, the soluble guanylyl cyclase and G kinase, and the association of VAMP-3 with the t-SNARE protein, syntaxin 2, and the release of adenine nucleotides and serotonin from dense granules. Since insulin-induced vasodilatation in vivo is sensitive to NOS inhibitors (8) but insulin does not acutely enhance NO production by endothelial cells (20), the NO-dependent release of platelet-derived vasodilator compounds may well account for the phenomenon of insulin-induced vasodilatation in vivo.. The effects of insulin on platelets is controversial since some studies have demonstrated that insulin attenuates ...
Figure 1. ODN2395 binding to platelets and induction of platelet activation, aggregation, and adhesion. (a) ODN2395 was incubated with platelets and binding was assessed (***, P , 0.001 vs. background [BG], 10 µM non-PS-modified ODN2395 ["ODN2395 nonmod"], and 50 nM ODN2395; n = 6). (b) CD62P surface expression after ODN2395 incubation of human washed platelets compared with unstimulated control samples and ODN2395 nonmod (*, P , 0.05 vs. unstimulated/1-10 µM ODN2395 nonmod/50 nM ODN2395; ***, P , 0.001 vs. unstimulated/1-10 µM ODN2395 nonmod/50 nM ODN2395; n = 5). (c) Platelet aggregation after 5 µM ODN2395 stimulation of PRP; final aggregation compared with 5 µM ADP/1 µg/ml collagen stimulation; representative aggregation curves (n = 6). (d) Murine GPIIb/IIIa activation after incubation with ODN2395 (1 µM/5 µM; *, P , 0.05/***, P , 0.001 ...
The polymorphisms C807T end G873A of the platelet integrin alpha2b ta1 collagen receptor glycoprotein GP Ia-IIa are linked to the expression density of this receptor. The GPIa T807/A873 allele causes a higher receptor expression, enhancing platelet binding to collagen. This might present a genetic predisposition for the development of...
Recently, we and others demonstrated that the P2Y1 receptor, necessary for ADP-induced platelet shape change and activation, plays a role in the thromboembolism resulting from intravenous injection of collagen and epinephrine or collagen and ADP.26 27 These in vivo effects could be correlated with the in vitro properties of P2Y1-deficient platelets, which exhibit strongly reduced aggregation in response to ADP or collagen.. In the present study, we investigated the role of the P2Y1 receptor in the acute thrombin-dependent thromboembolism induced by intravenous injection in the jugular vein of thromboplastin. P2Y1-deficient mice were more resistant to thromboplastin-induced thromboembolism than wild-type mice. Mortality, which probably resulted from lung occlusion and cardiac arrest, reflected at least in part the pulmonary vessel occlusion seen on all necropsy specimens. No thrombi were found in the kidneys after thromboplastin injection, ...
New studies in mice suggest that blood platelets can destroy deadly malaria parasites, but a single dose of aspirin may be enough to thwart their killing power., , , , The findings could have important im...
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Recent studies have highlighted the importance of expeditious transfusion of plasma, platelets and red blood cells in a 1:1:1 ratio for severe trauma patients who are at risk of exsanguination. Since thawing plasma can be time-consuming, a recent study published in TRANSFUSION examined the hemostatic properties of thawed and liquid plasma over several days of storage. Briefly, during initial processing after donation 17 pooled ABO-matched plasma units were split into a liquid plasma unit and a frozen unit (subsequently thawed and stored for up to five days), and multiple hemostasis parameters, coagulation factors, and platelet activation assays were performed. A further 119 liquid plasma samples were analyzed for platelet activation and cellular content. Liquid plasma at day seven was comparable to thawed plasma at day five by every assay. However, after 11 days of storage, ...
We studied a broad spectrum of platelet function parameters. Together with a low analytical variability for the various tests, a homogenous group of study subjects, and strictly standardized study conditions, these parameters would give a high sensitivity for detecting effects of infused epinephrine on platelet function.. Platelet count increased progressively with increasing arterial epinephrine in both EDTA- and ACD-anticoagulated blood, and the weight of circulating platelets increased by 29%, indicating recruitment of platelets into the circulation. Platelet size increased significantly in EDTA and decreased in ACD. The difference between EDTA and ACD was significant for both platelet count and size, suggesting that epinephrine not only recruits platelets into the circulation but also induces some microaggregation in ...
The research is a five-year collaboration between University of Bristol researchers Dr Andrew Mumford in the Bristol Heart Institute and Dr Stuart Mundell, Department of Physiology and Pharmacology and Professor Steve Watson and Dr Paul Gissen, University of Birmingham and Dr Martina Daly, University of Sheffield.. Platelets are small cells in the bloodstream that become activated and clump together at areas of injury to prevent excessive bleeding. When this happens in diseased blood vessels, it can cause a heart attack or stroke, which together are the leading cause of death in the western world. Understanding the process of platelet activation better will help scientists to design new anti-platelet drugs that could prevent heart attacks and strokes.. One approach is to study people with rare disorders that stop their platelets from activating properly. These patients can ...
Institute of Immunology, Ministry of Health of the USSR. Research Institute of Biomedical Technology, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR, A. D. Ado.) Translated from Byulleten Éksperimentalnoi Biologii i Meditsiny, Vol. 108, No. 7, pp. 69-71, July, 1989. ...

Localization of the Adhesion Receptor Glycoprotein Ib-IX-V Complex to Lipid Rafts Is Required for Platelet Adhesion and...Localization of the Adhesion Receptor Glycoprotein Ib-IX-V Complex to Lipid Rafts Is Required for Platelet Adhesion and...

Activation of human platelets by the membrane-expressed A1 domain of von Willebrand factor. Blood. ... Platelet activation by von Willebrand factor requires coordinated signaling through thromboxane A2 and Fc γ IIA receptor. J. ... LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation ... Platelet activation by von Willebrand factor requires coordinated signaling through thromboxane A2 and Fc γ IIA receptor. J. ...
more infohttps://rupress.org/jem/article/196/8/1057/39535/Localization-of-the-Adhesion-Receptor-Glycoprotein

Dental Extraction Can Be Performed Safely in Patients on Aspirin Therapy: A Timely ReminderDental Extraction Can Be Performed Safely in Patients on Aspirin Therapy: A Timely Reminder

On activation, phospholipase-A2 acts on the cell membrane to release arachidonic acid. Cyclooxygenase acts on arachidonic acid ... Thromboxane A2 is a potent platelet stimulant leading to degranulation of platelet and platelet aggregation. Aspirin inhibits ... Platelets are small sized, disk-shaped cells without a nucleus. These are derived from bone marrow and released into the ... The activation of platelets, aggregation together, and adherence to the vessel wall is an integral part of physiological ...
more infohttps://www.hindawi.com/journals/isrn/2014/463684/

Thromboxane - WikipediaThromboxane - Wikipedia

... stimulating activation of new platelets as well as increasing platelet aggregation. Platelet aggregation is achieved by ... mediating expression of the glycoprotein complex GP IIb/IIIa in the cell membrane of platelets. Circulating fibrinogen binds ... The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ... Role of A2 in platelet aggregation[edit]. Thromboxane A2 (TXA2), produced by activated platelets, has prothrombotic properties ...
more infohttps://en.wikipedia.org/wiki/Thromboxane_inhibitors

Thromboxane - WikipediaThromboxane - Wikipedia

... stimulating activation of new platelets as well as increasing platelet aggregation.. Platelet aggregation is achieved by ... mediating expression of the glycoprotein complex GP IIb/IIIa in the cell membrane of platelets. Circulating fibrinogen binds ... The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ... Role of A2 in platelet aggregationEdit. Thromboxane A2 (TXA2), produced by activated platelets, has prothrombotic properties, ...
more infohttps://en.m.wikipedia.org/wiki/Thromboxane

Thromboxane : Wikis (The Full Wiki)Thromboxane : Wikis (The Full Wiki)

... stimulating activation of new platelets as well as increasing platelet aggregation.. Platelet aggregation is achieved by ... mediating expression of the glycoprotein complex GP IIb/IIIa in the cell membrane of platelets. Circulating fibrinogen binds ... The mechanism of secretion of thromboxanes from platelets is still unclear.. Role of A2 in platelet aggregation. Thromboxane A2 ... The two major thromboxanes are thromboxane A2 and thromboxane B2.. Thromboxane is named for its role in clot formation ( ...
more infohttp://www.thefullwiki.org/Thromboxane

Thromboxane - WikipediaThromboxane - Wikipedia

... stimulating activation of new platelets as well as increasing platelet aggregation. Platelet aggregation is achieved by ... mediating expression of the glycoprotein complex GP IIb/IIIa in the cell membrane of platelets. Circulating fibrinogen binds ... The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ... Thromboxane is named for its role in clot formation (thrombosis). Thromboxane-A synthase, an enzyme found in platelets, ...
more infohttps://en.wikipedia.org/wiki/Thromboxane

Evaluation of developmental toxicity of guaifenesin using pregnant female rats Shabbir A, Shamsi S, Shahzad M, Butt HI, Aamir K...Evaluation of developmental toxicity of guaifenesin using pregnant female rats Shabbir A, Shamsi S, Shahzad M, Butt HI, Aamir K...

The ADP causes activation of phospholipase C by binding on P2 × 1 receptors present on platelet cell membrane. This leads to ... Aspirin also causes fetal hemorrhage by inhibiting thromboxane A2 production in platelets through inhibition of cyclooxygenase ... ADP acts on platelet receptors and initiates the cascade of events required for normal platelet aggregation process. ADP ... which results in the activation of GpIIb/IIIa complex and leads toward platelet aggregation. The third mechanism includes ...
more infohttp://www.ijp-online.com/article.asp?issn=0253-7613

Thrombin-induced lysosomal exocytosis in human platelets is dependent on secondary activation by ADP and regulated by...Thrombin-induced lysosomal exocytosis in human platelets is dependent on secondary activation by ADP and regulated by...

... and by identifying the fraction of platelets exposing the lysosomal-associated membrane protein (LAMP)-1 on the cell surface by ... We conclude that platelet inhibitors that mimic functional endothelium such as PGI(2) or NO efficiently counteract lysosomal ... while inhibition of thromboxane A(2) formation by treatment with acetylsalicylic acid was of minor importance in this regard. ... Thrombin-induced lysosomal exocytosis in human platelets is dependent on secondary activation by ADP and regulated by ...
more infohttp://oru.diva-portal.org/smash/record.jsf?pid=diva2:906036

Thromboxane A2 - WikipediaThromboxane A2 - Wikipedia

This is achieved by increasing expression of the glycoprotein complex GPIIb/IIIa on the cell membrane of platelets. The same ... it stimulates activation of new platelets as well as increases platelet aggregation. ... Thromboxane A2 (TXA2) is a type of thromboxane that is produced by activated platelets and has prothrombotic properties: ... "Thromboxane A2-induced contraction of rat caudal arterial smooth muscle involves activation of Ca2+ entry and Ca2+sensitization ...
more infohttps://en.wikipedia.org/wiki/Thromboxane_A2

cAMP- and cGMP-elevating agents inhibit GPIbα-mediated aggregation but not GPIbα-stimulated Syk activation in human platelets |...cAMP- and cGMP-elevating agents inhibit GPIbα-mediated aggregation but not GPIbα-stimulated Syk activation in human platelets |...

EB and EM are specific agonists and antagonists, respectively, of GPIbα-mediated Syk activation leading to platelet aggregation ... Our aim was to establish the intracellular signaling response of selective GPIbα activation in human platelets, in particular ... which trigger platelet activation. Despite having an important role, intracellular GPIb-IX-V signaling and its regulation by ... Washed human platelets were incubated with EB, in the presence or absence of echicetin monomers (EM), Src family kinase (SFK) ...
more infohttps://biosignaling.biomedcentral.com/articles/10.1186/s12964-019-0428-1

JCI -
Platelet-RBC interaction mediated by FasL/FasR induces procoagulant activity important for thrombosisJCI - Platelet-RBC interaction mediated by FasL/FasR induces procoagulant activity important for thrombosis

... cell-cell contact between platelets and RBCs mediates PS externalization on the RBC membrane critical for platelet activation ... platelet activation is the release of soluble agonists such as thromboxane and ADP because they increase platelet activation by ... Cell-cell contact between platelets and RBCs is crucial for RBC-platelet interaction. (A) Transmission electron microscopy of ... Cell-cell contact between platelets and RBCs is crucial for RBC-platelet interaction. To determine which signal or mechanism is ...
more infohttps://www.jci.org/articles/view/92077

KAKEN - Research Projects | Action of novel non-receptor type protein-tyrosine kinase, p72^|syk|in immune cells. (KAKENHI...KAKEN - Research Projects | Action of novel non-receptor type protein-tyrosine kinase, p72^|syk|in immune cells. (KAKENHI...

Activation of Syk in platelets is not restricted to thrombin stimulation. Platelet activating factor, thromboxane A2, wheat ... Association with B-cell-antigen receptor with protein-tyrosine kinase p72syk and activation by engagement of membrane IgM. Eur ... Association with B-cell-antigen receptor with protein-tyrosine kinase p72syk and activation by engagement of membrane IgM. Eur ... Association with B-cell-antigen receptor with protein-tyrosine kinase p72syk and activation by engagement of membrane IgM. Eur ...
more infohttps://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05670117/

Chest pain and horsemeat lasagna | ward round stuffChest pain and horsemeat lasagna | ward round stuff

Thromboxane is made from the cell membrane phospholipids of platelets, from a very unsaturated fat called arachadonic acid. The ... is because this drug very effectively inhibits cyclooxygenase enzyme and prevents platelet activation by preventing thromboxane ... If you detect thromboxane or ADP made by your fellow platelets you will go into activation mode at once and join your brave ... The cells therefore dont need so much cholesterol to make the cell membranes nice and stiff and work properly. So the liver is ...
more infohttps://wardroundstuff.com/2013/09/22/chest-pain-and-horsemeat-lasagna/

Mechanisms of electrical vasoconstriction | Journal of NeuroEngineering and Rehabilitation | Full TextMechanisms of electrical vasoconstriction | Journal of NeuroEngineering and Rehabilitation | Full Text

Acute tissue damage was assessed with a membrane permeability (live-dead) fluorescent assay. The Joule heating in tissue was ... Activation pathways were explored by topical application of a specific neural agonist (phenylephrine, alpha-1 receptor), a non- ... "Local platelet activation causes vasoconstriction of large epicardial canine coronary arteries in vivo. Thromboxane A2 and ... from endothelial cells, circulating hormones (i.e. angiotensin II) [9, 10], and damaged platelets [11]. The dominant neural ...
more infohttps://jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-018-0390-y

Platelets and Their DisordersPlatelets and Their Disorders

Platelets play a key role in haemostasis, inflammation and cancer biology ... 2014) Motor‐driven marginal band coiling promotes cell shape change during platelet activation. The Journal of Cell Biology 204 ... 2014) A novel thromboxane A2 receptor N42S variant results in reduced surface expression and platelet dysfunction. Thrombosis ... Hartwig JH and DeSisto M (1991) The cytoskeleton of the resting human blood platelet: structure of the membrane skeleton and ...
more infohttp://www.els.net/WileyCDA/ElsArticle/refId-a0002253.html

Characterization of the cloned HEL cell thromboxane A2 receptor: evidence that the affinity state can be altered by G alpha 13...Characterization of the cloned HEL cell thromboxane A2 receptor: evidence that the affinity state can be altered by G alpha 13...

... induces activation of platelets and vascular smooth muscle contraction via cell surface receptors. A platelet type TXA2 ... decreased the affinity of the receptor for 125I-BOP in COS-7 cell membranes coexpressing HEL-TXR and G alpha 13 to a value ... Characterization of the cloned HEL cell thromboxane A2 receptor: evidence that the affinity state can be altered by G alpha 13 ... Characterization of the cloned HEL cell thromboxane A2 receptor: evidence that the affinity state can be altered by G alpha 13 ...
more infohttp://jpet.aspetjournals.org/content/277/2/1132

Anaphylaxis and Anesthesia:Controversies and New Insights | Anesthesiology | ASA PublicationsAnaphylaxis and Anesthesia:Controversies and New Insights | Anesthesiology | ASA Publications

... thromboxane A2, and platelet-activating factor, are released soon after. Thereafter, mast cells release numerous chemokines and ... An early increase in plasma histamine concentration indicates activation of mast cells and/or basophils and is observed during ... ϵRI receptors located in the plasma membrane of tissue mast cells and blood basophils, whereas lymphocytes, eosinophils, and ... platelets bind IgE antibodies via low-affinity FCϵRII receptors. This initial phase of sensitization is clinically silent. On ...
more infohttp://anesthesiology.pubs.asahq.org/article.aspx?articleid=1932505

Frontiers | Novel Surfaces in Extracorporeal Membrane Oxygenation Circuits | MedicineFrontiers | Novel Surfaces in Extracorporeal Membrane Oxygenation Circuits | Medicine

Platelet inhibition mediated by NO, in both vascular smooth muscle cells and platelets, is primarily cGMP-dependent, requiring ... and an anti-platelet agent with both direct and indirect effects on the platelet that suppress activation and aggregation. NO ... PPC coating of ECC has been shown to have a favorable effect on platelets evidenced by a plateau formation of thromboxane B2 ... Dejana E. Endothelial cell-cell junctions: happy together. Nat Rev Mol Cell Biol. (2004) 5:261-70. doi: 10.1038/nrm1357 ...
more infohttps://www.frontiersin.org/articles/10.3389/fmed.2018.00321/full

Cyclooxygenase-2-Derived Prostacyclin Regulates Arterial Thrombus Formation by Suppressing Tissue Factor in a Sirtuin-1...Cyclooxygenase-2-Derived Prostacyclin Regulates Arterial Thrombus Formation by Suppressing Tissue Factor in a Sirtuin-1...

Role of Platelets in Carotid Artery Thrombosis. Reduction in vascular PGI2 synthesis modulates platelet activation, which is ... may counteract platelet-derived thromboxane (TXA2).5 PGI2 is a potent vasodilator and an inhibitor of platelet aggregation, ... 12 Regulation of TF expression in circulating cells and in cells of the vessel wall involves the activation of a variety of ... transferred to nitrocellulose membrane, and blotted with appropriate antibodies. Anti-tubulin served as a loading control. The ...
more infohttp://circ.ahajournals.org/content/126/11/1373

Thromboembolism in the Cat - WSAVA2005 - VINThromboembolism in the Cat - WSAVA2005 - VIN

The mediators of platelet activation include thrombin, ADP, collagen, and thromboxane A2. Thrombin stimulates platelets to ... Also contributory is the damage to not only the axons but the Schwann cell basement membranes, vessels and endoneurial ... Thromboxane A2 causes vasoconstriction and recruits more platelets to form a clot. The normal endothelial cells around the ... These activated platelets release adenosine diphosphate (ADP) which causes the release of thromboxaneA2 from the platelet ...
more infohttps://www.vin.com/apputil/content/defaultadv1.aspx?pId=11196&meta=Generic&catId=30743&id=3854246&ind=185&objTypeID=17

Frontiers | Molecular Targets of Omega 3 and Conjugated Linoleic Fatty Acids - Micromanaging Cellular Response | PhysiologyFrontiers | Molecular Targets of Omega 3 and Conjugated Linoleic Fatty Acids - "Micromanaging" Cellular Response | Physiology

Saturated fatty acids induce c-Src clustering within membrane subdomains, leading to JNK activation. Cell 147, 173-184. ... The net result is a lower production of pro-thrombotic thromboxanes (TxA2 and TxB2) generated by platelets and of pro- ... effects on platelet functions and redox status in healthy men. FASEB J. 23, 2909-2916. ... unsaturated fatty acids prevent c-Src membrane partitioning and activation, blocking JNK activation. Moreover, Oh et al. (2010) ...
more infohttps://www.frontiersin.org/articles/10.3389/fphys.2012.00042/full

Platelet - WikipediaPlatelet - Wikipedia

Activated platelets have cell membrane projections covering their surface. Platelets are found only in mammals, whereas in ... GPIIb/IIIa activation[edit]. Collagen-mediated GPVI signalling increases the platelet production of thromboxane A2 (TXA2) and ... Platelets secrete thromboxane A2, which acts on the platelets own thromboxane receptors on the platelet surface (hence the so- ... Platelet-coagulation factor interactions: coagulation facilitation[edit]. Platelet activation causes its membrane surface to ...
more infohttps://en.wikipedia.org/wiki/Thrombocytopathy

Human Physiology/Blood physiology - Wikibooks, open books for an open worldHuman Physiology/Blood physiology - Wikibooks, open books for an open world

Platelets, also called thrombocytes, are membrane-bound cell fragments. Platelets have no nucleus, they are between one to two ... Platelets secrete factors that increase local platelet aggregation (e.g., Thromboxane A), enhance vasoconstriction (e.g., ... which contain a variety of substances that stimulate further platelet activation and enhance the hemostatic process. ... Blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). Anatomically ...
more infohttps://en.wikibooks.org/wiki/Human_Physiology/Blood_physiology

IJMS  | Free Full-Text | Understanding Resolvin Signaling Pathways to Improve  Oral Health | HTMLIJMS | Free Full-Text | Understanding Resolvin Signaling Pathways to Improve Oral Health | HTML

These processes are mediated primarily by activation of thromboxane and PG. In human platelet-rich plasma, RvE1 selectively ... This may rupture cell membrane, release of intracellular content and cause tissue damage. The progress of these events results ... with ADP activated platelets may contribute to both resolution of vascular inflammation and ADP-dependent platelet activation [ ... Also, RvD1 enhanced cell migration and cell polarity via PI3K/Akt signaling in Par-C10 cells [92]. These studies indicate that ...
more infohttp://www.mdpi.com/1422-0067/14/3/5501/htm

Hemodynamic disorders and thromboembolic disease  Flashcards by Midean Ismail | BrainscapeHemodynamic disorders and thromboembolic disease Flashcards by Midean Ismail | Brainscape

... which promote platelet adherence and activation. Activation of platelets results in shape change and the release of secretory ... Tissue factor is a membrane-bound procoagulant glycoprotein expressed by subendothelial cells in the vessel wall. Tissue factor ... Activated platelets produce the prostaglandin thromboxane A2 (TXA2), a potent inducer of platelet aggregation. Aspirin inhibits ... Arterial thrombi are rich in platelets, as the processes underlying their development lead to platelet activation. Venous ...
more infohttps://www.brainscape.com/flashcards/hemodynamic-disorders-and-thromboembolic-6843290/packs/10886531
  • They show specific structural elements, including invaginations of the plasma membrane, a network of residual smooth endoplasmic reticulum, a highly specialized cytoskeleton maintaining the discoid structure of platelets and several kinds of organelles. (els.net)
  • Spectrin strands are just beneath the plasma membrane and around the open canalicular system. (els.net)
  • Our aim was to establish the intracellular signaling response of selective GPIbα activation in human platelets, in particular the role of the tyrosine kinase Syk and its regulation by cAMP/PKA and cGMP/PKG pathways, respectively. (biomedcentral.com)
  • Washed human platelets were incubated with EB, in the presence or absence of echicetin monomers (EM), Src family kinase (SFK) inhibitors, Syk inhibitors and the cAMP- and cGMP-elevating agents iloprost and riociguat, respectively. (biomedcentral.com)
  • The primary phase primarily involves the vascular and platelet mediated events that help in early arrest of bleeding as a result of platelet plug formation. (hindawi.com)
  • The pathological basis related to arterial thrombosis involves atherosclerotic vascular disease mediated by platelet thrombi. (hindawi.com)
  • 3) megakaryocyte extends proplatelets, through continuous actin‐dependent branching, and (4) after a retraction, proplatelets are released from the cell body into vascular sinusoids, (5) where they interconvert into preplatelets and (6) preplatelets undergo further fragmentation to yield individual platelets. (els.net)
  • causes include low platelet count, defective platelet function, and loss of vascular wall support, as in vitamin C deficiency. (brainscape.com)
  • If the cap of a vulnerable plaque erodes or ruptures, as in myocardial infarction , platelets stick to the damaged lining of the vessel and to each other within seconds and form a plug. (wikipedia.org)
  • Exocytosis of lysosomal contents from platelets has been speculated to participate in clearance of thrombi and vessel wall remodelling. (diva-portal.org)
  • Sol-gel zone - is rich in microtubules and microfilaments, allowing the platelets to maintain their discoid shape. (wikipedia.org)
  • 2008) Inherited human cPLA(2alpha) deficiency is associated with impaired eicosanoid biosynthesis, small intestinal ulceration, and platelet dysfunction. (els.net)
  • It has been reported that cats have inherently higher platelet reactivity and that their platelets are larger with greater storage for agonists. (vin.com)
  • EB-induced platelet aggregation was dependent on integrin α IIb β 3 and secondary mediators ADP and TxA 2 , and was antagonized by EM. (biomedcentral.com)
  • The clinical manifestations are the consequences of the immediate as well as ongoing release of preformed mediators from mast cells and basophils. (asahq.org)
  • Acute tissue damage was assessed with a membrane permeability (live-dead) fluorescent assay. (biomedcentral.com)
  • The platelets congregate around the wound in order to create a cap to stop blood flow out of the tissue. (wikipedia.org)
  • In long-standing chronic congestion, hypoxia may lead to parenchymal cell death and secondary tissue fibrosis, and the elevated intravascular pressure may cause edema. (brainscape.com)
  • Carbon dioxide is produced by cells as they undergo the processes of cellular respiration (particularly the Kreb's Cycle). (wikibooks.org)
  • Formed cellular elements (red and white blood cells, and platelets) which combine to make the remaining 45% of blood volume. (wikibooks.org)
  • Pathologically, platelet hypofunction and hyperfunction can result in life-threatening bleeding or thromboinflammatory disorders, respectively. (biomedcentral.com)
  • Defects in these complex signalling networks determine inherited or acquired platelet disorders, mainly characterized by altered haemostasis. (els.net)
  • The identification of specific sub‐network defects in inherited platelet disorders will allow better classification of platelet‐related diseases. (els.net)
  • and Department of Cell and Developmental Biology (L.R.H.) and Division of Hematology-Medical Oncology (B.B.W.), Weill Cornell Medical College, New York, NY. (ahajournals.org)